11

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

johann.pitout@cls.ab.cajohann.pitout@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

3333

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.

2222

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