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Les infections urinaires, Quelle prise en charge en 2017 ? Gestion des BMR : Nouvelles problématiques et « vieux » antibiotiques Aix en Provence 9 mars 2017 H. Chardon Centre Hospitalier du Pays d’Aix Aix en Provence

Les infections urinaires, Quelle prise en charge en 2017 BMR.pdf · Associations céphalosporine(s) ... 1950 : synthèse 4 diastéréoisomères Seul D-thréo est antibiotique F Florfénicol

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Les infections urinaires Quelle prise en charge en 2017

Gestion des BMR

Nouvelles probleacutematiques et laquo vieux raquo antibiotiques

Aix en Provence 9 mars 2017

H Chardon

Centre Hospitalier du Pays drsquoAix Aix en Provence

Laboratoires SANOFI

Staphylococcus aureus reacutesistant agrave la Meacuteticilline (SARM) Staphylococcus aureus reacutesistant agrave la vancomycine ou teicoplanine Enteacuterobacteacuterie productrice de BLSE (Becircta Lactamase agrave Spectre Elargi) Enteacuterobacteacuterie hyperproductrice de ceacutephalosporinase et non

productrice de BLSE en neacuteonatologie Enteacuterobacteacuterie hyperproductrice de ceacutephalosporinase plasmidiques et

non productrice de BLSE Enterobacteacuterie reacutesistante ou intermeacutediaire agrave limipeacutenegraveme Pseudomonas aeruginosa intermeacutediaire etou reacutesistant agrave la ceftazidime

et agrave limipeacutenegraveme Enteacuterocoque reacutesistant agrave la vancomycine Acinetobacter baumannii intermeacutediaire ou reacutesistant agrave limipeacutenegraveme Acinetobacter baumannii reacutesistant agrave toutes les beacutetalactamines sauf

imipeacutenegraveme Burkholderia cepacia quelque soit lantibiogramme Stenotrophomonas maltophilia quelque soit lantibiogramme

EPC E faecium reacutesistant vancomycine Enteacuterobacteacuterie avec reacutesistance plasmidique agrave

la colistine

PDR pandrug resistance reacutesistant agrave toutes les familles drsquoantibiotiques XDR extensively extreme drug resistance reacutesistant agrave toutes les familles drsquoantibiotiques sauf 1 ou 2 MDR multidrug resistance resistant agrave au moins 3 familles drsquoantibiotiques

Magiorakos CMI 2012

OMS - Communiqueacute de presse - 27 FEacuteVRIER 2017 - GENEgraveVE (mis en forme par lrsquoAFP)

Le nombre de BMR augmente Les BMR tuent

De plus en plus

E coli et C3G EARS-Net European Antimicrobial Resistance Surveillance Network

2005

France 2

2015

11

2014

EARS-Net

K pneumoniae et C3G

2005

France 4

EARS-Net

2015

305

EARS-Net

N BLSE

2026 eacutepisodes au total

2009 10 2010 28 2011 113 2012 233 2013 401 2014 650 2015 582

Santeacute Publique France

Nombre drsquoeacutepisodes drsquoEPC 2012 ndash 2015 par deacutepartement

Taille des eacutepisodes les plus importants (N = 187)

Bilan au 4 septembre 2015 (N= 1 866 eacutepisodes)

Lrsquoanalyse par taille preacutesente uniquement les eacutepisodes les plus importants (ge 15 cas) avec une eacutevolution reacutecente (nouveaux cas lt 6 mois)

Santeacute Publique France

Proportion de deacutecegraves

attribuables ()

2016 - THE REVIEW ON ANTIMICROBIAL RESISTANCE - JIM OrsquoNEILL

DEATHS ATTRIBUTABLE TO AMR EVERY YEAR

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Laboratoires SANOFI

Staphylococcus aureus reacutesistant agrave la Meacuteticilline (SARM) Staphylococcus aureus reacutesistant agrave la vancomycine ou teicoplanine Enteacuterobacteacuterie productrice de BLSE (Becircta Lactamase agrave Spectre Elargi) Enteacuterobacteacuterie hyperproductrice de ceacutephalosporinase et non

productrice de BLSE en neacuteonatologie Enteacuterobacteacuterie hyperproductrice de ceacutephalosporinase plasmidiques et

non productrice de BLSE Enterobacteacuterie reacutesistante ou intermeacutediaire agrave limipeacutenegraveme Pseudomonas aeruginosa intermeacutediaire etou reacutesistant agrave la ceftazidime

et agrave limipeacutenegraveme Enteacuterocoque reacutesistant agrave la vancomycine Acinetobacter baumannii intermeacutediaire ou reacutesistant agrave limipeacutenegraveme Acinetobacter baumannii reacutesistant agrave toutes les beacutetalactamines sauf

imipeacutenegraveme Burkholderia cepacia quelque soit lantibiogramme Stenotrophomonas maltophilia quelque soit lantibiogramme

EPC E faecium reacutesistant vancomycine Enteacuterobacteacuterie avec reacutesistance plasmidique agrave

la colistine

PDR pandrug resistance reacutesistant agrave toutes les familles drsquoantibiotiques XDR extensively extreme drug resistance reacutesistant agrave toutes les familles drsquoantibiotiques sauf 1 ou 2 MDR multidrug resistance resistant agrave au moins 3 familles drsquoantibiotiques

Magiorakos CMI 2012

OMS - Communiqueacute de presse - 27 FEacuteVRIER 2017 - GENEgraveVE (mis en forme par lrsquoAFP)

Le nombre de BMR augmente Les BMR tuent

De plus en plus

E coli et C3G EARS-Net European Antimicrobial Resistance Surveillance Network

2005

France 2

2015

11

2014

EARS-Net

K pneumoniae et C3G

2005

France 4

EARS-Net

2015

305

EARS-Net

N BLSE

2026 eacutepisodes au total

2009 10 2010 28 2011 113 2012 233 2013 401 2014 650 2015 582

Santeacute Publique France

Nombre drsquoeacutepisodes drsquoEPC 2012 ndash 2015 par deacutepartement

Taille des eacutepisodes les plus importants (N = 187)

Bilan au 4 septembre 2015 (N= 1 866 eacutepisodes)

Lrsquoanalyse par taille preacutesente uniquement les eacutepisodes les plus importants (ge 15 cas) avec une eacutevolution reacutecente (nouveaux cas lt 6 mois)

Santeacute Publique France

Proportion de deacutecegraves

attribuables ()

2016 - THE REVIEW ON ANTIMICROBIAL RESISTANCE - JIM OrsquoNEILL

DEATHS ATTRIBUTABLE TO AMR EVERY YEAR

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Staphylococcus aureus reacutesistant agrave la Meacuteticilline (SARM) Staphylococcus aureus reacutesistant agrave la vancomycine ou teicoplanine Enteacuterobacteacuterie productrice de BLSE (Becircta Lactamase agrave Spectre Elargi) Enteacuterobacteacuterie hyperproductrice de ceacutephalosporinase et non

productrice de BLSE en neacuteonatologie Enteacuterobacteacuterie hyperproductrice de ceacutephalosporinase plasmidiques et

non productrice de BLSE Enterobacteacuterie reacutesistante ou intermeacutediaire agrave limipeacutenegraveme Pseudomonas aeruginosa intermeacutediaire etou reacutesistant agrave la ceftazidime

et agrave limipeacutenegraveme Enteacuterocoque reacutesistant agrave la vancomycine Acinetobacter baumannii intermeacutediaire ou reacutesistant agrave limipeacutenegraveme Acinetobacter baumannii reacutesistant agrave toutes les beacutetalactamines sauf

imipeacutenegraveme Burkholderia cepacia quelque soit lantibiogramme Stenotrophomonas maltophilia quelque soit lantibiogramme

EPC E faecium reacutesistant vancomycine Enteacuterobacteacuterie avec reacutesistance plasmidique agrave

la colistine

PDR pandrug resistance reacutesistant agrave toutes les familles drsquoantibiotiques XDR extensively extreme drug resistance reacutesistant agrave toutes les familles drsquoantibiotiques sauf 1 ou 2 MDR multidrug resistance resistant agrave au moins 3 familles drsquoantibiotiques

Magiorakos CMI 2012

OMS - Communiqueacute de presse - 27 FEacuteVRIER 2017 - GENEgraveVE (mis en forme par lrsquoAFP)

Le nombre de BMR augmente Les BMR tuent

De plus en plus

E coli et C3G EARS-Net European Antimicrobial Resistance Surveillance Network

2005

France 2

2015

11

2014

EARS-Net

K pneumoniae et C3G

2005

France 4

EARS-Net

2015

305

EARS-Net

N BLSE

2026 eacutepisodes au total

2009 10 2010 28 2011 113 2012 233 2013 401 2014 650 2015 582

Santeacute Publique France

Nombre drsquoeacutepisodes drsquoEPC 2012 ndash 2015 par deacutepartement

Taille des eacutepisodes les plus importants (N = 187)

Bilan au 4 septembre 2015 (N= 1 866 eacutepisodes)

Lrsquoanalyse par taille preacutesente uniquement les eacutepisodes les plus importants (ge 15 cas) avec une eacutevolution reacutecente (nouveaux cas lt 6 mois)

Santeacute Publique France

Proportion de deacutecegraves

attribuables ()

2016 - THE REVIEW ON ANTIMICROBIAL RESISTANCE - JIM OrsquoNEILL

DEATHS ATTRIBUTABLE TO AMR EVERY YEAR

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

EPC E faecium reacutesistant vancomycine Enteacuterobacteacuterie avec reacutesistance plasmidique agrave

la colistine

PDR pandrug resistance reacutesistant agrave toutes les familles drsquoantibiotiques XDR extensively extreme drug resistance reacutesistant agrave toutes les familles drsquoantibiotiques sauf 1 ou 2 MDR multidrug resistance resistant agrave au moins 3 familles drsquoantibiotiques

Magiorakos CMI 2012

OMS - Communiqueacute de presse - 27 FEacuteVRIER 2017 - GENEgraveVE (mis en forme par lrsquoAFP)

Le nombre de BMR augmente Les BMR tuent

De plus en plus

E coli et C3G EARS-Net European Antimicrobial Resistance Surveillance Network

2005

France 2

2015

11

2014

EARS-Net

K pneumoniae et C3G

2005

France 4

EARS-Net

2015

305

EARS-Net

N BLSE

2026 eacutepisodes au total

2009 10 2010 28 2011 113 2012 233 2013 401 2014 650 2015 582

Santeacute Publique France

Nombre drsquoeacutepisodes drsquoEPC 2012 ndash 2015 par deacutepartement

Taille des eacutepisodes les plus importants (N = 187)

Bilan au 4 septembre 2015 (N= 1 866 eacutepisodes)

Lrsquoanalyse par taille preacutesente uniquement les eacutepisodes les plus importants (ge 15 cas) avec une eacutevolution reacutecente (nouveaux cas lt 6 mois)

Santeacute Publique France

Proportion de deacutecegraves

attribuables ()

2016 - THE REVIEW ON ANTIMICROBIAL RESISTANCE - JIM OrsquoNEILL

DEATHS ATTRIBUTABLE TO AMR EVERY YEAR

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

PDR pandrug resistance reacutesistant agrave toutes les familles drsquoantibiotiques XDR extensively extreme drug resistance reacutesistant agrave toutes les familles drsquoantibiotiques sauf 1 ou 2 MDR multidrug resistance resistant agrave au moins 3 familles drsquoantibiotiques

Magiorakos CMI 2012

OMS - Communiqueacute de presse - 27 FEacuteVRIER 2017 - GENEgraveVE (mis en forme par lrsquoAFP)

Le nombre de BMR augmente Les BMR tuent

De plus en plus

E coli et C3G EARS-Net European Antimicrobial Resistance Surveillance Network

2005

France 2

2015

11

2014

EARS-Net

K pneumoniae et C3G

2005

France 4

EARS-Net

2015

305

EARS-Net

N BLSE

2026 eacutepisodes au total

2009 10 2010 28 2011 113 2012 233 2013 401 2014 650 2015 582

Santeacute Publique France

Nombre drsquoeacutepisodes drsquoEPC 2012 ndash 2015 par deacutepartement

Taille des eacutepisodes les plus importants (N = 187)

Bilan au 4 septembre 2015 (N= 1 866 eacutepisodes)

Lrsquoanalyse par taille preacutesente uniquement les eacutepisodes les plus importants (ge 15 cas) avec une eacutevolution reacutecente (nouveaux cas lt 6 mois)

Santeacute Publique France

Proportion de deacutecegraves

attribuables ()

2016 - THE REVIEW ON ANTIMICROBIAL RESISTANCE - JIM OrsquoNEILL

DEATHS ATTRIBUTABLE TO AMR EVERY YEAR

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

OMS - Communiqueacute de presse - 27 FEacuteVRIER 2017 - GENEgraveVE (mis en forme par lrsquoAFP)

Le nombre de BMR augmente Les BMR tuent

De plus en plus

E coli et C3G EARS-Net European Antimicrobial Resistance Surveillance Network

2005

France 2

2015

11

2014

EARS-Net

K pneumoniae et C3G

2005

France 4

EARS-Net

2015

305

EARS-Net

N BLSE

2026 eacutepisodes au total

2009 10 2010 28 2011 113 2012 233 2013 401 2014 650 2015 582

Santeacute Publique France

Nombre drsquoeacutepisodes drsquoEPC 2012 ndash 2015 par deacutepartement

Taille des eacutepisodes les plus importants (N = 187)

Bilan au 4 septembre 2015 (N= 1 866 eacutepisodes)

Lrsquoanalyse par taille preacutesente uniquement les eacutepisodes les plus importants (ge 15 cas) avec une eacutevolution reacutecente (nouveaux cas lt 6 mois)

Santeacute Publique France

Proportion de deacutecegraves

attribuables ()

2016 - THE REVIEW ON ANTIMICROBIAL RESISTANCE - JIM OrsquoNEILL

DEATHS ATTRIBUTABLE TO AMR EVERY YEAR

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Le nombre de BMR augmente Les BMR tuent

De plus en plus

E coli et C3G EARS-Net European Antimicrobial Resistance Surveillance Network

2005

France 2

2015

11

2014

EARS-Net

K pneumoniae et C3G

2005

France 4

EARS-Net

2015

305

EARS-Net

N BLSE

2026 eacutepisodes au total

2009 10 2010 28 2011 113 2012 233 2013 401 2014 650 2015 582

Santeacute Publique France

Nombre drsquoeacutepisodes drsquoEPC 2012 ndash 2015 par deacutepartement

Taille des eacutepisodes les plus importants (N = 187)

Bilan au 4 septembre 2015 (N= 1 866 eacutepisodes)

Lrsquoanalyse par taille preacutesente uniquement les eacutepisodes les plus importants (ge 15 cas) avec une eacutevolution reacutecente (nouveaux cas lt 6 mois)

Santeacute Publique France

Proportion de deacutecegraves

attribuables ()

2016 - THE REVIEW ON ANTIMICROBIAL RESISTANCE - JIM OrsquoNEILL

DEATHS ATTRIBUTABLE TO AMR EVERY YEAR

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

E coli et C3G EARS-Net European Antimicrobial Resistance Surveillance Network

2005

France 2

2015

11

2014

EARS-Net

K pneumoniae et C3G

2005

France 4

EARS-Net

2015

305

EARS-Net

N BLSE

2026 eacutepisodes au total

2009 10 2010 28 2011 113 2012 233 2013 401 2014 650 2015 582

Santeacute Publique France

Nombre drsquoeacutepisodes drsquoEPC 2012 ndash 2015 par deacutepartement

Taille des eacutepisodes les plus importants (N = 187)

Bilan au 4 septembre 2015 (N= 1 866 eacutepisodes)

Lrsquoanalyse par taille preacutesente uniquement les eacutepisodes les plus importants (ge 15 cas) avec une eacutevolution reacutecente (nouveaux cas lt 6 mois)

Santeacute Publique France

Proportion de deacutecegraves

attribuables ()

2016 - THE REVIEW ON ANTIMICROBIAL RESISTANCE - JIM OrsquoNEILL

DEATHS ATTRIBUTABLE TO AMR EVERY YEAR

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

EARS-Net

K pneumoniae et C3G

2005

France 4

EARS-Net

2015

305

EARS-Net

N BLSE

2026 eacutepisodes au total

2009 10 2010 28 2011 113 2012 233 2013 401 2014 650 2015 582

Santeacute Publique France

Nombre drsquoeacutepisodes drsquoEPC 2012 ndash 2015 par deacutepartement

Taille des eacutepisodes les plus importants (N = 187)

Bilan au 4 septembre 2015 (N= 1 866 eacutepisodes)

Lrsquoanalyse par taille preacutesente uniquement les eacutepisodes les plus importants (ge 15 cas) avec une eacutevolution reacutecente (nouveaux cas lt 6 mois)

Santeacute Publique France

Proportion de deacutecegraves

attribuables ()

2016 - THE REVIEW ON ANTIMICROBIAL RESISTANCE - JIM OrsquoNEILL

DEATHS ATTRIBUTABLE TO AMR EVERY YEAR

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

K pneumoniae et C3G

2005

France 4

EARS-Net

2015

305

EARS-Net

N BLSE

2026 eacutepisodes au total

2009 10 2010 28 2011 113 2012 233 2013 401 2014 650 2015 582

Santeacute Publique France

Nombre drsquoeacutepisodes drsquoEPC 2012 ndash 2015 par deacutepartement

Taille des eacutepisodes les plus importants (N = 187)

Bilan au 4 septembre 2015 (N= 1 866 eacutepisodes)

Lrsquoanalyse par taille preacutesente uniquement les eacutepisodes les plus importants (ge 15 cas) avec une eacutevolution reacutecente (nouveaux cas lt 6 mois)

Santeacute Publique France

Proportion de deacutecegraves

attribuables ()

2016 - THE REVIEW ON ANTIMICROBIAL RESISTANCE - JIM OrsquoNEILL

DEATHS ATTRIBUTABLE TO AMR EVERY YEAR

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

EARS-Net

N BLSE

2026 eacutepisodes au total

2009 10 2010 28 2011 113 2012 233 2013 401 2014 650 2015 582

Santeacute Publique France

Nombre drsquoeacutepisodes drsquoEPC 2012 ndash 2015 par deacutepartement

Taille des eacutepisodes les plus importants (N = 187)

Bilan au 4 septembre 2015 (N= 1 866 eacutepisodes)

Lrsquoanalyse par taille preacutesente uniquement les eacutepisodes les plus importants (ge 15 cas) avec une eacutevolution reacutecente (nouveaux cas lt 6 mois)

Santeacute Publique France

Proportion de deacutecegraves

attribuables ()

2016 - THE REVIEW ON ANTIMICROBIAL RESISTANCE - JIM OrsquoNEILL

DEATHS ATTRIBUTABLE TO AMR EVERY YEAR

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

N BLSE

2026 eacutepisodes au total

2009 10 2010 28 2011 113 2012 233 2013 401 2014 650 2015 582

Santeacute Publique France

Nombre drsquoeacutepisodes drsquoEPC 2012 ndash 2015 par deacutepartement

Taille des eacutepisodes les plus importants (N = 187)

Bilan au 4 septembre 2015 (N= 1 866 eacutepisodes)

Lrsquoanalyse par taille preacutesente uniquement les eacutepisodes les plus importants (ge 15 cas) avec une eacutevolution reacutecente (nouveaux cas lt 6 mois)

Santeacute Publique France

Proportion de deacutecegraves

attribuables ()

2016 - THE REVIEW ON ANTIMICROBIAL RESISTANCE - JIM OrsquoNEILL

DEATHS ATTRIBUTABLE TO AMR EVERY YEAR

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

2026 eacutepisodes au total

2009 10 2010 28 2011 113 2012 233 2013 401 2014 650 2015 582

Santeacute Publique France

Nombre drsquoeacutepisodes drsquoEPC 2012 ndash 2015 par deacutepartement

Taille des eacutepisodes les plus importants (N = 187)

Bilan au 4 septembre 2015 (N= 1 866 eacutepisodes)

Lrsquoanalyse par taille preacutesente uniquement les eacutepisodes les plus importants (ge 15 cas) avec une eacutevolution reacutecente (nouveaux cas lt 6 mois)

Santeacute Publique France

Proportion de deacutecegraves

attribuables ()

2016 - THE REVIEW ON ANTIMICROBIAL RESISTANCE - JIM OrsquoNEILL

DEATHS ATTRIBUTABLE TO AMR EVERY YEAR

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Nombre drsquoeacutepisodes drsquoEPC 2012 ndash 2015 par deacutepartement

Taille des eacutepisodes les plus importants (N = 187)

Bilan au 4 septembre 2015 (N= 1 866 eacutepisodes)

Lrsquoanalyse par taille preacutesente uniquement les eacutepisodes les plus importants (ge 15 cas) avec une eacutevolution reacutecente (nouveaux cas lt 6 mois)

Santeacute Publique France

Proportion de deacutecegraves

attribuables ()

2016 - THE REVIEW ON ANTIMICROBIAL RESISTANCE - JIM OrsquoNEILL

DEATHS ATTRIBUTABLE TO AMR EVERY YEAR

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Proportion de deacutecegraves

attribuables ()

2016 - THE REVIEW ON ANTIMICROBIAL RESISTANCE - JIM OrsquoNEILL

DEATHS ATTRIBUTABLE TO AMR EVERY YEAR

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

2016 - THE REVIEW ON ANTIMICROBIAL RESISTANCE - JIM OrsquoNEILL

DEATHS ATTRIBUTABLE TO AMR EVERY YEAR

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

EARS-Net

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

K pneumoniae820 NET GM TM AN NA CIP OFX LVX SXT

Nb 397 819 670 807 656 816 706 228 766

S 308 687 521 764 452 626 497 200 564

I 14 7 11 14 47 35 24 8 5

R 75 125 138 29 157 155 185 20 197

S 7758 8388 7776 9467 6890 7672 7040 8772 7363

I 353 085 164 173 716 429 340 351 065

R 1889 1526 2060 359 2393 1900 2620 877 2572

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Aztreacuteonam surhelliples carbapeacutenegravemases

(meacutetallo-enzymes)

Nordmann et al Clin Microbiol Infect 2002

Associations ceacutephalosporine(s) hellip + inhibiteur de beacutetalactamases Les pistes qui semblent devoir ecirctre exploreacutees en France sont celles de lrsquoassociation drsquoune C3G et tout particuliegraverement la ceftazidime avec lrsquoacide clavulanique (quitte agrave utiliser lrsquoassociation amoxicilline + acide clavulanique pour disposer drsquoacide clavulanique)

HCSP - 2010

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

CASFM 2016 et EUCAST 2017

CASFM 2017

PSEUDOMONAS

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Les nouveaux inhibiteurs de becircta-lactamase Inhibiteurs de BLSE

NXL 104 - AVIBACTAM

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Lagaceacute-Wiens AAC 2011

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Lagaceacute-Wiens AAC 2011

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

CMI mgL CMI 50 CMI 90 S Ceftazidime ge512 ge512 0 + NXL 104 4 microgL 0125 05 100 2 2 8 100 1 8 8 90 Endimiani AAC 2009

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Sensibiliteacute CAZ CAZ + avib

CEFTAZIDIME ndash AVIBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste compleacutementaire Pseudomonas CASFM 2017

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Sensibiliteacute CAZ CT

CT CEFTOLOZANE ndash TAZOBACTAM Pyo R meacuteropeacutenegraveme BLR Pyo R pipeacuteracilline-tazobactam ceacutefeacutepime meacuteropeacutenegraveme et imipeacutenegraveme Enteacuterobacteacuteries R ceacutefeacutepime CRE K pneumoniae carbapeacutenegraveme-reacutesistant

Gonzalez Ann Lab Med 2017

Liste standard Pseudomonas CASFM 2017

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Neuner AAC 2012 Sensibiliteacute globale 86

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Neuner AAC 2012

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

CH Aix en Provence Disques I2a CASFM 2016 Disque 200 microg

EUCAST 2017 Charge du disque 200 microg

S le 64 mgL R gt 128 mgL (drsquoapregraves CLSI)

S le 32 mgL R gt 32 mgL

Diminution de concentration critique de 64 agrave 32 mgL Augmentation de 8 mm (16 agrave 24 mm) pour une seule dilution N de E coli reacutesistants agrave fosfomycine

Fosfomycine ndash CASFM 2017

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Le gegravene correspondant mcr-1 code une

phosphoeacutethanolamine transfeacuterase plasmidique

qui confegravere un bas niveau de reacutesistance agrave la

colistine (CMI modale 4 microgmL)

Colistine

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Liu YY Wang Y Walsh TR Yi LX Zhang R Spencer J et al

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study

Lancet Infect Dis 2016

The recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A which reduces the LPS anionic charge and subsequently its affinity to the cationic colistin

Colistine

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Mars 2016

Colistine

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Animal Aliment et Environnement Homme

Eurosurveillance Mars 2016

Colistine

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Cassir Frontiers in Microbiology 2014

Infections caused by multidrug-resistant Gram-negative bacteria successfully treated with old antibiotics

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Reference testing of Enterobacteriaceae Pseudomonas aeruginosa and Acinetobacter spp is by the ISO-standard broth microdilution method (20776-1) a Cation-adjusted Mueller-Hinton Broth is used b No additives may be included in any part of the testing process (in particular no polysorbate-80 or other surfactants) c Trays must be made of plain polystyrene and not treated in any way before use d Sulphate salts of polymyxins must be used (the methanesulfonate derivative of colistin must not be used - it is an inactive pro-drug that breaks down slowly in solution) Susceptibility testing by other methods including agar dilution disk diffusion and gradient diffusion cannot be recommended until historical data have been reviewed or new study data have been generated Work on these methods is ongoing Published on wwweucastorg 22 March 2016

Colistine

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Biocentricreg France

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Dafopoulou AAC 2015

Le gegravene correspondant mcr-1 code une phosphoeacutethanolamine transfeacuterase plasmidique qui confegravere un bas niveau de reacutesistance agrave la colistine (CMI modale 4 microgmL)

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Dafopoulou AAC 2015

HAS laquo Agrave ce jour nous disposons drsquoun recul limiteacute sur les performances du deacutepistage de ces enteacuterobacteacuteries agrave lrsquoaide des meacutethodes automatiseacutees drsquoantibiogramme en milieu liquide raquo

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Thiampheacutenicol

1949 Streptomyces venezuelae 1950 synthegravese 4 diasteacutereacuteoisomegraveres Seul D-threacuteo est antibiotique

F

Florfeacutenicol

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Civljak

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

483 (75) MDR-GNB strains were obtained from 650 consecutive GNB isolated in the Microbiology lab during the six months study period ( resistance to at least three of the different classes of commonly used antimicrobials (Penicillins Cephalosporins Aminoglycosides Flouroquinolones β lactamsβ lactamase inhibitor combinations and Carbapenems)

Smita Sood Journal of Clinical and Diagnostic Research 2016

68 of the MDR GNB isolates were found to be sensitive to chloramphenicol

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Infections caused by multidrug-resistant Gram-positive bacteria successfully treated with old antibiotics

Cassir Frontiers in Microbiology 2014

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Successful treatment of recurrent and complicated urinary tract infection in an immunocompromised patient caused by carbapenem- and colistin-resistant Klebsiella pneumoniae with the association of chloramphenicol and ertapenem

Silvia Figueiredo Costa ECCMID 2016 P6385

Chlorampheacutenicol

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

S le R gt Enteacuterobacteacuteries 8 8 Burkholderia cepacia 8 16 Staphylococcus 8 8 Enterococcus 8 16 Pneumocoque 8 8 Streptocoque heacutemolytique 8 8 Autres streptocoques 8 8 Haemophilus 2 2 Moraxella 2 2 Interpreacutetation valable pour le thiampheacutenicol Remarque preacutesente degraves le communiqueacute depuis toujours et dans le livre laquo Lrsquoantibiogramme raquo Thiampheacutenicol nrsquoest jamais citeacute dans le communiqueacute EUCAST Nrsquoest jamais citeacute dans CLSI

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

0

2000

4000

6000

8000

10000

12000

14000

16000

0032 0064 0125 025 05 1 2 4 8 16 32 64 128

Chlorampheacutenicol

Neisseria meningitidis Haemophilus influenzae

Streptococcus pneumoniae

ECOFF 2 2 8

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

0

1000

2000

3000

4000

5000

6000

05 1 2 4 8 16 32 64 128 256 512

Escherichia coli (EUCAST)

0

5

10

15

20

25

30

05 1 2 4 8 16 32 64 128 256 512

Klebsiella pneumoniae (EUCAST)

CMI Chlorampheacutenicol

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Tableau 2 CMI du chlorampheacutenicol du thiampheacutenicol et du florfeacutenicol vis-agrave-vis de

Escherichia coli et de Staphylococcus aureus selon le meacutecanisme de reacutesistance

Organisme Meacutecanisme de

reacutesistancea CMI (mgL)

Chlorampheacutenicol Thiampheacutenicol Florfeacutenicol E coli sauvage

impermeacuteabiliteacute mutation ribosomale CAT type I CAT type II CAT type III

2 32 32 256 256 512

32 128 512

1024 512

1024

4 32 32 4 4 8

S aureus sauvage CAT cfr

4 64 64

8 512 -

b

2 2

32 a CAT Chlorampheacutenicol aceacutetyltransfeacuterase

b - non deacutetermineacute

laquo Le thiampheacutenicol preacutesente un spectre tregraves large comparable agrave celui du chlorampheacutenicol mais possegravede une activiteacute intrinseacuteque moins importante que ce dernier raquo in laquo Antibiogramme raquo ESKA 3egraveme eacutedition

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

The antibacterial activity of thiamphenicol was compared to that of chloramphenicol against 313 strains of gram-negative bacilli isolated from various clinical specimens These two antiboitics were equally active against the 106 isolates of Haemophilus MIC equals

01 minus 156 mu gml) and against 40 strains of Bacteroides fragilis (almost all strains being inhibited by 125 mugml of the two drugs)

In contrast when compared with chloramphenicol 2-16 times as much of thiamphenicol was required to inhibit Enterobacteriacae making prediction of the susceptibility of these strains to thiamphenicol on the basis of chloramphenicol testing alone likely to be hazardous

Beers DV Chemotherapy 197521(2)73-81

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association

Outcomes of patients infected with carbapenemase-producing Klebsiella pneumoniae according to treatment regimen Regimen A inappropriate therapy (no drug was active in vitro) Regimen B monotherapy (one drug was active in vitro) Regimen C combination therapy (two or more drugs were active in vitro) Regimen C1 combination therapy with two or more in vitro-active drugs not including a carbapenem Regimen C2 combination therapy with two or more in vitro-active drugs one of which was a carbapenem Tzouvelekis CMI 2014

hellip et les autres bull Tygeacutecycline bull Teacutemocilline bull Minocycline bull Cotrimoxazole bull Rifampicine bull etchellip hellip en association