E. coli

conference.cast.com

E. coli

ß-lactamase producing bacteria

in the community setting:

Clonal Wars

Johann DD Pitout MD, FF Path (SA)

University of Calgary

Calgary Laboratory Services

Calgary, Canada

johann.pitout@cls.ab.ca

1


Transparency declaration

Research grants from Merck Frosst,

Wyeth and Astra Zeneca

Speaker for Merck Frosst

2


Clones and typing

Overview

Newer ß-lactamases

Extended-spectrum ß-lactamases

Metallo-ß-lactamases

NDMs

Management of patients

Summary

3


What is a clone?

CMI 2007;13:1-46

Definitions:

Isolate, strain, clone

Clone:

Isolates with identical

phenotypic+genotypic

characteristics

Different sources/time

Typing method:

PFGE

MLST

MLVA

4


clonal

5


Dice (Tol 1.5%-1.5%) (H>0.0% S>0.0%) [0.0%-100.0%]

PFGE Xba-Sbraend

55 55 55

60 60 60

65 65 65

70 70 70

75 75 75

80 80 80

85 85 85

90 90 90

95 95 95

100 100 100

PFGE Xba-Sbraend

PFGE

CID 2007;44:418-23

Restriction of

genomic DNA

Rare-cutting enzyme

+++ discrimination

Excellent outbreaks

Various species

But not portable:

Labour intensive

? Reproducible

Time consuming

6


MLST

AnnRevMicro 2006;60:561-88

Sequence variation

Housekeeping genes

ST’s and CC’s

E-BURST

Evolutionary

relationship

Comparing isolates

NOT outbreaks

7


Dice (Opt:1.00%) (Tol 1.0%-1.0%) (H>0.0% S>0.0%) [0.0%-100.0%]

PFGE

45

50

55

ST

60

65

70

75

80

85

90

95

100

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


Newer ß-lactamases

Enzymes Inhibited Spectrum Organisms Examples

ESBLs Clavulanate Cephalosporins

Plasmid-

AmpCs

MBLs

(CHE-B)

KPC’s

(CHE-A)

Cloxacillin

Boronic acid

Penicillins

Cephalosporins

Cephamycins

EDTA Carbapenems

Clavulanate

Boronic acid

Cephalosporins

Carbapenems

Cephalosporins

Klebsiella spp.

E. coli

Klebsiella spp.

E. coli

Salmonella spp.

P. aeruginosa

Klebsiella spp

E. coli

Klebsiella spp.

E. coli

TEM, SHV,

CTX-M

CMY, FOX

IMP, VIM,

NDM

KPC

9 9


Clinical case no 1

47 yr F with recent travel

ER with fever, dysuria, frequency

Exam:

T 39.2ºC

supra-pubic and renal tenderness

Diagnosis of UTI

2 sets of BC, urine

Rx ciprofloxacin, referred to HPTP

Next day blood cultures positive

10


Susceptibility

CFZ >64

TZP 64/4

CAZ 16

CRO >32

FOX 4

GEN >16

IPM


Extended-spectrum ß-lactamases

AmJMed 97;103:51-9

Early 1980’s

World-wide

Hydrolyse:

cephalosporins,

penicillins, monobact

not: cephamycins,

carbapenems

Inhibitor sensitive

clav, sulb, tazo

Types

Enterobacteriaceae

Clinically relevant

12


Population-based surveillance

2000-2

E. coli (>95% ESBLs)

ESBLs

Non-CTX-M: 47 (30%)

27 (57%) from community

CTX-M: 110 (70%)

84 (76%) from community

CID 04;38:1736-41

UTIs

13


CTX-M ß-lactamases

Active CeftoTaXime 1 st Munich

activity CTX

by tazobactam

40% similarity to SHV/TEM

Originate from Kluyvera spp.

Insertion element: ISEcp1

Divided into 5 groups

Groups 1, 2, 8, 9, 25

Curr Opin Microbiol 2006;9:466-75

14


The CTX-M pandemic: since 2000

Lancet Infec Dis 08;8:159-66

15


The CTX-M-15 pandemic: since 2003

Lancet Infec Dis 08;8:159-66

16


The clone ST131 pandemic: since 2006

IJAA 10; 35:316-21

17


No of Cases

35

30

25

20

15

10

5

0

Bram Edm MedH Mt

Sinai

MLST clone ST131

(96/209 [46%])

Montr Reg Otta Winn Van Vic Calg Chica

NonST131 ST131

AAC 10;54:1327-30 IJAA 10;36:19-23

18


600

500

400

300

200

100

0

E. coli from blood

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

E.coli ESBLs

50

45

40

35

30

25

20

15

10

5

0

19


No of cases

50

45

40

35

30

25

20

15

10

5

0

Distribution of ST131

(69/134[51%])

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

Non-ST131 ST131

AAC 09;53:2846-51

20


Characteristics of ST131

Characteristic ST131

[no (% )]

Antimicrobial susceptibilities:

GEN resistance

TOB resistance

SXT resistance

TZP resistance

CIP resistance

PM QR determinants:

aac(6’)-Ib-cr

Acquisition:

Hospital-acquired

Health-care associated

Community-acquired

Focus:

Urosepsis

Intra abdominal infections

Respiratory infections

Primary bacteraemia

18/21 (86%)

18/21 (86%)

14/21 (67%)

17/21 (81%)

21/21 (100%)

18/21 (86%)

0/21 (0%)

8/21 (38%)

13/21 (62%)

18/21 (86%)

0/21 (0%)

1/21 (5%)

2/21 (10%)

AAC 09;53:2846-51

Non-ST131

[no (% )]

22/46 (48%)

29/46 (63%)

30/46 (65%)

14/46 (30%)

39/46 (85%)

6/46 (13%)

16/46 (35%)

15/46 (33%)

15/46 (33%)

26/46 (57%)

14/46 (30%)

2/46 (4%)

4/46 (9%)

p-value

0.004

0.09

1.0

0.0002

0.004


Virulence and ST131

ST131

CID 10;51:286-94

127 E. coli, 2007

Sentry & Mystic

54 (17%) ST131

70% of FQ-Res

Phylogenetic B2

VF profile

Success of ST131

Resistance

VFs

22


Plasmids and ST131

AAC 10;53:4472-82

Sequenced 3 plasmids

lineages ST131

2 CTX-M-15

1 CTX-M-3

IncFII plasmids with

bla CTX-M-15 bla OXA-1,

bla TEM-1, tetA, aac(6’)-Ibcr,

and aac(3)-II

Multiple addiction

systems

Essential role in rapid

spread

23


CTX-M ESBLs

ISEcp1

Kluyvera spp E. coli

CTX-M-1

ST131 (ciproR)

CTX-M-15

24


ESBLs 20 th Cen

Organism:

Klebsiella spp

SHV + TEM

Nosocomial

Susceptibilities

multi-R

Mol epidemiology

clonally related

Characteristics

ClinMicroRev 05;18:657-86,

LancetInfectDis 08;8:59-66

ESBLs 21 st Cen

Organism:

E. coli

CTX-M

Community-onset

Susceptibilities

multi-R (CiproR)

Mol epidemiology

ST 131

25


Primary

Clinical presentations

Hospital-onset

Respiratory tract

(HAP, VAP)

Abdominal

Blood stream (sepsis)

SST infections

Urinary tract

Miscellaneous

ClinMicroRev 05;18:657-86, CMI

08;14(S1):104-10, ERAIT 08;6:671-83

Community-onset

Urinary tract

Urosepsis

Abdominal

Biliary

Miscellaneous

(meningitis)

26


Hospital-onset

Antibiotic exposure

Recent surgery

Instrumentation

Admission to ICU

Long hospital stay

Nursing home

Underlying disease

Diabetes mellitus

Malignancy

Risk factors

ERAIT 08;6:671-83, JInfect 08;57:441-8

Community-onset

Urinary tract

Repeat UTIs

Instrumentation

Previous antibiotics

Nursing home

Older M/F

Underlying disease

Diabetes mellitus

Malignancy

Travel

27


Clinical case no 2

32yr M travelled in Southern India

Admitted city Mysore:

Hyperglycemia

Developed upper UTI

Rx with Ciprofloxacin

Transferred to Alberta

Upper UTI and prostatitis

Rx with ERT

28


Escherichia coli (MH01)

Suscept

CFZ >64

TZP >64/4

CAZ >64

CRO >64

FOX >64

FEP >64

ATM >64

CIP >8

GEN >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

29


Class B CHE’s

ClinMicroRev 2005;18:306-25

Metallo-ß-lactamases

(MBLs)

Active site: Zn+

Inhibited by EDTA

R to all ß-lactams except:

monobactams

Chromosomal (Steno)

Types: IMP, VIM, SPM,

GIM, SIM, AIM, KHM, DIM,

NDM

31


NDM ß-lactamases

1 st report from Sweden (AAC 2009;53:5046-54)

Worldwide

Widespread in Subcontinent (Lancet ID 2010 10;597-602)

India, Pakistan, Bangladesh

Associated with travel (medical tourism)

Organisms:

E. coli (community)

Klebsiella spp. (hospital)

MultiR (S to COL, TIG, FOS)

Fatal cases (?Belgium)

JAC 2011;66:689-92

32


Worldwide distribution of NDMs

JAC 2011;66:689-92

33


NDM E. coli pandemic: ? clonal

ST101 ST131

EID 2011;17:242-4, AAC 2011;54:4914-6

34


Plasmid

Klebsiella spp + others

Broad-host range plasmids

e.g. A/C, N

Hospital associated

NDM-pandemic

Clonal

E. coli (ST101, 131)

Narrow-host range plasmids

e.g. F

Community-onset

35


Change management

Clinical Microbiology Laboratory

ESBL and CHE testing

Clinician

Rx of community-associated infections

UTIs or intra-abdominal infections

Infection control practitioner

Prevent the spread

Infect Med 07;24:57-65

36


MLST clone ST131

Understanding how ST131 has emerged

and successfully disseminated within the

hospital and community, including across

national boundaries, should be a public

health priority

VIM + ?KPC ST131

JAC 2008;61:233-4

Neil Woodford, UK

37

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