Extended spectrum B-lactamase producing E.coli in the community and in hospital

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

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

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

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. The rise of CTX-M in EuropeLivermore 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. 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. www.hpa.org.uk/hpa publications/esbl_report_05/default.htm

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. 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. Maps of Europe and Shropshire, UK.

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. 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.

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

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. 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.

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

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

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. Shropshire ESBL outbreakAug02-Dec04 Antibiotic policy Isolation ward

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

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. 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

30. The iceberg effect

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

32. Where are we now ?

33. 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 2007 2003 Total 20 2004 Total 147 2005 Total 80 2006 Total 53

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

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. MRSA- 4002 ESBL- 662 3572 466 134 36 26 260 780 C DIFF - 1104 And finally… 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