1. 2 Extended-Spectrum-β Lactamase (ESBLs) Extended-Spectrum-β Lactamase (ESBLs) 3.
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Transcript of 1. 2 Extended-Spectrum-β Lactamase (ESBLs) Extended-Spectrum-β Lactamase (ESBLs) 3.
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Extended-Extended-Spectrum-Spectrum-ββ LactamaseLactamase
(ESBLs)(ESBLs)
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HistoryHistory
Pul Ehrlis 1910 Salvarsan Pul Ehrlis 1910 Salvarsan Gerhard Domagk 1935 Sulfanilamid Gerhard Domagk 1935 Sulfanilamid Alexander Fleming 1929 Penicillin Alexander Fleming 1929 Penicillin Ernest Chain and Howard Florey 1941 Ernest Chain and Howard Florey 1941 the drug was testedthe drug was tested
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Classes of antibacterial agentsClasses of antibacterial agents
Basis of the mechanism of action: Basis of the mechanism of action: 1-Inhibitors of cell wall synthesis 1-Inhibitors of cell wall synthesis 2-Inhibitors of cytoplasmic membrane 2-Inhibitors of cytoplasmic membrane function function 3-Inhibitors of protein synthesis 3-Inhibitors of protein synthesis 4-Inhibitors of nucleic acid 4-Inhibitors of nucleic acid synthesis 5-antimetabolitessynthesis 5-antimetabolites
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Inhibitors of cell wall synthesisInhibitors of cell wall synthesis
11--Beta- lactams Beta- lactams Penicillins,Cephalosporins,Carbapenems, Penicillins,Cephalosporins,Carbapenems, Monobactams Monobactams 2-Glycopeptides: 2-Glycopeptides: Vancomycin,teicoplani (active only Vancomycin,teicoplani (active only against G-P)against G-P)
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-Lactams: Classification (1)-Lactams: Classification (1)PenicillinsPenicillins
Narrow-spectrum penicillinsNarrow-spectrum penicillinsBroad-spectrum penicillinsBroad-spectrum penicillins
ββ-lactamase inhibitor combinations-lactamase inhibitor combinationsOxacillin derivativesOxacillin derivatives
Cephalosporins (ATC/WHO 2005 classification)Cephalosporins (ATC/WHO 2005 classification)1st generation: Gram-positive cocci (GPCs), some 1st generation: Gram-positive cocci (GPCs), some
Gram-negative bacilli (GNBs)Gram-negative bacilli (GNBs)2nd generation: some GNBs, anaerobes2nd generation: some GNBs, anaerobes
3rd generation: many GNBs, GPCs3rd generation: many GNBs, GPCs 4th generation: many GNBs resistant to 3rd 4th generation: many GNBs resistant to 3rd
generation, GPCsgeneration, GPCs
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-Lactams: Classification (2)-Lactams: Classification (2)
CarbapenemsCarbapenemsImipenem, meropenem, ertapenemImipenem, meropenem, ertapenem
MonobactamsMonobactamsAztreonamAztreonam
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1111
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The β-lactam family of antibioticsThe β-lactam family of antibiotics
Ceftriaxone 3Ceftriaxone 3rdrdTicarcillinTicarcillin
Ceftazidime Ceftazidime 33rdrd
MezlocillinMezlocillin
Cefotaxime Cefotaxime 33rdrd
CarbenicillinCarbenicillin
ErtapenemErtapenemCefmetazolCefmetazolee
Cefuroxime Cefuroxime 22ndndAmpicillinAmpicillin
MeropenemMeropenemCefotetanCefotetanCefamandole Cefamandole
22ndndMethicillinMethicillin
AztreonamAztreonamImipenemImipenemCefoxitinCefoxitinCephalothin Cephalothin 11stst
Benzyl-Benzyl-penicillinpenicillin
MonobactaMonobactamsms
CarbapenemCarbapenemss
CephamycinCephamycinss
CephalosporinCephalosporinss
PenicillinsPenicillins
Cefepime 4Cefepime 4thth
DefinitionsDefinitions
Narrow-spectrum Narrow-spectrum -lactam agents-lactam agentsActive against G- or G+ bacteria only; e.g., Active against G- or G+ bacteria only; e.g.,
penicillinpenicillin
Broad-spectrum Broad-spectrum -lactam agents-lactam agentsActive against G- and G+ bacteria; e.g., Active against G- and G+ bacteria; e.g.,
ampicillin, 1ampicillin, 1stst generation cephalosporins generation cephalosporins
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Definitions (con’t)Definitions (con’t)
Extended-spectrum ß-lactam agentsExtended-spectrum ß-lactam agentsEnhanced activity against G- and some G+ Enhanced activity against G- and some G+
bacteria; e.g., 3bacteria; e.g., 3rdrd and 4 and 4thth generation generation cephalosporins, carboxy- and cephalosporins, carboxy- and ureidopenicillinsureidopenicillins
Extended-spectrum ß-lactamases Extended-spectrum ß-lactamases (ESBLs)(ESBLs)
Enzymes produced by GNR that destroy Enzymes produced by GNR that destroy certain extended-spectrum ß-lactam agents, certain extended-spectrum ß-lactam agents, including including 33rdrd generation cephalosporins generation cephalosporins
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Mechanism of actionMechanism of action
Binding to penicillin Binding Protein(P B P) Binding to penicillin Binding Protein(P B P) this protein are this protein are carboxypeptidase ,aminopeptidase and carboxypeptidase ,aminopeptidase and transpeptidase enzymes transpeptidase enzymes Inhibition of one or more of this Inhibition of one or more of this enzymes accumulation of precursor cell enzymes accumulation of precursor cell wall unit cell's autolytic system to be wall unit cell's autolytic system to be activated and results finally cell lysesactivated and results finally cell lyses
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Resistance to Resistance to -Lactams-Lactams
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ResistanceResistance
11--Alteration in target site Alteration in target site 2-Production of beta- lactamases2-Production of beta- lactamases Genes encoding are found on the Genes encoding are found on the chromosome (generally G-N) and on the chromosome (generally G-N) and on the plasmid (generally G-P )plasmid (generally G-P )
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Beta-lactamase inhibitorsBeta-lactamase inhibitors
Resemble β-lactam antibiotic structureResemble β-lactam antibiotic structureBind to β-lactamase and protect the Bind to β-lactamase and protect the
antibiotic from destructionantibiotic from destructionMost successful when they bind the β-Most successful when they bind the β-
lactamase irreversiblylactamase irreversiblyThree important in medicineThree important in medicine
Clavulanic acidClavulanic acidSulbactamSulbactam
TazobactamTazobactam
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ββ-lactamase inhibitors-lactamase inhibitors
Clavulonic acid: derived from Clavulonic acid: derived from Streptomyces clavuligerusStreptomyces clavuligerusLittle antibiotic effect in itselfLittle antibiotic effect in itself
Given in combination with a Given in combination with a ββ -lactam Ab -lactam AbFunction: by binding the Function: by binding the ββ -lactamase enzyme more -lactamase enzyme more
efficiently than the actual efficiently than the actual ββ -lactam -lactamThus protect the Thus protect the ββ -lactam Ab from hydrolysis -lactam Ab from hydrolysis
Not efficient against cephalosporinasesNot efficient against cephalosporinases
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Plasmid-mediated TEM and SHV -lactamases
Ampicillin
1965
TEM-1E.coliS.paratyphi
1970s
TEM-1Reported in 28 Gm(-) sp
1983
ESBL in Europe
1988
ESBL in USA
2000
> 130 ESBLsWorldwide
Extended-spectrumCephalosporins
1963
Evolution of -Lactamases
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History of GNR resistanceHistory of GNR resistance
1928
Fleming
1941
Penicillin use
1940 Penicillinase detected in E.
coli
1959
β -lactamase resistant penicillins: Methicillin
1960s
Broad spectrum/ extended spectrum
penicillins
1964
Cefalotin use
1965
Broad spectrum β –lactamases (TEM-1 in E. coli) 1983 Extended
spectrum β-lactamases
1950 1960 1970 1980 1990 2000
1985
Carbapenem (Imipenem)
Early 1980s
3rd generation ceph.
Carbapenemases
TEM-1 widespread
2005
Tigecycline
ESBL outbreaks in
France
1976
β –lactamases inhibitors
2424
Ambler Ambler Classification of Classification of ββ--LactamasesLactamases
Active site
Nucleotide sequence
Four evolutionarily distinct molecular classes
A C D
Serine-enzymes
B
Zinc-enzymes
β-lactamases
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Modified Modified Bush–Jacoby–Medeiros Bush–Jacoby–Medeiros CClassification of lassification of –Lactamases–Lactamases
Functional Substrate profile Group
Molecular Class
Inhibitor
Example
1 Cephalosporinase C Oxa AmpC, MIR-1
2a Penicillinase A Clav. S.aureus
2b Broad spectrum A Clav. TEM-1/2, SHV-1
2be Extended spectrum A Clav. TEM 3-29, TEM46-104 SHV2-28, CTX-M types
2br Inhibition resistant A - TEM 30-41 (IRT1-12)
2c Carbenicillinase A Clav. PSE-1
2d Oxacillinase D (Clav.) OXA-1 (OXA-2 &-10 derived ESBL)
2e Cephalosporinase A Clav. FPM-1 P. vulgaris, CepA B. fragilis.
2f Carbapenemase A Clav. IMI-1, NmcA, Sme 1-3
3 Metallo-enzyme B - S.maltophilia
4 Penicillinase - - B.cepacia
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Extended-Spectrum Extended-Spectrum -Lactamases (ESBL)-Lactamases (ESBL)
Confers resistance to penicillins andConfers resistance to penicillins and 11stst, 2, 2ndnd and 3 and 3rdrd generation cephalosporins generation cephalosporins
Inhibited by Inhibited by -Lactamase inhibitors-Lactamase inhibitorsMost common CTX-M, TEM and SHVMost common CTX-M, TEM and SHV
>>300300 have been identifiedhave been identifiedPlasmid-mediated, highly mobilePlasmid-mediated, highly mobile
Often associated with resistance genes to Often associated with resistance genes to aminoglycoside, TMP/SMX and tetracyclineaminoglycoside, TMP/SMX and tetracycline
Associated with fluoroquinolone resistance Associated with fluoroquinolone resistance phenotypephenotype
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Types of ESBLsTypes of ESBLs
TEMTEMSHVSHV
CTX-MCTX-MOXAOXA
Mutations
ESBL PhenotypePlasmid-mediated
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Evolution of TEM EnzymesEvolution of TEM EnzymesMIC (MIC (g/mL) ceftazidimeg/mL) ceftazidime
102102162162
TEM-1 TEM-1 0.250.25
glutamineglutamineargininearginine
TEM-12TEM-12
2.02.0
glutamineglutamineserineserine
TEM-26TEM-26
128128
lysinelysineserineserine
Fresno 11/00Fresno 11/00
EnzymeEnzyme Ceftaz Ceftaz Amino Acid PositionAmino Acid Position
MICMIC 104104 164164 240240
TEM-1TEM-1 0.12 0.12 GluGlu ArgArg GluGlu
TEM-10TEM-10 > 256 > 256 GluGlu SerSer LysLys
TEM-12TEM-12 16 16 GluGlu SerSer GluGlu
TEM-26TEM-26 256 256 LysLys SerSer GluGlu
from: Jacoby, IDCNA 11:875, 1997from: Jacoby, IDCNA 11:875, 1997
Molecular Basis of ESBLsMolecular Basis of ESBLs
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Other ESBLs
CTX-M preferentially hydrolyze CTX-M preferentially hydrolyze cefotaximecefotaxime.. - -found in strains of found in strains of Salmonella enterricaSalmonella enterrica
- -E.coli and other species ofE.coli and other species of EnterobacteriaceaeEnterobacteriaceae OXAOXA
Mainly inMainly in P.aeroginosa P.aeroginosa
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Other ESBls (cont,n)Other ESBls (cont,n)
PER-1 :Discovered in PER-1 :Discovered in P.aeruginosa P.aeruginosa (turkey)(turkey)PER-2 In south AmericaPER-2 In south America
VEB-1 VEB-1 E.coli E.coli (Vietnam) (Vietnam)CME-1 CME-1 Chrysobacterium Chrysobacterium
meningosepticummeningosepticum( Thailand)( Thailand)TLA-1 TLA-1 E.colE.coli ( Mexico )i ( Mexico )
Patrica A Cli Microbiol Rev 14; 2001Patrica A Cli Microbiol Rev 14; 2001
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ESBls are clinically ESBls are clinically importantimportant
They destroy cephalosporinsThey destroy cephalosporinsDelayed recognition and inappropriate Delayed recognition and inappropriate
treatment of sever infectiontreatment of sever infection ESBls –mediated resistance is not always ESBls –mediated resistance is not always
obvious to all cephalosporinsobvious to all cephalosporinsMany ESBL produce multi-resistant to non- Many ESBL produce multi-resistant to non- -
lactam antibiotics such as quinolons .aminoglycosides and trimethoprime
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Why is important to do special tests and Why is important to do special tests and follow complex reporting rules for ESBLsfollow complex reporting rules for ESBLs??
Why is important to do special tests and Why is important to do special tests andfollow complex reporting rules for ESBLsfollow complex reporting rules for ESBLs??
In vitro tests may be In vitro tests may be misleadingmisleading (e.g., may see (e.g., may see “S” in vitro but drug may not work!)“S” in vitro but drug may not work!)
Many types of ESBLs with varying susceptibility Many types of ESBLs with varying susceptibility profiles profiles (TEM (TEM 130; SHV 130; SHV 50; CTX-M 50; CTX-M 30) 30)
Treatment failuresTreatment failures (esp. bacteremia) when (esp. bacteremia) when patient treated with 3rd generation patient treated with 3rd generation cephalosporinscephalosporins
ESBL-producing isolates can cause ESBL-producing isolates can cause nosocomial nosocomial outbreaksoutbreaks
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Which microorganisms are ESBls Which microorganisms are ESBls positivepositive
K.pneumoniae K.pneumoniae andand K.oxytoca K.oxytocaE.coliE.coli
Enterobacter sppEnterobacter sppSalmonella sppSalmonella spp
Morganell morganii,Proteus mirabilisMorganell morganii,Proteus mirabilisSerratia marcescensSerratia marcescens
Pseudomonas aeruginosaPseudomonas aeruginosa
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ESBL TestingESBL TestingOrganisms Organisms
E. E. coli, Klebsiellacoli, Klebsiella spp., spp., Proteus mirabilisProteus mirabilis
Screen test: Screen test: Decreased Decreased
susceptibility to extended-spectrum ß-lactamssusceptibility to extended-spectrum ß-lactams
Phenotypic confirmatory test: Phenotypic confirmatory test: ß-lactam activity restored by ß-lactamase inhibitor ß-lactam activity restored by ß-lactamase inhibitor (i.e. clavulanic acid) (i.e. clavulanic acid)
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ESBLESBL Screening TestScreening Test
ESBLESBL Screening TestScreening Test
Disk zone (mm) MIC (µg/ml)Disk zone (mm) MIC (µg/ml)
**Cefpodoxime Cefpodoxime 17 17 >4 >4****
**CeftazidimeCeftazidime 22 22 >1 >1**CefotaximeCefotaxime 27 27 >1 >1 CeftriaxoneCeftriaxone 25 25 >1 >1 AztreonamAztreonam 27 27 >1 >1
* only these drugs appropriate for * only these drugs appropriate for P. mirabilisP. mirabilis**>1 **>1 g/ml for g/ml for P. mirabilisP. mirabilis
ESBL ESBL Phenotypic Confirmatory TestPhenotypic Confirmatory Test
TestTest::cefotaximecefotaxime
cefotaxime/clavulanic acidcefotaxime/clavulanic acidceftazidimeceftazidime
ceftazidime/clavulanic acidceftazidime/clavulanic acid ResultsResults::
clavulanic acid restores activity of cefotaxime or clavulanic acid restores activity of cefotaxime or ceftazidime or bothceftazidime or both
QCQC E. coliE. coli ATCC 25922; ATCC 25922; K. pneumoniaeK. pneumoniae ATCC 700603 ATCC 700603
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MIC TestMIC Testcefotaxime and ceftazidime +/- 4 μg/ml cefotaxime and ceftazidime +/- 4 μg/ml
clavulanateclavulanate::>> 33 doubling dilution decrease with either drugdoubling dilution decrease with either drug
Disk TestDisk Testcefotaxime and ceftazidime +/- 10 μg clavulanatecefotaxime and ceftazidime +/- 10 μg clavulanate
>> 55 mm zone increasemm zone increase
e.g. ceftazidime 8 μg/ml
ceftazidime + clavulanate 1 μg/ml
CLSI Confirmatory Test – CLSI Confirmatory Test – Klebsiella, E. coli, P. mirabilisKlebsiella, E. coli, P. mirabilis
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ESBL Confirmatory TestESBL Confirmatory TestPositivePositive for ESBL for ESBL
Ceftaz/CACefotax/CA
Ceftaz Cefotax
4040
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ESBL Confirmatory Test ESBL Confirmatory Test NegativeNegative for ESBL for ESBL
Ceftaz/CA Cefotax/CA
Ceftaz Cefotax
4141
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E-test for detection of ESBLsE-test for detection of ESBLs
AB Biodisk (Solna,Sweden) has introduced AB Biodisk (Solna,Sweden) has introduced a two sided ESBL E-test strip that contain a two sided ESBL E-test strip that contain either a combination of ceftazidime and either a combination of ceftazidime and ceftazidime/clavulani acid or cefotaxime ceftazidime/clavulani acid or cefotaxime and cefotaxime /clavulanic acidand cefotaxime /clavulanic acid
4343
E-test for detection ESBlsE-test for detection ESBls
Both strips have a decreasing gradient of Both strips have a decreasing gradient of ceftazidime or cefotaxime alone on one end and ceftazidime or cefotaxime alone on one end and a decreasing gradient of ceftazidime or a decreasing gradient of ceftazidime or cefotaxime plus a fixed gradient of clavulanic cefotaxime plus a fixed gradient of clavulanic acid on the other end .A>3log reduction in the acid on the other end .A>3log reduction in the MIC of cefotaxime or ceftazidime in the MIC of cefotaxime or ceftazidime in the presence of the clavulanicis considered a presence of the clavulanicis considered a
positivepositive . .
ESBL Confirmatory TestESBL Confirmatory Test
Ceftaz/CA CeftazEtest
MicroScan – ESBL panel
Vitek – confirmatory test
Vitek 2 - Advanced Expert4444
Proteus mirabilisProteus mirabilis and ESBLs and ESBLs
Not necessary to test routinelyNot necessary to test routinely
Uncommon in USAUncommon in USA
Significant problems in some locations Significant problems in some locations (e.g., Europe, South America)(e.g., Europe, South America)
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Proteus mirabilisProteus mirabilis ESBL testing ESBL testing
Routine screening not recommendedRoutine screening not recommended Perform ESBL test when clinically relevant (e.g. Perform ESBL test when clinically relevant (e.g.
bcteremiabcteremia))
--consult with medical staff to determine to testconsult with medical staff to determine to test--Practical approach ,test sterile body site isolatePractical approach ,test sterile body site isolate
Use Standard ESBLs screen test with slight Use Standard ESBLs screen test with slight modificationmodification
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Proteus mirablisProteus mirablis ESBL ESBLScreen TestScreen Test
DrugDrug Disk ScreenDisk Screen
( ( mmmm))
MIC ScreenMIC Screen
((µ g/mlµ g/ml))
CefpodoximeCefpodoxime 1717 ≥ ≥ 22**
CeftazidimCeftazidim ≤ ≤ 2222 ≥ ≥ 22
AztreonamAztreonam NANA NANA
CefotaximeCefotaxime ≤ ≤ 2727 ≥ ≥ 22
CeftriaxoneCeftriaxone NANA NANA
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Proteus mirabilisProteus mirabilis ESBLs Testing ESBLs Testing (con’t)(con’t)
Use standard disk diffusion or MIC ESBL Use standard disk diffusion or MIC ESBL phenotype confirmatory test without phenotype confirmatory test without modificationmodification
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ESBL Reporting RuleESBL Reporting RuleThe rule The rule (CLSI =NCCLS) M100-S15(CLSI =NCCLS) M100-S15…)…)
““Strains of Strains of KlebsiellaKlebsiella spp. spp. E. coli, E. coli, andand Proteus Proteus mirabilismirabilis that produce ESBLs may be clinically that produce ESBLs may be clinically resistant to therapy with penicillins, resistant to therapy with penicillins, cephalosporins, or aztreonam, despite apparent cephalosporins, or aztreonam, despite apparent
in vitro susceptibility to some of these agentsin vitro susceptibility to some of these agents”.”.The messageThe message……
Report “confirmed” ESBL-producing strains as R Report “confirmed” ESBL-producing strains as R to all to all penicillins, cephalosporins, penicillins, cephalosporins, andand aztreonam aztreonam
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If ESBL screen test is positive, must we do If ESBL screen test is positive, must we do the confirmatory test prior to reporting the confirmatory test prior to reporting
isolate as an ESBLisolate as an ESBL??
YesYes - unless you are confident that the - unless you are confident that the isolate isolate is / is not an ESBLis / is not an ESBL producer based producer based onon::
A previous isolate from the patientA previous isolate from the patient An endemic strain in your institutionAn endemic strain in your institution
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What about testing / reporting for ESBLs on What about testing / reporting for ESBLs on urine isolatesurine isolates??
The suggestion The suggestion (CLSI M100-S15)(CLSI M100-S15)……““The decision to perform ESBL screening tests on The decision to perform ESBL screening tests on all all
urine isolatesurine isolates should be made on an institutional should be made on an institutional basisbasis”.”.
RationaleRationale……-lactam concentration in bladder is very high and -lactam concentration in bladder is very high and
overcomes hydrolysis by ESBL enzymesovercomes hydrolysis by ESBL enzymesThe concernsThe concerns……
Identifying urine from acute cystitis vs. otherIdentifying urine from acute cystitis vs. other Patient with isolate from urine + other sitesPatient with isolate from urine + other sites
Infection control issuesInfection control issues5151
Will CLSI confirmatory test detect ALL ESBL-Will CLSI confirmatory test detect ALL ESBL-producing GNRproducing GNR??
No No - some isolates have - some isolates have ESBLs plusESBLs plus other resistance other resistance mechanismsmechanisms that mask ESBL detection in the that mask ESBL detection in the
confirmatory test, e.gconfirmatory test, e.g ,. ,. > >11 ESBLESBL
ESBL + ampCESBL + ampCESBL + porin mutationESBL + porin mutation
ESBLs occur in ESBLs occur in speciesspecies other than other than E. coli, KlebsiellaE. coli, Klebsiella spp., and spp., and Proteus mirabilisProteus mirabilis which CLSI does not which CLSI does not currently addresscurrently address
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ESBLs Test QC frequency Disk ESBLs Test QC frequency Disk Diffusion and MIC MethodsDiffusion and MIC Methods
Screen TestScreen Test Phenotypic ConfirmatoryPhenotypic Confirmatory
TestTest
Daily/weekly QCDaily/weekly QC
K.PneumoniaeK.Pneumoniae ATCC700603 ATCC700603
OROR
E.ColiE.Coli ATCC 25922 ATCC 25922
Daily/Weekly QCDaily/Weekly QC
K.pneumoniae ATCC 700603K.pneumoniae ATCC 700603
ANDAND
E.Coli E.Coli ATCC 25922ATCC 25922
ESBLs gene on plasmid; must store QC strain at-60ESBLs gene on plasmid; must store QC strain at-60°°C or lowerC or lower
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Microbiology Laboratories and Microbiology Laboratories and ESBLsESBLs
Unfortunately ,many clinical laboratories lack Unfortunately ,many clinical laboratories lack of understanding regarding ESBLs and Ampc ß-of understanding regarding ESBLs and Ampc ß-lactamase and their detection .This has been lactamase and their detection .This has been documented in a study in Connecticut USA, documented in a study in Connecticut USA, where it was found that 21% of laboratories where it was found that 21% of laboratories failed to detect extended –spectrum failed to detect extended –spectrum cephalosporins and Aztreonam in ESBLs and cephalosporins and Aztreonam in ESBLs and
AmpcAmpc . .
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Prevalence of ESBLsPrevalence of ESBLs
The true prevalence of ESBLs is not The true prevalence of ESBLs is not known and is probably underestimated known and is probably underestimated because of difficulties encounter in their because of difficulties encounter in their detection. However ,it is clear that ESBLs detection. However ,it is clear that ESBLs –producing organisms are distributed –producing organisms are distributed worldwide and their prevalence is worldwide and their prevalence is increasingincreasing..
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ESBls in EuropeESBls in Europe
ESBLs were first described in 1983 from ESBLs were first described in 1983 from Germany and EnglandGermany and England..In Netherlands less than 1% of In Netherlands less than 1% of E.coliE.coli and and K.pneumoniaeK.pneumoniae were ESBLs In France were ESBLs In France and Italy more than 40% strains of and Italy more than 40% strains of K.pneumoniaeK.pneumoniae resistant to Ceftazidime resistant to Ceftazidime..It is not known why the prevalence varies It is not known why the prevalence varies
so widely in closely related regionsso widely in closely related regions . .
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North AmericaNorth America
The first ESBLs –producing organisms The first ESBLs –producing organisms reported in 1988..reported in 1988..The prevalence of ESBLs production The prevalence of ESBLs production among Enterobacteriaceae in the USA among Enterobacteriaceae in the USA ranges from 0 to 25 % with the national ranges from 0 to 25 % with the national average being 3%average being 3%
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Prevalence of ESBLs USA (cont, )Prevalence of ESBLs USA (cont, )
CDC Report from ICUs(1999)CDC Report from ICUs(1999)
--E.coli E.coli 48%48%
--K.pneumoniae K.pneumoniae 10.4%10.4%
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Latin AmericaLatin America
ESBLs appear common in many Latin ESBLs appear common in many Latin Americans countriesAmericans countries..
The SENETRY study surveillance program The SENETRY study surveillance program among 10,000 bacterial from ten centers among 10,000 bacterial from ten centers showedshowed::
- - 45%45% K.pneumoniaeK.pneumoniae ESBLs positive ESBLs positive
- - 8.5%8.5% E.coliE.coli ESBLs positive ESBLs positive
6060
Asia and AustraliaAsia and Australia
The prevalence of ESBL –producing strains of The prevalence of ESBL –producing strains of Enterobacteriaceae varies fro country to country and Enterobacteriaceae varies fro country to country and from species to speciesfrom species to species.'.'
- - E.coliE.coli 5% in Korea and 23.3% in Indonesia5% in Korea and 23.3% in Indonesia .. - - Klebsiella sppKlebsiella spp 48.8% in Korea and 20-40% 48.8% in Korea and 20-40%
Southeast Asia , China and Japan .Outbreaks of Southeast Asia , China and Japan .Outbreaks of infections due to ESBls –producing organisms have been infections due to ESBls –producing organisms have been described widely in Australiadescribed widely in Australia
6161
Africa and Middle EastAfrica and Middle East
Although national surveillance are not Although national surveillance are not lacking ,outbreaks of infections due to lacking ,outbreaks of infections due to ESBL-producing organism have bee noted ESBL-producing organism have bee noted in some African nationsin some African nations,,
6262
Infection Control caused by ESBLsInfection Control caused by ESBLs
Isolation measureIsolation measure
- - private room, Private bathroomprivate room, Private bathroom
- - Contact isolation (gloves .gownContact isolation (gloves .gown..
- - Hand hygiene complianceHand hygiene compliance
- - Dedicated equipment Dedicated equipment (Thermometer, Stethoscope)(Thermometer, Stethoscope)
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Infection control(cont,)Infection control(cont,)
Identification of patientsIdentification of patients
--patients charts should be” flagged so that contact patients charts should be” flagged so that contact isolation for ESBL-colonization can be isolation for ESBL-colonization can be considered on subsequent admissions thorough considered on subsequent admissions thorough decontamination for environmental –of –care decontamination for environmental –of –care with routine low-level disinfectant (Quaternary with routine low-level disinfectant (Quaternary ammonium ,phenol)ammonium ,phenol)
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Infection Control(cont,)Infection Control(cont,)
Antibiotic UseAntibiotic Use
Antibiotic use protocol should be institute Antibiotic use protocol should be institute eliminate indiscriminate use of eliminate indiscriminate use of antibacterials and decrease selective antibacterials and decrease selective pressure for ESBLs producing strains of pressure for ESBLs producing strains of bacteriabacteria
6565
Increasing Numbers of ESBLsIncreasing Numbers of ESBLs
0
10
20
30
40
50
60
70
80
2000 2001 2002 2003 2004 2005 2006 2007
# o
f E
SBLs per year
Lewis, et al. AAC 51:4015, 2007
6666
Current ESBL Detection Current ESBL Detection Methods FailMethods Fail Routine tests are not designed for ESBL detectionRoutine tests are not designed for ESBL detection
Low level ESBL expression will not be detected by Low level ESBL expression will not be detected by current tests using low inoculumcurrent tests using low inoculum
MIC values and zone sizes of ESBL producers MIC values and zone sizes of ESBL producers overlap those of susceptible non-ESBL producersoverlap those of susceptible non-ESBL producers
ESBL double disk test may be inaccurate if ESBL double disk test may be inaccurate if positioning is suboptimalpositioning is suboptimal
ESBL breakpoint methods are limited since MICs ESBL breakpoint methods are limited since MICs for different strains can range over 7 dilutionsfor different strains can range over 7 dilutions
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Rapidly Rapidly IIncreasing ncreasing AAntibiotic ntibiotic RResistance esistance CConstitutes onstitutes OOne of the ne of the MMost ost IImportant mportant CClinical, linical, EEpidemiological and pidemiological and MMicrobiological icrobiological PProblems of roblems of TTodayoday
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