Epidemiology of ESBL in

hospitals and in the community

Dietrich Mack

Chair of Medical Microbiology and Infectious Diseases

The School of Medicine - University of Wales Swansea

P R I F Y S G O L C Y M R U A B E R T A W E

U N I V E R S I T Y O F W A L E S S W A N S E A

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Outbreak with Klebsiella pneumoniae

(SHV-5)

Location:

Surgical ICU of university hospital

with busy liver transplantation unit

Patients: 11

Duration:

Interventions:

Termination:

5 months

Contact isolation and single rooms

without success

Closure of ICU and dedication of a

peripheral ward with specific

health care personal for ESBLpatients

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ESBL-positive strains detected in resistance

studies of the Paul-Ehrlich-Gesellschaft

14

Percentage of ESBL-positive

12

10

8

6

4

2

0

1995 1998 2001 2004

E. coli K. pneumoniae K. oytoca

http://www.p-e-g.org/ag_resistenz/PEG-Resistenzstudie%202004.pdf

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Molecular types of ESBLs isolated

in Hamburg 1998 - 2001

CTX-M SHV TEM

E. coli 2 5 1

K. pneumoniae - 20 1

K. oxytoca 2 1 -

All 4 26 2

Stürenburg 2003 Diagn. Microbiol. Infect. Dis. 45:29

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ESBL types in enterobacteria of multi-centre

study Cologne, Heidelberg, Hamburg 2005

CTX-M SHV TEM

E. coli 34 2 3

K. pneumoniae 11 12 -

K. oxytoca 4 1 -

Enterobacter spp. 6 6 -

Proteus mirabilis 3 - 1

All 58 21 4

Wiegand 2007 J Clin Microbiol 45:1167

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ESBL resistance mechanisms among

cephalosporin-resistant Enterobacteriaceae in

London and South-East England 2004

Species N CTX-M (%) Other ESBL (%) AmpC (%)

Escherichia coli 574 291 (50.7) 88 (15.3) 41 (7.1)

Klebsiella spp. 243 198 (81.5) 24 (9.9) 1

Enterobacter spp. 201 8 (4.0) 26 (12.9) 90 (44.8)

Estimate 2.5% of all E. coli isolates are cephalosporin

resistant; 1.1% of all carry CTX-M enzymes

9.7% of all Klebsiella spp. isolates are cephalosporin resistant;

7.6% of all carry CTX-M or other ESBL

Potz 2006 JAC 58:320

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Emergence of CTX-M-positive

Enterobacteriaceae in Austria

Percentage of CTX-M-positive strains

90

80

70

60

50

40

30

20

10

0

1998 1999 2000 2001 2002 2003 2004

E. coli Klebsiella spp.

Eisner et al 2006 AAC 50:785

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Trends in production of ESBLs among

Enterobacteriaceae in Italy

Inpatients

Outpatients

2003 1999 2003

% Total In species Total In species Total In species

Escherichia coli 31.9 4.4 10.8 1.2 34.2 1.9

Proteus mirabilis 26.2 25.7 25.7 16.3 39.2 14.8

Providencia stuartii 7.1 36.7 5.3 28.1 10.1 13.8

Klebsiella pneu. 15.1 10.2 37.1 20.0 6.3 2.6

Klebsiella oxytoca 3.4 8.0 4.9 15.1 1.3 3.2

Enterobacter aerog 7.5 17.9 6.0 20.5 5.1 8.3

Luzzaro 2006 JCM 44.1659

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Long-term study of ESBL epidemiology

in Escherichia coli in Sevilla, Spain

Romero 2005 CMI 11:625

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Dissemination of CTX-M type ESBL in

Enterobacteriaceae in People‘s Republic of China

Munday 2004 Int J Antimicrob Agents 23:175

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Characteristics of CTX-M producing E. coli in

the Calgary Health Region 2000 to 2005

Pitout 2007 AAC 51:1281

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Epidemiology of CTX-M-producing

Escherichia coli strains in the UK 2003/2004

Woodford 2004 JAC 54:735

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Distribution of episodes of bacteraemia due to

ESBL-producing Escherichia coli

Rodriguez-Bano 2006 CID 43:1409

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Number of ESBL-positive E. coli and

Klebsiella spp. bacteraemia cases

Number of bacteraemic episodes

18

16

14

12

10

8

6

4

2

0

8.4% 26.5% 0.5% 22.6%

2007 2006 2005

E. coli Klebsiella spp.

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Proportion of community-onset and hospitalacquired

episodes of ESBL-positive E. coli and

Klebsiella spp. bacteraemia

Number of ESBL-positive episodes

25

20

15

10

5

0

27.6% 26.6% 22.2%

2007 2006 2005

CA

HAI

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Risk factors for blood stream infection with

ESBL-positive E. coli and Klebsiella spp.

OR P value

Prior ß-lactam antibiotics 10.86 .003

Other antibiotics 7.50 .03

Prior admission to ICU 6.0 .006

Length of hospital stay > 15 d 2.79 .01

Skippen et al. 2006 J Hosp Infect 64:115

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Community-onset urinary tract infection caused by

CTX-M-positive Escherichia coli in Truro, Cornwall

• 69 resistant E. coli strains submitted to reference laboratory

during 2004 - 2005

• Clonal typing identified CTX-M-group 1 positive outbreak

strain different from UK epidemic strain A (CTX-M-15)

• „Cornish“ outbreak strain caused hospital acquired blood

stream infection (patient 1) and mostly community-onset UTI

• Most patients had hospital contact during the preceding 3

months during period of admission of patient 1

Woodford 2004 JAC 54:735

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Independent risk factors for community acquired

ESBL-positive urinary tract infections

Risk factor OR 95% CI

Previous hospitalisation < 3 mo 8.95 3.77 – 21.25

Antibiotic treatment < 3 mo 3.23 1.76 – 5.91

Age > 60 yr 2.65 1.45 – 4.83

Diabetes 2.57 1.20 – 5.51

Male gender 2.47 1.22 – 5.01

Klebsiella pneumoniae infection 2.31 1.17 – 4.54

Previous use of 2nd gen ceph 15.8 1.7 – 143

Previous use of 3rd gen ceph 10.1 4.2 – 24.0

Previous use of quinolones 4.1 1.8 – 9.0

Previous use of penicillin 4.0 1.6 – 9.0

Colodner 2004 Eur J Clin Microbiol Infect Dis 23:163

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Faecal carriage of ESBL positive

Enterobacteriaceae

England 2004 1.9%

Spain 2001/2002 2.1% – 7.5%

Spain 1991 0.3% – 0.7%

2003 5.5% - 11.8%

Munday et al. 2004 JAC 54:628

Miro 2005 JAC 56:1152

Valverde 2004 JCM 42:4769

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Persistent recovery of ESBL-positive Escherichia

coli with CTX-M-14/17 and TEM-35 from farm

animals in Wales

Liebana et al 2006 JCM 44:1630

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Escherichia coli producing CTX-M

ESBLs in food animals in Hong Kong

Pigs (n=300) 6 (2%) CTX-M-14, CTX-M-3,

CTX-M24

Cattle (n=96) 3 (3.1%) CTX-M-13,

Pigeons (n=33) 1 (3%) CTX-M-14

Chicken (n=243) 0

Geese (n=32) 0

Ducks (n=30) 0

Duan 2006 Microb Drug Resist 12:145

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Isolation of CTX-M ESBL positive Escherichia coli

from raw chicken meat sold in the West Midlands,

United Kingdom

British 1/62 CTX-M-1

Irish 0/3

Brazil 5/10 CTX-M-2

Brazil/Poland/France 3/4 CTX-M-2

Poland 0/4

Netherlands 2/2 CTX-M-2

E/F/DK/D 0/4

Unknown 6/40 CTX-M-2, 8, 14

Total 17/129 (13.2%)

Ensor, Warren, et al. 2007 Poster 1025, 17th ECCMID, Munich

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Community-acquired bacteraemia with

ESBL-carrying Enterobacteriaceae

• 80 episodes of non-nosocomial bacteraemia

• 11/80 ESBL: 3 community acquired; 8 health care associated

• ESBL: 8% E. coli; 25% Klebsiella spp., 20% Proteus mirabilis

• Admission from nursing home risk factor (OR 4.76, P=.001)

• 10.8% patients admission faecal carriage of ESBL organism

• 15.4% of colonised patients developed bacteraemia due to

CAZ-resistant organism during hospitalisation (OR 38.9;

P

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Distribution of ESBL-positive Escherichia coli in

long-term care facilities in Belfast area

A. Loughrey, P. Rooney, M. O'Leary, M. McCalmont, M. Warner, E. Karisik, P. Donaghy,

B. Smyth, N. Woodford, D. Livermore 2007 Poster 17th ECCMID Munich

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Conclusions

• CTX-M ESBL predominate in many parts of the

world

• Infections with ESBL-carrying Enterobacteriaceae

tend to originate increasingly in the community

• Carriage rate for ESBL-positive Enterobacteriaceae

may be substantial, but more data needed

• Colonisation of nursing home residents appears to

exceptionally high in some places

• ESBL-positive Enterobacteriaceae are found in food

animals

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Collaborators

Angharad P. Davies

Llinos Harris

Caron Jones

Naledi Bome

Irith Wiegand

Enno Stürenburg

Harald Seifert

Heinrich K. Geiss

Khalid El-Bouri

Ann M. Lewis

Nidhika Berry

EU ESF Fund

Wyeth