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

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BETA LACTAM RING

PENICILLIN

BETA LACTAM RING

CEPHALOSPORIN

BETA LACTAMASES enzymes that inactivate the beta-lactam ring

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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.

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ESBL Evolution

Mid 1980sVariants of TEM and SHVBreakdown 3rd generation cephalosporinsMainly in hospital KlebsiellaSpread world wide

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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

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The rise of CTX-M in EuropeLivermore et al JAC (2007) 59 165-174

Increasing problem since 2000.Mainly in E coliNow over 50 types described1998 Poland CTX-M 3 & 152000 Spain CTX-M 92001 France CTX-M 152003 Italy CTX-M 1& 15

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Spread of CTX-M in the UK

2000-1 – First UK isolates (Klebsiella)2003 onwards – widespread across UKE coliEspecially CTX-M-15Five major clones A-EAlso diverse unrelated strains

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

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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

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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

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Maps of Europe and Shropshire,

UK.

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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.

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Start of the Shropshire outbreak

Multi-resistant E coli UTIs from May 2003

Mainly community patientsTwo E.coli strains

– Both resistant to quinolones, cephalexin and trimethoprim.

– Both sensitive to nitrofurantoin & carbapenems

– One strain (strain A) gentamicin resistant.

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Shrewsbury & Telford Tri Quin R ESBL E coli to Oct 04

0

2

4

6

8

10

12

14

16

18

20

8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11

2002 2003 2004

Gen S GenR

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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

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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.

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The evolution of the outbreak – Clinical and epidemiology 1.

In-patient cases initially in Telford Hospital Later spread to Shrewsbury HospitalNo obvious ward focus (21wards)90% Hospital contact in past 3 yearsBut in 10% cases no local acute hospital

contact.

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Time since last hospital discharge (readmissions): Patients<3 days post 2nd admission

01234567

days since last discharge

No

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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

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Response to the outbreak 2

March 2004 new hospital antibiotic guidelines introduced and strongly promoted

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Antibiotic Policy changes

Nitrofurantoin substituted for quinolones in UTIs

Imipenem substituted for quinolones in serious sepsis

Ertapenem introduced for ESBL sepsisGentamicin substituted for

cephalosporins in surgical prophylaxisReturn to amoxycillin in respiratory

tract infections

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Royal Shrewsbury Hospital - Antibiotic Reduction

0

0.02

0.04

0.06

0.08

0.1

0.12

Year 02-03 Quarter 1 03-04 Quarter 2 03-04 Quarter 3 03-04 Quarter 4 03- 04 Quarter 1 04-05 Quarter 2 04-05

IV Ciprofloxacin

Oral Ciprofloxacin

Norfloxacin

IV Cefuroxime

Cefalexin

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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

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Shropshire ESBL outbreakAug02-Dec04

0

5

10

15

20

25

30

2002

2003

2004

8 9 101112 1 2 3 4 5 6 7 8 9 101112 1 2 3 4 5 6 7 8 9 101112

Month

No.

Total genS

total genR

Total Both

Antibiotic policyIsolation ward

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“Do the sick no harm”

The ones that got away– If you do not look you will not find

Antibiotic disc problemsGentamicin assaysAsymptomatic carriage in the

communityYou are what you eat

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Quin,Tri,AmR Pod (Not S) LAB X

0

5

10

15

20

25

1 4 7 10 1 4 7 10 1 4 7 10 1 4 7 10 1 4 7

Quin,Tri,AmR Pod (Not S) Stoke

b

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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

Estimate of missed Lex S ESBL

0

50

100

150

200

250

300

Month

No

Cum estimate of notESBL

Cum not ESBL

Cum estimate of ESBL

Cum. definite ESBL

68 pats

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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

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No of gentamicin assays

0

50

100

150

200

250

300

9 10 11 12 1 2 3 4 5 6 7 8

2003 2004

Month

No. No of assays

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The iceberg effect

Opportunistic tests: No.tested Positive % Positive

Hospital patients 291 15 5.2%

Community patients

7/11 not hosp assoc.*

475 11 2.3%

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CTX-M isolated from chicken meat by country of origin

ECCMID 2007

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Where are we now ?

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0

5

10

15

20

25

30

5 8

10

12 2 4 6 8

10

12 2 4 6 8

10

12 2 4 6 8

10

12 2

2003Total 20

2004Total 147

2005Total 80

2006Total 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

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0

20

40

60

80

100

120

140

160

2002 2003 2004 2005 2006

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

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Conclusion

ESBL vs MRSA– Epidemic strains– Multiple antibiotic resistance– Laboratory tests

Detection Chromogenic agar

– Silent carriage Screening

– Hospital spread Isolation Hand hygiene

– Community reservoir

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And finally…

466 134

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