Epidemiology of ESBL in hospitals and in the community

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<.001) 73% of community-acquired organisms carried CTX-M ESBLs Ben-Ami 2006 CID 42:925

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