interpretation of esbl and carbapenemase phenotypes · 6 β-lactamases class c = ampc yvonne...

1

Interpretation of ESBL and

carbapenemase phenotypes

Yvonne Pfeifer FG13 Nosocomial Pathogens and Antibiotic Resistance

Robert Koch Institute Wernigerode Germany

EURL-AR Training Course Copenhagen 24th-26th of September 2014

Yvonne Pfeifer 2

Robert Koch Institute Wernigerode

National Reference Center Staphylococci (MRSA) and Enterococci

Department 11 Bacterial Enteric Pathogens and Legionella

National Reference Center Salmonella and other Enteric Pathogens

Department 13 Nosocomial Pathogens and Antibiotic Resistance

Working Group Enterobacteriaceae und Nonfermenter

Research Group A baumannii

Research Group Salmonella

EURL-AR Training Course 2014 Copenhagen

3

Third-party funded research

RESET (ESBL- and Fluoroquinolone Resistance in Enterobacteriacaeae) 2011-2016

Molecular comparison of resistant Enterobacteriaceae from humananimalenvironment

Susceptibility testing and identification of resistance genes

Analysis of new (emerging) resistance genes resistance mechanisms

Characterisation of mobile genetic elements (plasmids integrons IS)

Molecular typing of bacteria (PFGE-analyses MLST etc)

Molecular epidemiology of multidrug-resistant pathogens Emergence and spread of resistance to cephalosporins carbapenems and

fluoroquinolones in gram-negative bacteria in Germany

Topic

Tasks

Yvonne Pfeifer

Working Group bdquoEnterobacteriaceae und Nonfermenterldquo


4 Yvonne Pfeifer

Phenotypic detection of β-lactamases


Which

Why

ESBL AmpC

Carbapenemases

Enterobacteriaceae A baumannii P aeruginosa

Definition of bdquomultidrug-resistanceldquo

Legislation mandatory reporting

In-house surveillance Outbreak investigations Epidemiology nationalinternational Clinical relevance and therapeutic options

Where

5 Yvonne Pfeifer

ESBL Extended-Spectrum β-Lactamases


Usage penicillins cephalosporins 1st2nd generation

ampicillin mezlocillin cefotiam

Extended-Spectrum Beta-Lactamases

TEM-ESBL

SHV-ESBL CTX-M-ESBL

n gt 100 variants

n gt 60 variants

n gt 130 variants

1960

1980

bdquoclassicldquo ESBL in Enterobacteriaceae

cefotaxime ceftazidime cefpodoxime

Usage ldquonewrdquo cephalosporins 3rd generation

1965 Detection of β-lactamases (penicillinases)

1983 Detection of cephalosporinases

TEM-1 und SHV-1 in E coli and K pneumoniae

PER-ESBL

GES-ESBL VEB-ESBL

rare in Enterobacteriaceae A baumannii P aeruginosa

OXA-ESBL

6

β-lactamases class C = AmpC

Yvonne Pfeifer

Plasmid-encoded AmpC β-lactamases

E cloacae

Chromosomal-encoded AmpC β-lactamases

Aeromonas hydrophila

CMY ACC ACT

FOX LAT MOX

Acquired by E coli K pneumoniae Proteus mirabilis

Horizontal gene transfer of formerly chromosomal ampC

Hafnia alvei

E coli

Modifications in regulatory mechanisms result in ampC overexpression rarr Resistance to penicillins and cephalosporins

ampC overexpression due to a promotor of an insertion sequence upstream of the gene rarr Resistance to penicillins und cephalosporins

Citrobacter freundii

Morganella morganii


7

Diagnostics ESBL and AmpC β-lactamases

Resistance to penicillins (ampicillin)

1st 3rd 4th generation cephalosporins (cefotaxime cefpodoxime ceftazidime cefepime)

Resistance to monobactams (aztreonam)

Susceptible to cephamycins (cefoxitin) and carbapenems (imipenem meropenem ertapenem)

ESBL inhibitors clavulanic acid sulbactam tazobactam

Phenotype

Phenotype Resistance to penicillins 1st 3rd gen cephalosporins and cephamycins (cefoxitin cefotetan)

Susceptible to carbapenems

Stable to ESBL inhibitors (clavulanic acid)

AmpC inhibitor cloxacillin

AmpC

Yvonne Pfeifer

Screening Chromogenic agar for selection of bdquoESBL-producingldquo bacteria with cefotaxime (1mgL) or cefpodoxime (4mgL) +- cloxacillin Brilliance ESBL Agar (Oxoid) ChromID ESBL (Biomerieux) Chromagar ESBL (MAST)


8 Yvonne Pfeifer

AST by automated systems

bdquoESBL-positiveldquo cefotaxime- andor ceftazidime-resistant and inhibition by an ESBL inhibitor (clavulanic acid)

bdquoAmpC-positiveldquo bdquohigh-level-cephalosporinaseldquo oder bdquocephamycinaseldquo cefotaxime- andor ceftazidime- andor cefoxitin-resistant und keine No inhibition by an ESBL inhibitor (clavulanic acid)

ESBLAmpC confirmation tests

Etest ESBL cefotaximeceftazidimecefepime + clavulanic acid

Etest AmpC cefotetancefoxitin + cloxacillin

Disk-tests ESBLAMPC Combined-Disk-Tests (CDT)



9

Examples D68C ESBLAmpC ID (Mast) ESBL + AmpC Screen Kit 98008 (Rosco) A cefpodoxime C cefpodoxime + AmpC inhibitor

D cefpodoxime + ESBL- and AmpC inhibitor B cefpodoxime + ESBL inhibitor

ESBL-negative

AmpC-negative

ESBL-positive AmpC-positive ESBL-positive

AmpC-positive

Low -lactamase production false-negative results Production of other -lactamases than ESBLAmpC false positiveno results (eg K1(OXY) β-lactamase in Klebsiella oxytoca)

Limitations

Yvonne Pfeifer

CDT ESBL+AmpC confirmation


10

Limitations CDT ESBL + AmpC confirmation

Yvonne Pfeifer EURL-AR Training Course 2014 Copenhagen

Hyperproducers of K1 β-lactamase can imitate the ESBL-phenotype But consistently resistant to cefuroxime piperacillinndashtazobactam and aztreonam intermediateresistant to cefotaxime and cefepime always fully susceptible to ceftazidime

Phenotype

K1 (OXY) K oxytoca

Potz et al JAC 2004

ESBL or AmpC orhellip

K pneumoniae CTX-M-15 + OXA-48 K pneumoniae KPC-2

resistant subpopulation ldquomultidrug-resistantrdquo

11

K pneumoniae ESBL-type CTX-M-15 E coli ESBL-type CTX-M-1


Etest ESBL + AmpC confirmation

CT cefotaxime

TZ ceftazidime

CTL cefotaxime + clavulanic acid

TZL ceftazidime + clavulanic acid

12 Yvonne Pfeifer EURL-AR Training Course 2014 Copenhagen

Rapid ESBL confirmation

Nordmann P Dortet L Poirel L Rapid detection of extended-spectrum-β-lactamase-producing Enterobacteriaceae J Clin Microbiol 2012 503016-22

This biochemical test (lt1h)was based on the in vitro detection of a cephalosporin (cefotaxime) hydrolysis that is inhibited by tazobactam addition The ESBL activity was evidenced by a color change (red to yellow) of a pH indicator (red phenol) due to carboxyl-acid formation resulting from cefotaxime hydrolysis that was reversed by addition of tazobactam (positive test)

Non-ESBL- producer

ESBL-producer

13 Yvonne Pfeifer

Mechanisms of carbapenem resistance

Efflux-pumps

Loss of porins

Carbapenemase production

Porins = outer menbrane proteins (OMPs) Mutations in different porin genes lead to loss of porins loss of permeability of the cell wall Porin loss + ESBLAmpC production carbapenem resistance (ETP MPM) Common in Enterobacter aerogenes K pneumoniae

Hydrolysis of carbapenems by specific beta-lactamases = carbapenemases

Aktive transport of antibiotics outwards common in Pseudomonas aeruginosa

FIG sitemakerumichedufilesresistancegif

Periplasmic space

Outer membrane

Inner membrane

Beta-lactamase

Periplasmic space Outer membrane


14

KPC bdquoKlebsiella pneumoniae Carbapenemaseldquo mainly in K pneumoniae

Common in bdquoendemic areasldquo (eg Greece Israel Italy)

VIM bdquoVerona Integron-borne Metallo-beta-lactamaseldquo in Enterobacteriaceae and P aeruginosa common in Mediterranean countries (Italy Greece)

NDM bdquoNew-Delhi Metallo-Beta-Lactamaseldquo in Enterobacteriaceae and A baumannii from India North Africa Balkan states

OXA-48 in Enterobacteriaceae common in Turkey North Africa India

OXA-582324 common in A baumannii

metallo-beta-lactamases (MBL)

Carbapenemases

Yvonne Pfeifer

IMP rare in E cloacae K pneumoniae more common in P aeruginosa

GIM bdquoGerman Imipenemaseldquo single cases in E cloacae S marcescens P aeruginosa A pittii

AIM bdquoAdelaide Imipenemaseldquo single cases in P aeruginosa

FIM bdquoFlorence Imipenemaseldquo single cases in P aeruginosa

DIM bdquoDutch Imipenemaseldquo single cases in Pseudomonas spp

SIM bdquoSeoul Imipenemaseldquo single cases in A baumannii

SPM bdquoSatildeo Paulo metallo-β-lactamaseldquo single cases in P aeruginosa



Canton R et al CMI 2012

Spread of carbapenemases in Europe

16

Carbapenemases

Carbapenemases in Germany

Cases of carbapenemase-producing gram-negative bacteria 2009-2013

Data from the National Reference Center of gram-negative nosocomial pathogens in Bochum (Dr Martin Kaase)

Yvonne Pfeifer

Enterobacteriaceae tested in 2013 n = 1831

Carbapenemase producers in 2013 n = 699 (K pneumoniae n = 481 E coli n = 73)


17

Antibiotics [mgmL] NDM-1 E coli

VIM-1 K oxytoca

KPC-2 K pneumoniae

OXA-48 + ESBL K pneumoniae

OXA-48 E coli

Ampicillin R R R R R

PIPTAZ R R R R R

Cefotaxime R R R R S

Ceftazidime R R R R S

Cefoxitin R R R R R

Gentamicin R R I R R

Amikacin R S R R R

Oxytetracycline R R R R R

Chloramphenicol R R R R R

Ciprofloxacin R R R R R

SXT R R R R R

Meropenem R R R R I

Imipenem R R R R I

Ertapenem R R R R R

MBL-Etest (IPIPI) positiv positiv negativ negativ negativ

Tigecycline I S I S S

Colistin S S S S S

Yvonne Pfeifer

Phenotype Carbapenemase producers


18

Diagnostics Carbapenemases

Phenotype Resistance to penicillins 1st-4th gen cephalosporins and carbapenems

Metallo-beta-lactamases (MBL) susceptible to aztreonam


Carbapenemase inhibitors EDTA (MBL) boric acid (KPC)


Screening

Brilliance CRE Agar (Oxoid) ChromID Carba (Biomerieux) Chromagar KPC (MAST) SUPERCARBA medium (Nordmann Pet al JCM 2012)

Chromogenic agar for selection of bdquoCarbapenemase-producingldquo bacteria with Meropenem oder Ertapenem (Girlich et al 2013 Diagn Microbiol Infect Dis)

Carbapenemase producer

OXA-48 carbapenemases susceptible to 3rd gen cephalosporins

19



bdquoCarbapenemase producer (KPC or MBL) or loss of permeability + ESBLhigh-level-cephalosporinaseldquo resistantintermediate-resistant to imipenemmeropemen ertapenem

Yvonne Pfeifer

Manual confirmation tests is needed


Carbapenemase confirmation tests

Etest MBL imipenem + imipenemEDTA

Disk-Tests CDT with carbapenemase inhibitors


mod Hodge Test imipenemmeropenem-hydrolysis (Carba NP MALDI)

20

Diagnostics carbapenemase production

Yvonne Pfeifer

Mod Hodge-Test

E coli ndash reference strain carbapenem-susceptible

K pneumoniae carbapenem-susceptible K pneumoniae

carbapenemase producer

Modified Hodge Test

- Confirmation of any carbapenamase production (OXA-48 KPC MBL)

- reliable for outbreak investigations

- low specifity - false positive results (eg AmpC producer) are common

Disks

Imipenem

Meropenem

Ertapenem

Girlich D Poirel L Nordmann P 2012 Value of the modified Hodge test for detection of emerging carbapenemases in Enterobacteriacae J Clin Microbiol 50 477-479

K pneumoniae carbapenem-resistant but no carbapenemase production


21

Rapid detection Carbapenemase production


Carba NP Test Nordmann P Poirel L Dortet L Rapid detection of carbapenemase-producing Enterobacteriaceae Emerg Infect Dis 2012 181503-7

To rapidly identify carbapenemase producers in Enterobacteriaceae we developed the Carba NP test The test uses isolated bacterial colonies and is based on in vitro hydrolysis of a carbapenem imipenem It was 100 sensitive and specific compared with molecular-based techniques This rapid (lt2 hours) inexpensive technique may be implemented in any laboratory

22



Blue Carba Test

Imipenemmeropenem hydrolysis + confirmation with UV-Spec or MALDI-TOF

Bernabeu et al DMID 2012

Hrabaacutek et al JCM 2012

Burckhardt et al JCM 2011

J Clin Microbiol Dec 2013 51(12) 4281ndash4283

Blue-Carba an Easy Biochemical Test for Detection of Diverse Carbapenemase Producers Directly from Bacterial Cultures

J Pires Acirc Novais and L Peixe

Advantages direct use of colonies (instead of bacterial extracts that need the extraction buffer (B-PER II) reduced cost per reaction due to use of Tienam (ca 10times cheaper than an imipenem monohydrate formula)

23 Yvonne Pfeifer

bdquoKPCMBLAmpC ID-Testldquo (Rosco Diagn) or bdquoCarba-D70Cldquo Test (MAST Diagn)

MRP Meropenem

MR+DP Meropenem + MBL inhibitor MR+CL Meropenem + AmpC inhibitor

MR+BO Meropenem + KPC inhibitor

Boric acid derivate = KPC inhibitor EDTA derivate = MBL inhibitor

KPC-positive MBL-positive (eg VIM NDM)

CDT Carbapenemase confirmation


24

Limitations CDT Carbapenemase confirmation


Carbapenemase or no carbapenemase

P aeruginosa carbapenem resistant

K pneumoniae CTX-M-15 + OXA-48

K pneumoniae carbapenem resistant

MRP Meropenem



P aeruginosa without carbapenemase

Mod Hodge-Test positive

25

Etest Metallo-beta-lactamases (MBL)


Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1

Metallo-β-lactamase-positive

Deformation of ellipsephantom zone

26

Limitations Etest metallo-beta-lactamases (MBL)


Metallo-β-lactamase-negative

K neumoniae OXA-48

K pneumoniae MIC imipenem 4mgL


Metallo-β-lactamase-suspicious

S marcescens GIM-1 (MBL)

MIC meropenem 2mgL MIC ertapenem gt32mgL

S marcescens MIC imipenem 1mgL

Mod Hodge-Test +-

MIC meropenem 1mgL MIC ertapenem 4mgL

Phantom zone

27

Limitations Etest MBL and P aeruginosa


P aeruginosa P aeruginosa P aeruginosa

Resistant

subpopulation

Phantom zone

A) B) C)

MBL-suspicious MBL-suspicious MBL-positive

28

Limitations Etest MBL and Nonfermenter



IP Imipenem

IPI Imipenem+EDTA

narrow ellipse

General growth inhibition due to EDTA independently from MBL-production

The imipenemEDTA inhibition zone is a bdquonarrow ellipseldquo

common in carbapenem-resistant P aeruginosa or A baumannii producing OXA carbapenemases

false-positive MBL-test

Yvonne Pfeifer 29

Carbapenemases and A baumannii

gt 95 of all carbapenem-resistant A baumannii produce a carbapenemase

VIM

NDM-1

Carbapenem resistance

OXA-23 OXA-72 OXA-58 OXA-51+ISAba1

Metallo-beta-lactamases (MBL) rare but increasing in A baumannii

Common and wide spread in MDR-A baumannii

IMP

intermediateresistant to imipenem and meropenem

Mod Hodge Test Mainly positive (or false positive due to AmpC-production)

MBL-Etest Often false positive (growth inhibition by EDTA)

Disk-Test No results or false positive results (growth inhibition by EDTA)

Is phenotypic confirmation really necessary for carbapenem-resistant A baumannii


Yvonne Pfeifer 30

Carbapenem resistance and porin loss


Cause

Porins = OMPs = outer menbrane proteins

Mutations in porin genes porin loss (loss of permeability)

AMP PIPTAZ CTX CAZ FOX IPM MPM ETP

R R R R R 025 - gt 32 05 - gt 32 R

Porin loss + ESBLAmpC- production carbapenem resistance

Phenotype

Common resistance mechanism in Enterobacter aerogenes (gt95)

Common in K pneumoniae (after therapy with carbapenems)

Ertapenem-resistant

PIPTAZ-resistant

MIC imipenem lt= MIC meropenem AMP ampicillin PIPTAZ piperacillintazobactam CTX cefotaxime CAZ ceftazidime ETP ertapenem MPM meropenem IPM imipenem FOX cefoxitin

31

KPC = Klebsiella pneumoniae carbapenemase

Yvonne Pfeifer

AMP PIPTAZ CTX IPM MPM ETP

R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC

Mainly in K pneumoniae due to worldwide spread of clonal lineages (K pneumoniae ST258ST512 with KPC-2 orKPC-3)

Transfer of KPC-plasmidstransposons in other Enterobacteriaceae

Ertapenem-resistant

Mainly resistant to imipenem and meropenem (isolates of clonal lineages)

MIC imipenem gt= MIC meropenem

PIPTAZ-resistant Phenotypical confirmation

mod Hodge Test (Carba-NP-Test MALDI-TOF)

Disk-Tests with carbapenem + boric acid (KPC inhibitor)


AMP ampicillin PIPTAZ piperacillintazobactam CTX cefotaxime CAZ ceftazidime ETP ertapenem MPM meropenem IPM imipenem

32 Yvonne Pfeifer

OXA-48 Carbapenemase

AMP PIPTAZ CTX CAZ IPM MPM ETP

R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R

Phenotype OXA-48 + ESBL


Common carbapenemase in K pneumoniae E coli and other Enterobacteriaceae

Ertapenem-resistant


PIPTAZ-resistant

Susceptible to ceftazidimecefotaxime (if there is no ESBL present)

Resistance to temocillin

Phenotypical confirmation mod Hodge Test (Carba-NP-Test MALDI-TOF)


33

chromIDreg CARBA SMART

Example Screening KPC + OXA-48

KPCMBL selective

OXA-48 selective

Study Screening (rectal swabs) of patients with KPC-producer colonisation

Red = KPC-2 E coli

Blue = KPC-2 K pneumoniae

Grey = KPC-2 C freundii (outbreak strain)

KPC OXA-48


34 Yvonne Pfeifer

Metallo-beta-lactamases

AMP PIPTAZ CTX ATM IPM MPM ETP

R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM

Common in Enterobacteriaceae (esp E cloacae K pneumoniae K oxytoca) and P aeruginosa (VIM-type)

Ertapenem-resistant


PIPTAZ-resistant

Susceptible to aztreonam (if there is no ESBL present) Phenotypical confirmation

mod Hodge Test (Carba NP test Maldi-TOF etc)

MBL-Etest

MBL-Disk tests with carbapenems + EDTA (MBL inhibitor)



35

Summary

Yvonne Pfeifer

bull ESBL confirmation Automated systems Etest disk-test are reliable tools

bull AmpC confirmation Etest disk-test (automated systems) are reliable tools

bull No ESBLAmpC confirmation is needed for A baumanniiP aeruginosa

bull Continuous problems K oxytoca (ESBL or K1 hyperproducer)

bull Carbapenemase confirmation Etest disk-test (automated systems) are reliable tools

bull Continuous problems mod Hodge Test (low specifity)


low β-lactamase production (sensitivity)

production of many β-lactamases

low carbapenemase production (sensitivity)

no inhibitors for OXA carbapenemases

false-positive MBL-results A baumanniiP aeruginosa

Inconsistent results Confirmation of phenotype by molecular methods

Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner

National Reference Center Staphylococci (MRSA) Enterococci


Working group bdquoEnterobacteriaceae and Nonfermenterldquo

Sibylle Muumlller-Bertling

Robert Koch Institute Berlin

Prof Dr Martin Mielke Dr Tim Eckmanns

pfeiferyrkide


Yvonne Pfeifer 2


National Reference Center Staphylococci (MRSA) and Enterococci

Department 11 Bacterial Enteric Pathogens and Legionella

National Reference Center Salmonella and other Enteric Pathogens

Department 13 Nosocomial Pathogens and Antibiotic Resistance

Working Group Enterobacteriaceae und Nonfermenter

Research Group A baumannii

Research Group Salmonella


3










Topic

Tasks

Yvonne Pfeifer



4 Yvonne Pfeifer



Which

Why

ESBL AmpC

Carbapenemases





Where

5 Yvonne Pfeifer






TEM-ESBL

SHV-ESBL CTX-M-ESBL

n gt 100 variants

n gt 60 variants

n gt 130 variants

1960

1980







PER-ESBL

GES-ESBL VEB-ESBL


OXA-ESBL

6


Yvonne Pfeifer


E cloacae



CMY ACC ACT

FOX LAT MOX



Hafnia alvei

E coli




Morganella morganii


7







Phenotype





AmpC

Yvonne Pfeifer



8 Yvonne Pfeifer










9



ESBL-negative

AmpC-negative


AmpC-positive


Limitations

Yvonne Pfeifer



10




Phenotype

K1 (OXY) K oxytoca

Potz et al JAC 2004




11




CT cefotaxime

TZ ceftazidime







Non-ESBL- producer

ESBL-producer

13 Yvonne Pfeifer


Efflux-pumps

Loss of porins






Periplasmic space

Outer membrane

Inner membrane

Beta-lactamase



14








Carbapenemases

Yvonne Pfeifer












16

Carbapenemases




Yvonne Pfeifer




17


VIM-1 K oxytoca

KPC-2 K pneumoniae


OXA-48 E coli


PIPTAZ R R R R R



Cefoxitin R R R R R


Amikacin R S R R R




SXT R R R R R

Meropenem R R R R I

Imipenem R R R R I

Ertapenem R R R R R



Colistin S S S S S

Yvonne Pfeifer



18







Screening





19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


3










Topic

Tasks

Yvonne Pfeifer



4 Yvonne Pfeifer



Which

Why

ESBL AmpC

Carbapenemases





Where

5 Yvonne Pfeifer






TEM-ESBL

SHV-ESBL CTX-M-ESBL

n gt 100 variants

n gt 60 variants

n gt 130 variants

1960

1980







PER-ESBL

GES-ESBL VEB-ESBL


OXA-ESBL

6


Yvonne Pfeifer


E cloacae



CMY ACC ACT

FOX LAT MOX



Hafnia alvei

E coli




Morganella morganii


7







Phenotype





AmpC

Yvonne Pfeifer



8 Yvonne Pfeifer










9



ESBL-negative

AmpC-negative


AmpC-positive


Limitations

Yvonne Pfeifer



10




Phenotype

K1 (OXY) K oxytoca

Potz et al JAC 2004




11




CT cefotaxime

TZ ceftazidime







Non-ESBL- producer

ESBL-producer

13 Yvonne Pfeifer


Efflux-pumps

Loss of porins






Periplasmic space

Outer membrane

Inner membrane

Beta-lactamase



14








Carbapenemases

Yvonne Pfeifer












16

Carbapenemases




Yvonne Pfeifer




17


VIM-1 K oxytoca

KPC-2 K pneumoniae


OXA-48 E coli


PIPTAZ R R R R R



Cefoxitin R R R R R


Amikacin R S R R R




SXT R R R R R

Meropenem R R R R I

Imipenem R R R R I

Ertapenem R R R R R



Colistin S S S S S

Yvonne Pfeifer



18







Screening





19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


4 Yvonne Pfeifer



Which

Why

ESBL AmpC

Carbapenemases





Where

5 Yvonne Pfeifer






TEM-ESBL

SHV-ESBL CTX-M-ESBL

n gt 100 variants

n gt 60 variants

n gt 130 variants

1960

1980







PER-ESBL

GES-ESBL VEB-ESBL


OXA-ESBL

6


Yvonne Pfeifer


E cloacae



CMY ACC ACT

FOX LAT MOX



Hafnia alvei

E coli




Morganella morganii


7







Phenotype





AmpC

Yvonne Pfeifer



8 Yvonne Pfeifer










9



ESBL-negative

AmpC-negative


AmpC-positive


Limitations

Yvonne Pfeifer



10




Phenotype

K1 (OXY) K oxytoca

Potz et al JAC 2004




11




CT cefotaxime

TZ ceftazidime







Non-ESBL- producer

ESBL-producer

13 Yvonne Pfeifer


Efflux-pumps

Loss of porins






Periplasmic space

Outer membrane

Inner membrane

Beta-lactamase



14








Carbapenemases

Yvonne Pfeifer












16

Carbapenemases




Yvonne Pfeifer




17


VIM-1 K oxytoca

KPC-2 K pneumoniae


OXA-48 E coli


PIPTAZ R R R R R



Cefoxitin R R R R R


Amikacin R S R R R




SXT R R R R R

Meropenem R R R R I

Imipenem R R R R I

Ertapenem R R R R R



Colistin S S S S S

Yvonne Pfeifer



18







Screening





19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


5 Yvonne Pfeifer






TEM-ESBL

SHV-ESBL CTX-M-ESBL

n gt 100 variants

n gt 60 variants

n gt 130 variants

1960

1980







PER-ESBL

GES-ESBL VEB-ESBL


OXA-ESBL

6


Yvonne Pfeifer


E cloacae



CMY ACC ACT

FOX LAT MOX



Hafnia alvei

E coli




Morganella morganii


7







Phenotype





AmpC

Yvonne Pfeifer



8 Yvonne Pfeifer










9



ESBL-negative

AmpC-negative


AmpC-positive


Limitations

Yvonne Pfeifer



10




Phenotype

K1 (OXY) K oxytoca

Potz et al JAC 2004




11




CT cefotaxime

TZ ceftazidime







Non-ESBL- producer

ESBL-producer

13 Yvonne Pfeifer


Efflux-pumps

Loss of porins






Periplasmic space

Outer membrane

Inner membrane

Beta-lactamase



14








Carbapenemases

Yvonne Pfeifer












16

Carbapenemases




Yvonne Pfeifer




17


VIM-1 K oxytoca

KPC-2 K pneumoniae


OXA-48 E coli


PIPTAZ R R R R R



Cefoxitin R R R R R


Amikacin R S R R R




SXT R R R R R

Meropenem R R R R I

Imipenem R R R R I

Ertapenem R R R R R



Colistin S S S S S

Yvonne Pfeifer



18







Screening





19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


6


Yvonne Pfeifer


E cloacae



CMY ACC ACT

FOX LAT MOX



Hafnia alvei

E coli




Morganella morganii


7







Phenotype





AmpC

Yvonne Pfeifer



8 Yvonne Pfeifer










9



ESBL-negative

AmpC-negative


AmpC-positive


Limitations

Yvonne Pfeifer



10




Phenotype

K1 (OXY) K oxytoca

Potz et al JAC 2004




11




CT cefotaxime

TZ ceftazidime







Non-ESBL- producer

ESBL-producer

13 Yvonne Pfeifer


Efflux-pumps

Loss of porins






Periplasmic space

Outer membrane

Inner membrane

Beta-lactamase



14








Carbapenemases

Yvonne Pfeifer












16

Carbapenemases




Yvonne Pfeifer




17


VIM-1 K oxytoca

KPC-2 K pneumoniae


OXA-48 E coli


PIPTAZ R R R R R



Cefoxitin R R R R R


Amikacin R S R R R




SXT R R R R R

Meropenem R R R R I

Imipenem R R R R I

Ertapenem R R R R R



Colistin S S S S S

Yvonne Pfeifer



18







Screening





19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


7







Phenotype





AmpC

Yvonne Pfeifer



8 Yvonne Pfeifer










9



ESBL-negative

AmpC-negative


AmpC-positive


Limitations

Yvonne Pfeifer



10




Phenotype

K1 (OXY) K oxytoca

Potz et al JAC 2004




11




CT cefotaxime

TZ ceftazidime







Non-ESBL- producer

ESBL-producer

13 Yvonne Pfeifer


Efflux-pumps

Loss of porins






Periplasmic space

Outer membrane

Inner membrane

Beta-lactamase



14








Carbapenemases

Yvonne Pfeifer












16

Carbapenemases




Yvonne Pfeifer




17


VIM-1 K oxytoca

KPC-2 K pneumoniae


OXA-48 E coli


PIPTAZ R R R R R



Cefoxitin R R R R R


Amikacin R S R R R




SXT R R R R R

Meropenem R R R R I

Imipenem R R R R I

Ertapenem R R R R R



Colistin S S S S S

Yvonne Pfeifer



18







Screening





19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


8 Yvonne Pfeifer










9



ESBL-negative

AmpC-negative


AmpC-positive


Limitations

Yvonne Pfeifer



10




Phenotype

K1 (OXY) K oxytoca

Potz et al JAC 2004




11




CT cefotaxime

TZ ceftazidime







Non-ESBL- producer

ESBL-producer

13 Yvonne Pfeifer


Efflux-pumps

Loss of porins






Periplasmic space

Outer membrane

Inner membrane

Beta-lactamase



14








Carbapenemases

Yvonne Pfeifer












16

Carbapenemases




Yvonne Pfeifer




17


VIM-1 K oxytoca

KPC-2 K pneumoniae


OXA-48 E coli


PIPTAZ R R R R R



Cefoxitin R R R R R


Amikacin R S R R R




SXT R R R R R

Meropenem R R R R I

Imipenem R R R R I

Ertapenem R R R R R



Colistin S S S S S

Yvonne Pfeifer



18







Screening





19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


9



ESBL-negative

AmpC-negative


AmpC-positive


Limitations

Yvonne Pfeifer



10




Phenotype

K1 (OXY) K oxytoca

Potz et al JAC 2004




11




CT cefotaxime

TZ ceftazidime







Non-ESBL- producer

ESBL-producer

13 Yvonne Pfeifer


Efflux-pumps

Loss of porins






Periplasmic space

Outer membrane

Inner membrane

Beta-lactamase



14








Carbapenemases

Yvonne Pfeifer












16

Carbapenemases




Yvonne Pfeifer




17


VIM-1 K oxytoca

KPC-2 K pneumoniae


OXA-48 E coli


PIPTAZ R R R R R



Cefoxitin R R R R R


Amikacin R S R R R




SXT R R R R R

Meropenem R R R R I

Imipenem R R R R I

Ertapenem R R R R R



Colistin S S S S S

Yvonne Pfeifer



18







Screening





19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


10




Phenotype

K1 (OXY) K oxytoca

Potz et al JAC 2004




11




CT cefotaxime

TZ ceftazidime







Non-ESBL- producer

ESBL-producer

13 Yvonne Pfeifer


Efflux-pumps

Loss of porins






Periplasmic space

Outer membrane

Inner membrane

Beta-lactamase



14








Carbapenemases

Yvonne Pfeifer












16

Carbapenemases




Yvonne Pfeifer




17


VIM-1 K oxytoca

KPC-2 K pneumoniae


OXA-48 E coli


PIPTAZ R R R R R



Cefoxitin R R R R R


Amikacin R S R R R




SXT R R R R R

Meropenem R R R R I

Imipenem R R R R I

Ertapenem R R R R R



Colistin S S S S S

Yvonne Pfeifer



18







Screening





19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


11




CT cefotaxime

TZ ceftazidime







Non-ESBL- producer

ESBL-producer

13 Yvonne Pfeifer


Efflux-pumps

Loss of porins






Periplasmic space

Outer membrane

Inner membrane

Beta-lactamase



14








Carbapenemases

Yvonne Pfeifer












16

Carbapenemases




Yvonne Pfeifer




17


VIM-1 K oxytoca

KPC-2 K pneumoniae


OXA-48 E coli


PIPTAZ R R R R R



Cefoxitin R R R R R


Amikacin R S R R R




SXT R R R R R

Meropenem R R R R I

Imipenem R R R R I

Ertapenem R R R R R



Colistin S S S S S

Yvonne Pfeifer



18







Screening





19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide






Non-ESBL- producer

ESBL-producer

13 Yvonne Pfeifer


Efflux-pumps

Loss of porins






Periplasmic space

Outer membrane

Inner membrane

Beta-lactamase



14








Carbapenemases

Yvonne Pfeifer












16

Carbapenemases




Yvonne Pfeifer




17


VIM-1 K oxytoca

KPC-2 K pneumoniae


OXA-48 E coli


PIPTAZ R R R R R



Cefoxitin R R R R R


Amikacin R S R R R




SXT R R R R R

Meropenem R R R R I

Imipenem R R R R I

Ertapenem R R R R R



Colistin S S S S S

Yvonne Pfeifer



18







Screening





19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


13 Yvonne Pfeifer


Efflux-pumps

Loss of porins






Periplasmic space

Outer membrane

Inner membrane

Beta-lactamase



14








Carbapenemases

Yvonne Pfeifer












16

Carbapenemases




Yvonne Pfeifer




17


VIM-1 K oxytoca

KPC-2 K pneumoniae


OXA-48 E coli


PIPTAZ R R R R R



Cefoxitin R R R R R


Amikacin R S R R R




SXT R R R R R

Meropenem R R R R I

Imipenem R R R R I

Ertapenem R R R R R



Colistin S S S S S

Yvonne Pfeifer



18







Screening





19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


14








Carbapenemases

Yvonne Pfeifer












16

Carbapenemases




Yvonne Pfeifer




17


VIM-1 K oxytoca

KPC-2 K pneumoniae


OXA-48 E coli


PIPTAZ R R R R R



Cefoxitin R R R R R


Amikacin R S R R R




SXT R R R R R

Meropenem R R R R I

Imipenem R R R R I

Ertapenem R R R R R



Colistin S S S S S

Yvonne Pfeifer



18







Screening





19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide





16

Carbapenemases




Yvonne Pfeifer




17


VIM-1 K oxytoca

KPC-2 K pneumoniae


OXA-48 E coli


PIPTAZ R R R R R



Cefoxitin R R R R R


Amikacin R S R R R




SXT R R R R R

Meropenem R R R R I

Imipenem R R R R I

Ertapenem R R R R R



Colistin S S S S S

Yvonne Pfeifer



18







Screening





19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


17


VIM-1 K oxytoca

KPC-2 K pneumoniae


OXA-48 E coli


PIPTAZ R R R R R



Cefoxitin R R R R R


Amikacin R S R R R




SXT R R R R R

Meropenem R R R R I

Imipenem R R R R I

Ertapenem R R R R R



Colistin S S S S S

Yvonne Pfeifer



18







Screening





19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


18







Screening





19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


19




Yvonne Pfeifer








20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


20


Yvonne Pfeifer

Mod Hodge-Test




Modified Hodge Test




Disks

Imipenem

Meropenem

Ertapenem




21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


21





22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


22



Blue Carba Test









23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


23 Yvonne Pfeifer


MRP Meropenem







24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


24







MRP Meropenem





25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


25



Imipenem

K pneumoniae VIM-1

Imipenem + EDTA

(MBL inhibitor)

E coli NDM-1



26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


26




K neumoniae OXA-48







Mod Hodge-Test +-


Phantom zone

27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


27




Resistant

subpopulation

Phantom zone

A) B) C)


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


28




IP Imipenem

IPI Imipenem+EDTA

narrow ellipse





Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


Yvonne Pfeifer 29



VIM

NDM-1





IMP







Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


Yvonne Pfeifer 30



Cause




R R R R R 025 - gt 32 05 - gt 32 R


Phenotype



Ertapenem-resistant

PIPTAZ-resistant


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


31


Yvonne Pfeifer


R R R 05 - gt 32 025 - gt 32 R

Phenotype

KPC



Ertapenem-resistant








32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


32 Yvonne Pfeifer



R R SI S 05 - gt 32 025 - gt 32 R

Phenotype

OXA-48


R R R IR 05 - gt 32 025 - gt 32 R




Ertapenem-resistant


PIPTAZ-resistant





33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


33



KPCMBL selective

OXA-48 selective


Red = KPC-2 E coli



KPC OXA-48


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


34 Yvonne Pfeifer



R R R S 05 - gt 32 025 - gt 32 R

Phenotype

VIMNDM


Ertapenem-resistant


PIPTAZ-resistant



MBL-Etest




35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


35

Summary

Yvonne Pfeifer














Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


Yvonne Pfeifer 36

Thank you

PD Dr Guido Werner







pfeiferyrkide


interpretation of esbl and carbapenemase phenotypes · 6 β-lactamases class c = ampc yvonne...

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