1. 1 Extended spectrum B-lactamase producing E.coli in the community and in hospital Dr Graham Harvey Consultant Microbiologist Director of Infection Prevention & Control Shrewsbury & Telford Hospitals NHS Trust, Shropshire,UK

2. 2 BETA LACTAM RING PENICILLIN BETA LACTAM RING CEPHALOSPORIN BETA LACTAMASES enzymes that inactivate the beta-lactam ring

3. 3 Some beta-lactamases only inactivate a small number of antibiotics e.g. penicillin Others have extended spectrum to all the penicillins and cephalosporins e.g. cefuroxime, ceftriaxone (ESBLs) In addition may also carry resistance to other antibiotics e.g. ciprofloxacin.

4. 4 ESBL Evolution Mid 1980s Variants of TEM and SHV Breakdown 3 rd generation cephalosporins Mainly in hospital Klebsiella Spread world wide

5. 5 Control of a hospital outbreak of ESBL producing Klebsiella peumoniae Aberdeen, Scotland, 1992-4 ITU associated SHV-2 ESBL Increased use of third generation cephalosporins Only sensitive to amikacin & imipenem Environmental contamination (sinks) Improved plumbing ! Multi-disciplinary team approach

6. 6 The rise of CTX-M in Europe Livermore et al JAC (2007) 59 165-174 Increasing problem since 2000. Mainly in E coli Now over 50 types described 1998 Poland CTX-M 3 & 15 2000 Spain CTX-M 9 2001 France CTX-M 15 2003 Italy CTX-M 1& 15

7. 7 Spread of CTX-M in the UK 2000-1 – First UK isolates (Klebsiella) 2003 onwards – widespread across UK E coli Especially CTX-M-15 Five major clones A-E Also diverse unrelated strains

8. 8 www.hpa.org.uk/hpa publications/esbl_report_05/default.htm

9. 9 Health Protection Agency report September 2005 Recommendations –Laboratory detection of ESBL producers –Urine samples in Rx failures –Treatment guidelines –Better surveillance –Investigation of animal carriage

10. 10 Health Protection Agency report September 2005 Infection Control of CTX-M –Need for hospital and community guidelines –? Interventions needed –? Endemic in hospitals –Limited data as only recently emerged as a problem

11. 11 Maps of Europe and Shropshire, UK.

12. 12 Shropshire hospital setting 540,000 population. 2 main hospital sites 300 & 520 beds 30 Km apart – 7 intermediate care hospitals : 3 in Wales – 230 bed spinal injury & orthopaedic hospital – 12% single rooms – Minimal neutropenia / transplantation.

13. 13 Start of the Shropshire outbreak Multi-resistant E coli UTIs from May 2003 Mainly community patients Two E.coli strains –Both resistant to quinolones, cephalexin and trimethoprim. –Both sensitive to nitrofurantoin & carbapenems –One strain (strain A) gentamicin resistant.

14. 14

15. 15 E.S.B.L producing E coli in Shropshire 1 Jan 03 to 30 Sep 04 – 364 cases –68% female –mean age 74 years –49% community samples –Diabetes, dementia and malignancy

16. 16 Early Findings Gentamicin sensitive strain initially apparent as a community problem. – samples from GPs and few from psychiatric hospital. –Only 1 nursing home resident. –No apparent serious cases. Gentamicin resistant strain mainly in hospital patients.

17. 17 The evolution of the outbreak – Clinical and epidemiology 1. In-patient cases initially in Telford Hospital Later spread to Shrewsbury Hospital No obvious ward focus (21wards) 90% Hospital contact in past 3 years But in 10% cases no local acute hospital contact.

18. 18

19. 19 Response to the outbreak.1 Community/Hospital outbreak team (Aug 03) Letter to consultants/GPs Sept 03 Restrictive antibiotic reporting Increased use of carbapenems Cases isolated in side rooms

20. 20 Response to the outbreak 2 March 2004 new hospital antibiotic guidelines introduced and strongly promoted

21. 21 Antibiotic Policy changes Nitrofurantoin substituted for quinolones in UTIs Imipenem substituted for quinolones in serious sepsis Ertapenem introduced for ESBL sepsis Gentamicin substituted for cephalosporins in surgical prophylaxis Return to amoxycillin in respiratory tract infections

22. 22

23. 23 Response to the outbreak.3 Increased use of hand gel –Hand gel by each bedside Marking of patient’s electronic records Daily computer search for re-admissions Patient screening (stool & urine) “ESBL management unit” –Cohort ward –Opened May to June 04 –Closed July and August 04 –Re-opened September 04

24. 24 Shropshire ESBL outbreak Aug02-Dec04 Antibiotic policy Isolation ward

25. 25 “Do the sick no harm” The ones that got away –If you do not look you will not find Antibiotic disc problems Gentamicin assays Asymptomatic carriage in the community You are what you eat

26. 26

27. 27 Quinolone R Cephalexin S Urinary E coli Jan 2003 to March 2004 562 ESBL isolates in 370 patients 98 patients had CiproR TriR NitS “LexS” strains ESBL found in 27 of them 68 pats

28. 28 Laboratory testing issues Cefotaxime and ceftazidime or Cefpodoxime +/- clavulanate Manufacture (Oxoid) MHRA Batch to batch variation +/- 40% –10 ug could be 6-14 ug Mixing batches –Test like with like Storage esp clavulanate

29. 29

30. 30 The iceberg effect Opportunistic tests:No.testedPositive% Positive Hospital patients291155.2% Community patients 7/11 not hosp assoc.* 475112.3%

31. 31 CTX-M isolated from chicken meat by country of origin ECCMID 2007

32. 32 Where are we now ?

33. 33 2003 Total 20 2004 Total 147 2005 Total 80 2006 Total 53 2007 Shrewsbury and Telford NHS Trust New hospital cases of ESBL from May 2003 to March 2007 Ward opened May – June 04 Ward re-opened Sept 04 to Dec 05

34. 34 New Shropshire community cases of ESBL producing E coli from 2002 to 2006

35. 35 Conclusion ESBL vs MRSA –Epidemic strains –Multiple antibiotic resistance –Laboratory tests Detection Chromogenic agar –Silent carriage Screening –Hospital spread Isolation Hand hygiene –Community reservoir

36. 36 And finally… 466134 3572 36 780 26026 ESBL- 662 MRSA- 4002 C DIFF - 1104 Jan 2003 to Dec 2006 5274 patients with ESBL, MRSA and/or C DIFF ESBL 662 cases 9.3% C DIFF +ve 25.6% MRSA +ve