1 gram negatives: mechanisms of resistance & lab detection johann dd pitout md, ff path (sa)...
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Gram negatives: Mechanisms Gram negatives: Mechanisms of Resistance & Lab detectionof Resistance & Lab detection
Johann DD Pitout MD,Johann DD Pitout MD, FF Path (SA) FF Path (SA)University of CalgaryUniversity of Calgary
Calgary Laboratory ServicesCalgary Laboratory Services
Calgary, CanadaCalgary, Canada
[email protected]@cls.ab.ca
2222
Transparency declarationTransparency declaration
Research grants from Merck Frosst, Research grants from Merck Frosst, Wyeth and Astra Zeneca Wyeth and Astra Zeneca
Speaker for Merck Frosst Speaker for Merck Frosst
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OverviewOverview
IntroductionIntroductionClones, stones and bones…Clones, stones and bones…Newer ß-lactamases Newer ß-lactamases Laboratory detectionLaboratory detectionEmergence of clones in Emergence of clones in
EnterobacteriaceaeEnterobacteriaceae SummarySummary
Am J Med 2006;119(sup1):S62-7Am J Med 2006;119(sup1):S62-700
Why Why Enterobacteriaceae?Enterobacteriaceae?NB causes of serious bacterial infections:NB causes of serious bacterial infections:
Community Community Hospital Hospital
Several species: Several species: E. coliE. coli (ExPEC) (ExPEC) K. pneumoniaeK. pneumoniaeSalmonella sppSalmonella spp
Surveillance: Surveillance: Top 5 community and hospital pathogens Top 5 community and hospital pathogens
Trends Microbiol 2006;14:413-20Trends Microbiol 2006;14:413-20
Why Resistance?Why Resistance?
Resistance is concern: Resistance is concern: 33rdrd GenCephs GenCephsCarbapenemsCarbapenemsFluoroquinolonesFluoroquinolones
Empiric treatmentEmpiric treatmentcomplicates antibiotic selectioncomplicates antibiotic selection
Inadequate initial Rx Inadequate initial Rx (AAC 07;51:1987)(AAC 07;51:1987)
risk for mortality risk for mortality health-care costs health-care costs (AAC(AAC 06;50:125706;50:1257
CMI 2007;13:1-46CMI 2007;13:1-46
What is a clone?What is a clone?
Definitions:Definitions: Isolate, strain, clone Isolate, strain, clone
Clone: Clone: Isolates with identical Isolates with identical
phenotypic+genotypic phenotypic+genotypic characteristics characteristics
Different sources/timeDifferent sources/timeTyping methods: Typing methods:
MLST MLST PFGEPFGE PCR fingerprint (MLVA) PCR fingerprint (MLVA)
clonalclonalclonalclonal
AnnRevMicro 2006;60:561-88AnnRevMicro 2006;60:561-88
MLSTMLST
Sequence variation Sequence variation Housekeeping genesHousekeeping genesEvolutionary Evolutionary
relationshiprelationshipComparing isolates Comparing isolates NOT outbreaks NOT outbreaks ST’s and CC’sST’s and CC’sE-BURSTE-BURST
NO gapA infB mdh pgi phoE rpoB tonB ST
Kp CG
3 3 1 1 1 1 18 340
Kp ON
3 4 6 1 7 4 38 147
Kp SA
2 3 1 1 1 1 48 569
CID 2007;44:418-23CID 2007;44:418-23
PFGEPFGE
Restriction of Restriction of genomic DNAgenomic DNA
Rare-cutting enzymeRare-cutting enzyme+++ discrimination+++ discriminationExcellent outbreaks Excellent outbreaks Various species Various species But not portable: But not portable:
Labour intensiveLabour intensive ? Reproducible? Reproducible Time consuming Time consuming
Dice (Tol 1.5%-1.5%) (H>0.0% S>0.0%) [0.0%-100.0%]PFGE Xba-Sbraend
10
0
95
90
85
8075
70
65
60
55
PFGE Xba-SbraendDice (Tol 1.5%-1.5%) (H>0.0% S>0.0%) [0.0%-100.0%]PFGE Xba-Sbraend
10
0
95
90
85
8075
70
65
60
55
PFGE Xba-SbraendDice (Tol 1.5%-1.5%) (H>0.0% S>0.0%) [0.0%-100.0%]PFGE Xba-Sbraend
10
0
95
90
85
8075
70
65
60
55
PFGE Xba-Sbraend
Dice (Opt:1.00%) (Tol 1.0%-1.0%) (H>0.0% S>0.0%) [0.0%-100.0%]
PFGE
100
95
90
85
80
75
70
65
60
55
50
45
PFGE
dEC1 - B12.780
dEC32
dEC35
dEC29 - B38.127
dEC36
dEC37
dEC43
dEC4 - B31.778
dEC44
dEC15 - B35.634
dEC6 - B31.899
dEC13 - B35.313
dEC31
deC11 - B34.411
dEC23 - B37.220
dEC25 - B37.293
dEC16 - B35.635
dEC27 - B37.795
dEC22 - B37.047
dEC3 - Bdyk 573
dEC2 - Bdyk 97
dEC34
dEC7 - B32.044
dEC21 - B36.564
dEC30
dEC20 - B36.446
dEC18 - B36.009
dEC19 - B36.017
dEC40
dEC14 - B35.514
dEC33
dEC5 - B31.884
dEC8 - B34.148
dEC9 - B34.159
dEC10 - B34.167
dEC38
dEC39
dEC41
dEC42
dEC45
dEC26 - B37.771
dEC24 - B37.221
dEC28 - B37.796
ST
1212 1212
Newer ß-lactamasesNewer ß-lactamasesEnzymesEnzymes InhibitedInhibited SpectrumSpectrum OrganismsOrganisms ExamplesExamples
ESBLsESBLs ClavulanateClavulanate CephalosporinsCephalosporins
PenicillinsPenicillins
Klebsiella spp.Klebsiella spp.
E. coliE. coli
TEM, SHV, TEM, SHV, CTX-MCTX-M
Plasmid-Plasmid-
AmpCsAmpCs
CloxacillinCloxacillin
Boronic acidBoronic acid
Cephalosporins Cephalosporins CephamycinsCephamycins
Klebsiella spp.Klebsiella spp.
E. coliE. coli
Salmonella spp.Salmonella spp.
CMY, FOX CMY, FOX
MBLsMBLs
(CHE-B)(CHE-B)
EDTAEDTA CarbapenemsCarbapenems
CephalosporinsCephalosporins
P. aeruginosaP. aeruginosa
Klebsiella sppKlebsiella spp
E. coli E. coli
IMP, VIM, IMP, VIM, NDMNDM
KPC’sKPC’s
(CHE-A)(CHE-A)
ClavulanateClavulanate
Boronic acidBoronic acid
CarbapenemsCarbapenems
CephalosporinsCephalosporins
Klebsiella spp.Klebsiella spp.
E. coliE. coli
KPCKPC
1313
Clinical Case no 1Clinical Case no 1
3 month girl with diarrhoea 3 month girl with diarrhoea Watery with mucusWatery with mucusAbnormal growth parametersAbnormal growth parametersAdmitted and Rx Admitted and Rx Previous diarrhoea Previous diarrhoea
Other family membersOther family membersOlder sister and DadOlder sister and Dad
Salmonella entericaSalmonella enterica serotype Newport serotype Newport
1414
Salmonella spp.Salmonella spp.
SusceptibilitySusceptibility CFZ >64CFZ >64 TZP >64/4TZP >64/4 CAZ 16CAZ 16 CRO 16CRO 16 FOX >64FOX >64 FEP <16FEP <16 ATM 16ATM 16 CIP <0.25CIP <0.25 GEN <8GEN <8 IPM <2 IPM <2
CLSI ESBL confirmation test:
CAZ 12mm CAZ + CLAV 15mm CTX 16mm CTX + CLAV 16mm
Neg ESBL test
1515
CTT CTT
+PBA
1616ClinMicroRev 09;22:161-82ClinMicroRev 09;22:161-82
AmpC ß-lactamases
Chromosomal Organisms:
Enterobacter, Serratia,
Citrobacter, Pseudo.
cephalosporinases inducible not inhibited by c,t,s eg.: AmpC
Plasmid Organisms:
Klebsiella, P. mirabilis, Salmonella spp.
cephalosporinases constitutive/inducible not inhibited by c,t,s eg.: CMY, FOX,
DHA, ACC
17171717DMID 01;41:57-61DMID 01;41:57-61
E. coliE. coli and AmpC’s and AmpC’s
Weak promoterWeak promoter
Strong attenuatorStrong attenuator
Plasmid-mediated AmpCPlasmid-mediated AmpC
mutations
18181818ClinMicroRev 09;22:161-82ClinMicroRev 09;22:161-82
Plasmid-mediated AmpC’s Plasmid-mediated AmpC’s
R to cephamycinsR to cephamycins some cephalosporins, some cephalosporins,
penicillinspenicillins NotNot carbapenems carbapenems
MultiresistantMultiresistantOrganisms: Organisms: K. K.
pneumoniae,pneumoniae, E. coli, E. coli, Salmonella sppSalmonella spp
OriginOriginExtended-spectrum Extended-spectrum
cephs cephs
1919ERAIT 08;6:657-69ERAIT 08;6:657-69
Laboratory detectionLaboratory detection
No guidelinesNo guidelines Not all cephamycin/3Not all cephamycin/3rdrd GC R = AmpC GC R = AmpC Phenotypic tests Phenotypic tests
Inhibitor-based approaches Inhibitor-based approaches Disks: boronic acid and othersDisks: boronic acid and others AmpC E-test: cloxacillin AmpC E-test: cloxacillin
Multiplex PCR Multiplex PCR
2020
F ig 2. D etection of AmpC s
E. coli, Klebsiella spp, P.mirablis, Salmonella spp
Screen positive (Vitek 2)• FOX >16ug/ml
AmpC disk confirmation test:• CTT and CTT with PBA
NB. If an organism test positive for an AmpC and ESBL, it should be sent for a MDDT ESBL test. This is to check if the AmpC is giving a false positive ESBL test. If MDDT is positive, consult the MOC on how to report. If MDDT is negative report that the organism only produce an AmpC.
F ig 2. D etection of AmpC s
E. coli, Klebsiella spp, P.mirablis, Salmonella spp
Screen positive (Vitek 2)• FOX >16ug/ml
AmpC disk confirmation test:• CTT and CTT with PBA
NB. If an organism test positive for an AmpC and ESBL, it should be sent for a MDDT ESBL test. This is to check if the AmpC is giving a false positive ESBL test. If MDDT is positive, consult the MOC on how to report. If MDDT is negative report that the organism only produce an AmpC.
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Clinical case no 2Clinical case no 2
47 yr F with recent travel47 yr F with recent travelER with fever, dysuria, frequency ER with fever, dysuria, frequency Exam: Exam:
T 39.2ºC T 39.2ºC supra-pubic and renal tendernesssupra-pubic and renal tenderness
Diagnosis of UTI Diagnosis of UTI 2 sets of BC, urine2 sets of BC, urine
Rx ciprofloxacin, referred to HPTP Rx ciprofloxacin, referred to HPTP Next day blood cultures positiveNext day blood cultures positive
2323
Escherichia coliEscherichia coli
SusceptibilitySusceptibility CFZ >64CFZ >64 TZP 64/4TZP 64/4 CAZ 16CAZ 16 CRO >32CRO >32 FOX <8FOX <8 FEP 16FEP 16 ATM 16ATM 16 CIP >4CIP >4 GEN >16GEN >16 IPM <2 IPM <2
CLSI ESBL CLSI ESBL confirmation test:confirmation test:
CAZ 22mm CAZ + CLAV 23mm
CTX 8mm CTX + CLAV 20mm
Pos ESBL test
2424AmJMed 97;103:51-9AmJMed 97;103:51-9
Extended-spectrum ß-lactamasesExtended-spectrum ß-lactamases
Early 1980’s Early 1980’s World-wide World-wide Hydrolyse:Hydrolyse:
cephalosporins, cephalosporins, penicillins, monobactpenicillins, monobact
not:not: cephamycins, cephamycins, carbapenemscarbapenems
Inhibitor sensitiveInhibitor sensitive clav, sulb, tazoclav, sulb, tazo
TypesTypesEnterobacteriaceaeEnterobacteriaceaeClinically relevantClinically relevant
CLSI guidelines CLSI guidelines 20102010
MIC ≥ 1 CTX/CRO ≥ 2 CAZ MIC ≥ 1 CTX/CRO ≥ 2 CAZ Zone ≤ 26mm CTX, ≤ 23mm CRO, ≤ 21mm CAZ Zone ≤ 26mm CTX, ≤ 23mm CRO, ≤ 21mm CAZ
No confirmatory test for therapy No confirmatory test for therapy
butbutuseful for infection control/epidemiology useful for infection control/epidemiology
2626
Detection of ESBLsDetection of ESBLs
E. coli, Klebsiella spp, P.mirablis, Salmonella spp
All other Enterobacteriaceace
CLSI Screen positive • CRO: 1ug/ml and• CAZ: 1ug/ml
Modified double diskFEP + CLAV
CLSI ESBL disk confirmation test:
• CTX and CTX with Clav• CAZ and CAZ with Clav
CLSI Screen positive • CRO: 1ug/ml and• CAZ: 1ug/ml
Clinical case no 3Clinical case no 3
32yr M travelled in Southern India32yr M travelled in Southern IndiaAdmitted Admitted city Mysore: city Mysore:
HHyperglycemiayperglycemiaDeveloped upper UTIDeveloped upper UTIRx with CiprofloxacinRx with Ciprofloxacin
Transferred to AlbertaTransferred to AlbertaUpper UTI and prostatitisUpper UTI and prostatitisRx with ERTRx with ERT
2828
Escherichia coli Escherichia coli (MH01)(MH01)
SusceptSuscept CFZ >64CFZ >64 TZP >64/4TZP >64/4 CAZ >64CAZ >64 CRO >64CRO >64 FOX >64FOX >64 FEP >64FEP >64 ATM >64ATM >64 CIP >8CIP >8 GEN >16GEN >16 IPM 16 IPM 16
ESBL confirmation: CAZ 6mm CAZ + CLAV 6mm CTX 6mm CTX + CLAV 6mm
AmpC boronic test: CTT 6mm CTT + PBA 6mm ERT 6mm
ClinMicroRev 2005;18:306-25ClinMicroRev 2005;18:306-25
Class B CHE’sClass B CHE’s
Metallo-Metallo-ß-lactamases ß-lactamases (MBLs)(MBLs)
Active site: Zn+Active site: Zn+ Inhibited by EDTAInhibited by EDTA R to all R to all ß-lactams except:ß-lactams except:
monobactams monobactams Chromosomal (Steno)Chromosomal (Steno) Types: IMP, VIM, SPM, Types: IMP, VIM, SPM,
GIM, SIM, AIGIM, SIM, AIM, KHM, M, KHM, DIM, DIM, NDMNDM
JAC 2011;66:689-92JAC 2011;66:689-92
NDM NDM ß-lactamasesß-lactamases
11stst report from Sweden report from Sweden (AAC 2009;53:5046-54)(AAC 2009;53:5046-54)
WorldwideWorldwideWidespread in Subcontinent Widespread in Subcontinent (Lancet ID 2010 10;597-602)(Lancet ID 2010 10;597-602)
India, Pakistan, Bangladesh India, Pakistan, Bangladesh Associated with travel (medical tourism)Associated with travel (medical tourism)Organisms:Organisms:
E. coli E. coli (community) (community) KlebsiellaKlebsiella spp. (hospital) spp. (hospital)
MultiR MultiR ? Fatal cases ? Fatal cases
3232
Clinical case no 4Clinical case no 4
CAP external quality assurance programCAP external quality assurance programKlebsiella pneumoniaeKlebsiella pneumoniaeUrine; significant colony count Urine; significant colony count Adult Diabetic patientAdult Diabetic patientNeurogenic bladderNeurogenic bladder ICU for 2 weeksICU for 2 weeksRecently hospitalised in New YorkRecently hospitalised in New York
3333
Klebsiella pneumoniaeKlebsiella pneumoniae
SusceptibilitySusceptibility CFZ >64CFZ >64 TZP >64/4TZP >64/4 CAZ >64CAZ >64 CRO >64CRO >64 FOX >64FOX >64 FEP 16FEP 16 ATM >64ATM >64 CIP >8CIP >8 GEN >16GEN >16 IPM 2 IPM 2
ESBL confirmation: CAZ 10mm CAZ + CLAV 13mm CTX 11mm CTX + CLAV 14mm
AmpC boronic test: CTT 10mm CTT + PBA 22mm ERT 6mm
3535
Class A CHEsClass A CHEs
Different types (e.g.SME) Different types (e.g.SME) KPC ß-lactamases KPC ß-lactamases KK. . ppneumoniaeneumoniae
CCarbapenemasearbapenemase11stst reported late 1990’s reported late 1990’s
North CarolinaNorth CarolinaHydrolyze all ß-lactamsHydrolyze all ß-lactams
Including carbapenemsIncluding carbapenems Inhibited by clavulanate Inhibited by clavulanate Types: KPC 2-???Types: KPC 2-???Klebsiella Producing Chaos
Lancet Infect Dis 2009;9:228-36Lancet Infect Dis 2009;9:228-36
CLSI June 2010CLSI June 2010
Carbapenemases & EnterobacteriaceaeCarbapenemases & Enterobacteriaceae
MIC ≥ 0.25 ERT, ≥ 1 IPM/MER/DOR MIC ≥ 0.25 ERT, ≥ 1 IPM/MER/DOR Zone ≤ 22 mm ERT/IPM/MER/DOR Zone ≤ 22 mm ERT/IPM/MER/DOR
No confirmatory test for therapy if No confirmatory test for therapy if I or R to I or R to allall carbapenems tested carbapenems tested
butbutOK for infection control/epidemiology OK for infection control/epidemiology
F ig 4 . D e te c tio n o f C a rb a p e n e m a s e sin E n te ro b a c te r ia c e a e
E n te ro b a c te r ia c e a e
S c re e n p o s it ive ( V ite k 2 )• E R T > 1 u g /m l
C L S I M o d if ie d H o d g e te s t
K P C P C R
If p o s it ive
F ig 4 . D e te c tio n o f C a rb a p e n e m a s e sin E n te ro b a c te r ia c e a e
E n te ro b a c te r ia c e a e
S c re e n p o s it ive ( V ite k 2 )• E R T > 1 u g /m l
C L S I M o d if ie d H o d g e te s t
K P C P C R
If p o s it ive
++false positives with ERTUse MER
Multiplex PCR
>0.25
Multiplex PCRMultiplex PCR
EuroSurveill 2010;15:piiEuroSurveill 2010;15:pii
40404040Curr Opin Microbiol 2006;9:466-75Curr Opin Microbiol 2006;9:466-75
CTX-M CTX-M ß-lactamasesß-lactamases
Active Active CCeftoeftoTTaaXXime 1ime 1stst MMunich unich activity CTX activity CTX by tazobactamby tazobactam 40% similarity to SHV/TEM40% similarity to SHV/TEM Originate fromOriginate from Kluyvera Kluyvera spp.spp. Insertion element: ISInsertion element: ISEcp1Ecp1 Divided into 5 groupsDivided into 5 groups
Groups 1, 2, 8, 9, 25Groups 1, 2, 8, 9, 25
4141
CTX-M-type ESBLs: first reports 1989
1989Matsumoto et al. AAC 1988; 32:1243
Bauernfeind et al. Infection 1990; 18:294Power et al. AAC 2002; 46:602
1986
1990s
4242Lancet Infec Dis 08;8:159-66Lancet Infec Dis 08;8:159-66
The CTX-M pandemic: since 2000
4343Lancet Infec Dis 08;8:159-66Lancet Infec Dis 08;8:159-66
The CTX-M-15 pandemic: since 2003
4444
Dissemination of CTX-M-15Dissemination of CTX-M-15
MLST profile ST131MLST profile ST131 Broadly disseminated Broadly disseminated Homogenous virulence Homogenous virulence
genotypegenotype IncF group plasmidsIncF group plasmids
3 different profiles 3 different profiles OXA-1, aac(6)-Ib-cr, OXA-1, aac(6)-Ib-cr,
TEM-1TEM-1
JAC 08;61:273-81, EID 08;14:195-200JAC 08;61:273-81, EID 08;14:195-200
4545IJAA 10; 35:316-21IJAA 10; 35:316-21
The clone ST131 pandemic: since 2006
4646AAC 10;54:1327-30AAC 10;54:1327-30
0
5
10
15
20
25
30
35
Bram Edm MedH MtSinai
Montr Reg Otta Winn Van Vic Calg Chica
No
of
Ca
se
s
NonST131 ST131
MLST clone ST131MLST clone ST131(96/209 [46%])(96/209 [46%])
47474747
E. coliE. coli from blood from blood
0
100
200
300
400
500
600
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
0
5
10
15
20
25
30
35
40
45
50
E.coli ESBLs
4848
05
101520253035404550
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
No
of
case
s
Non-ST131 ST131
Distribution of ST131Distribution of ST131(69/134[51%])(69/134[51%])
AAC 09;53:2846-51AAC 09;53:2846-51
4949AAC 09;53:2846-51AAC 09;53:2846-51
Characteristics of ST131Characteristics of ST131
Characteristic ST131 [no (% )]
Non-ST131 [no (% )]
p-value
Antimicrobial susceptibilities: GEN resistance TOB resistance SXT resistance TZP resistance CIP resistance
18/21 (86%) 18/21 (86%) 14/21 (67%) 17/21 (81%)
21/21 (100%)
22/46 (48%) 29/46 (63%) 30/46 (65%) 14/46 (30%) 39/46 (85%)
0.004 0.09 1.0
0.0002 0.004
PM QR determinants: aac(6’)-Ib-cr
18/21 (86%)
6/46 (13%)
<0.0001
Acquisition: Hospital-acquired Health-care associated Community-acquired
0/21 (0%)
8/21 (38%) 13/21 (62%)
16/46 (35%) 15/46 (33%) 15/46 (33%)
0.006
Focus: Urosepsis Intra abdominal infections Respiratory infections Primary bacteraemia
18/21 (86%)
0/21 (0%) 1/21 (5%)
2/21 (10%)
26/46 (57%) 14/46 (30%)
2/46 (4%) 4/46 (9%)
0.04
5050IJAA 10;35:316-21IJAA 10;35:316-21
ST131
CTX-M-15
What makes ST131 so special?What makes ST131 so special?
• Uropathogenic
• Phylo B2
• Certain VF’s
• Adherence
• IncF plasmids
• R factors
• Addiction systems
CTX-M ESBLsCTX-M ESBLs
KluyveraKluyvera spp spp E. coliE. coliCTX-M-1CTX-M-1
CTX-M-15CTX-M-15
ST131
ISISEcp1Ecp1
5252
Significance of KPCsSignificance of KPCs
Multiple R (Rx options very limited)Multiple R (Rx options very limited)Nosocomial clonal outbreaks Nosocomial clonal outbreaks
Inter-hospital, inter-city, inter-country Inter-hospital, inter-city, inter-country
Infections Infections Systemic (invasive devices)Systemic (invasive devices)UTIs (indwelling catheters)UTIs (indwelling catheters)
Not only in Not only in K. pneumoniaeK. pneumoniae BSIs BSIs ↑↑ mortality mortality (Infect Control Hosp Epidemiol. 2010 Oct 25)(Infect Control Hosp Epidemiol. 2010 Oct 25)
Lancet Infect Dis 2009;9:228-36Lancet Infect Dis 2009;9:228-36
5353Lancet Infect Dis 2009;9:228-36Lancet Infect Dis 2009;9:228-36
ST258ST258
FEMSMicroReviews 2011 Feb 9FEMSMicroReviews 2011 Feb 9
KPC and clones KPC and clones
ST258 ST258 40% of KPC’s40% of KPC’s CTX-M-14 CTX-M-14
Hypervirulent cloneHypervirulent cloneOther STsOther STs
ST438 (Brazil)ST438 (Brazil)
Also: Also: Mobile elements Mobile elements
(Tn4401)(Tn4401) PlasmidsPlasmids
KPC’sKPC’s
Environmental bug K. pneumoniaeKPC-2
Tn4401Tn4401
KPC-2/3KPC-2/3
ST258
JAC 2011;66:689-92JAC 2011;66:689-92
Worldwide distribution of NDMsWorldwide distribution of NDMs
Cricket WC
JAC 2011;66:689-92JAC 2011;66:689-92
NDMs and clones NDMs and clones
K. pneumoniaeK. pneumoniaeNot clonally relatedBroad-host range plasmidse.g. A/C, N
E. coli Clonal ST101 (Canada, UK, Europe, Australia)ST131 USA (scary)
What makes a clone….What makes a clone….
International clonesInternational clones Virulence Virulence Adherence factorsAdherence factors
Plasmids Plasmids Narrow host range Narrow host range Broad host range Broad host range
Clones use plasmids Clones use plasmids and plasmids use clones and plasmids use clones
Plasmids as per Plasmids as per BioShock: “giving the BioShock: “giving the user what some might user what some might call call super powers"super powers"
5959
MLST clone ST131MLST clone ST131
Understanding how ST131 has emerged Understanding how ST131 has emerged and successfully disseminated within the and successfully disseminated within the hospital and community, including across hospital and community, including across national boundaries, should be a public national boundaries, should be a public health priorityhealth priority
Neil Woodford, UKNeil Woodford, UK
JAC 2008;61:233-4JAC 2008;61:233-4
6060
AcknowledgementsAcknowledgements
University of Calgary:
• K. Laupland
• D. Church
• D. Gregson
Calgary Lab Services:
• L. Campbell
• B. Chow
• G. Peirano
NML:
• M. Mulvey
• D. Boyd
Special Mention:
L. Poirel, K. Thomson, N. Hanson, E. S-Molland, J. Johnson, D. Guttman