PROFESSOR PETER M. HAWKEY

Transcription

1 Multi-drug resistant Escherichia coli PROFESSOR PETER M. HAWKEY School of Immunity and Infection College of Medical and Dental Sciences University of Birmingham Birmingham B15 2TT Health Protection Agency West Midlands Public Health Laboratory, Heart of England NHS Foundation Trust, B5 9SS

2 E coli bacteraemia to HPA for England,

3 CTX-M-1 Group CTX-M-2 Group CTX-M-8/25/26 Group CTX-M-9 Group

4 Proportions and country distributions of CTX-M ESBL genotypes a Israel c b Faecal isolates a Lebanon, b Israel, c Kuwait CTX-M-1 CTX-M-2 CTX-M-3 CTX-M-9 CTX-M-14 CTX-M-15 Others Hawkey & Jones 2009 JAC 64 Suppl 1 i3-i10

5 SMART study for E. coli / Klebsiella in IAI Hsueh et al. Int. J Antimicrob. Agents :408-14

6 BSAC UK bacteraemia susceptibility survey - E. coli % positive ESBL ESBL CTX-M (226) (230) (228) (228) (227) (223) (228) (427) (435) + number of strains

7 Prospective survey of West Midlands region April & May 2006 Population of 5.4 million with significant South Asian communities Laboratories in 13 major hospitals serving 90% of pop. Submitted all presumptive ESBL Enterobacteriaceae 370 isolates, 294 bla CTX-M positive 232 E. coli; 58 Klebsiella ll spp; 4 others Xu et al JAC :

8 Epidemiological and molecular characteristics of all 232 bla CTX-M positive E. coli strains belonging to clone O25b-ST131 and non-o25b-st131 Parameter O25b-ST131 n=154 No. of isolates (%) Non-O25b-ST131 n=78 Specimen Origin Hospital 88 (57.1) 40 (51.3) Community 66 (42.9) 38 (48.7) Specimen type Blood 14 (9.0) 5 (6.4) Urine 126 (81.8) 68 (87.2) Others 5 (3.2) 5 (6.4) Antimicrobial resistance ciprofloxacin 152 (98.7) 65 (83.3) trimethoprim 142 (92.2) 67 (85.9) gentamicin i 75 (48.7) 43 (55.1) bla CTX-M genotype bla CTX-M (99.4) 71 (91.0) bla CTX-M-9 1 (0.6) 1 (1.2) bla CTX-M-14 0 (0) 4 (5.1) bla CTX-M-2 0 (0) 2 (2.6) Presence of IS26 element 400 bp 41 (26.0) 0 (0) 873 bp 12 (7.8) 1 (1.3) Negative 102 (66.2) 77 (98.7)

9 PFGE of 225 bla CTX-M harbouring E. coli isolates from 13 hospitals in the West Midlands

10 Genotype and clonality of bla CTXM E.coli in West Midlands Stoke-on-Trent 1 ST131 (n = 7) 2 4 PFGE RE Dudley (n = 13) Shrewsbury (n = 14) Sandwell (n = 59) Stafford (n = 8) Redditch (n = 15) Walsall (n = 15) UHB b (n = 31) Burton-on-Trent (n = 8) HEFT a (n = 28) Nuneaton (n = 12) 8 Coventry (n = 20) Non- ST131 Non-FGE RE1 PFGE RE1 Hereford (n = 2) Non-PFGE RE1 2

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12 58/242 returning travellers with diarrhoea carried ESBL producing bacteria. 2/63 (3%) in Europe 50/138(36%) outside Europe Country Proportion (%) ESBL E. coli India 11/14 (79%) Egypt 19/38 (50%) Middle East 4/10 (40%) SE Asia (incl Australia) 5/13 (38%) Tham et al Scand J Infect Dis 42:275-80

13 Isolates were only identified to group genotype e.g., group 1, 2, 8, 9 & 25 90% +ve for bla CTX-M India only ygp1 Egypt & Thailand gp1 & 9 China only gp9 Tham et al Scand J Infect Dis 42:275-80

14 York ESBL study - Screening 1000 faeces samples Oct-Dec Enterobacteriaciae tested for ESBL production double disk diffusion screening 23 isolates screened for TEM, SHV & CTX-M Munday et al JAC 2004,54:

15 York ESBL producing isolates Species (number) CTX-M type SHV type TEM type Klebsiella spp. (1) CTX-M-9 SHV-36 - E. cloaceae (7) CTX-M-9 SHV-12 - E. coli (5) CTX-M-15 - TEM-2 E. coli (3) () CTX-M-14 - TEM-1 E. coli (1) CTX-M-9 TEM-1 Salmonella spp. (1) - SHV-12 - C. freundii (1) CTX-M-9 - -

16 Faecal carriage of CTX M ESBL in community faeces samples 727 samples cultured on chromid confirmed by double disc diffusion & API 20E 80 samples gave E. coli CTX M +ve All analysed by PFGE, 10 groups identified One example typed by MLST, All isolates screened by PCR for ST131. Wickramasinghe et al. LID submitted

17 Dice (Tol 1.0%-1.0%) (H>0.0% S>0.0%) [0.0%-100.0%] PFGE PFGE F075 F081 F012 ST131 85% Similarity Co de PFGE Clust er MLS T F040 F066 F079 F011 F029 Strain A F053 F060 F019 I I II II ST131 ST131 ST131 ST131 ST131 ST131 ST131 ST131 ST131 F019 F061 F070 F052 F021 F017 F074 F023 F037 III III III ST131 ST131 ST443 ST131 ST131 ST131 ST131 ST841 F037 F008 F046 F016 F024 F025 F002 F009 F010 IV IV V V ST2076 ST69 F106 F090 F100 F018 F078 F022 F080 F069 F104 VI VI VII VII ST69 F104 F015 F043 F063 F006 F028 F051 F004 F105 VII ST648 F020 F032 F039 F007 F076 F030 F001 F089.1 F102 VIII VIII VIII ST46 ST182 ST1312 F102 F003 F088 F005 F073 F071 F103 ST1312 ST940 ST1664

18 Proportions and country distributions of CTX-M ESBL genotypes a Israel c b Faecal isolates a Lebanon, b Israel, c Kuwait CTX-M-1 CTX-M-2 CTX-M-3 CTX-M-9 CTX-M-14 CTX-M-15 Others Hawkey & Jones 2009 JAC 64 Suppl 1 i3-i10

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20 Demography of Birmingham Total population: 997,087 Ethnicity % Population White 67.7 Asian 21.0 Black Chinese 3.2 Other 1.4 ONS 2007

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24 Appying OriginsInfo to give Cultural Ethnic Linguistic groupings 571 European 152 Middle Eastern/South Asian (MESA includes 4 African & 2 Chinese) 4 Unassigned

25 Distribution of CTX M genotypes according to global origin Global origin bla CTX-M bla CTX-M M9/14 bla CTX-M M15 ST131/Others Europe n= (8.1%) a 15 (2.5%) 31(5.4%) a 8/23 MESA n= (22.4%) a 7(45%) (4.5%) 27 (17.8%) a 6/21 a p < Wickramasinghe et al. LID submitted

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27 CTX-M producing E. coli isolated from chicken meat sole in U.K. by Country of origin Origin Total positive/ Total tested CTX-M enzyme present CTX-M-1 CTX-M-2 CTX-M-8 CTX-M-14 British 1/ Irish 0/ Brazil 5/ Brazil/Poland/France l 3/ Poland 0/ Netherlands 2/ Spain / France / Denmark / Germany 0/ Unknown 6/ TOTAL 17/ Warren et al JAC :504-8

28 Occurrence of ESBL genes in human infections and retail chicken meat produced in the Netherlands 262 raw meat samples cultured for ESBL in 2009 Chicken 80%, Pork 1.8%, Other meats 9.7% 4 hospitals covering same population p all Enterobacteriacae characterised for ESBL genes from : (i) 927 rectal swabs (4.9% ESBL +ve) (ii) Blood cultures 31 suspect cultures 23 PCR confirmed ESBL Overdevert et al submitted

29 Figure 1: Distribution of ESBL genotypes in chicken meat, rectal swabs and blood cultures chicken meat rectal swabs blood cultures Overdevest et al 2011 submitted

30 CARBAPENEM ANTIBIOTICS...

31 Fig. 1. Global distribution of KPC beta-lactamases. KPC-2 enzymes are denoted by red dots, all other KPC enzymes by blue dots. Walsh TR. Int. J. Antimicrob. Agents. 2010;S8-S14

32 Distribution of NDM-1-producing Enterobacteriaceae strains in Bangladesh, India, Pakistan, and the UK

33 NDM positive isolates from Sir Ganga Ram Hospital Delhi 9 patients (8/9 hospital inpatients) 2 E. coli. 7 Klebsiella 4 UTI, 3 cholecystitis, 1 intra-abdominal, abdominal, 1 VAP ALL isolates resistant to: ceftazidime, pip- tazobactam, meropenem, gentamicin, ciprofloxacin Number of isolates Sensitive to: 2/9 amikacin 1/9 nitrofurantoin 5/9 tigecycline 9/9 colistin Antimicrobial Research Group, Birmingham

34 Sir Ganga Ram Hospital NDM-1 isolates Isolate Location Isolate Location kb kb kb kb, 80kb kb kb kb kb kb kb, 175kb +Chrom 250kb 200kb 150kb 100kb 50kb ve ve

35 Carbapenemase-producing producing Enterobacteriaceae: ARMRL referrals from UK labs Year IMP VIM KPC OXA-48 NDM IMI

36 HPA Targeted molecular surveillance for carbapenemases in the Midlands 2010/11 10 hospitals submitted all 3GC resistant Enterobacteriacae Up to 50 Klebsiella spp & 50 E. coli and others All isolates screened with multiplex PCR for: IMP, VIM, KPC, NDM, OXA 48 & CTX M

37 624 isolates from hospitals (none 50 isolates) Carbapenemase Klebsiella spp E. coli & others Total NDM KPC OXA IMP 0 0 VIM CTX M gp CTX M gp

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48 Fig. 3. Representation of the global distribution of mobile metallo-b-lactamases. Walsh TR. Int. J. Antimicrob. Agents. 2010;S8-S14

49 Proportion of f3 rd generation cephalosporins resistant to E. coli isolates, EARSS data

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