E. coli - Paul Ehrlich Gesellschaft

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

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

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

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

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

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

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

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

Long-term study of ESBL epidemiology
in Escherichia coli in Sevilla, Spain
Romero 2005 CMI 11:625

Dissemination of CTX-M type ESBL in
Enterobacteriaceae in People‘s Republic of China
Munday 2004 Int J Antimicrob Agents 23:175

Characteristics of CTX-M producing E. coli in
the Calgary Health Region 2000 to 2005
Pitout 2007 AAC 51:1281

Epidemiology of CTX-M-producing
Escherichia coli strains in the UK 2003/2004
Woodford 2004 JAC 54:735

Distribution of episodes of bacteraemia due to
ESBL-producing Escherichia coli
Rodriguez-Bano 2006 CID 43:1409

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.

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

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

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

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

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

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

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

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

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

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

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

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