1. Multi-resistant Gram-negatives bacteria: Move over MRSA - new kids on the superbug block
8th Annual Infection Prevention Conference
23rd June 2011, Harrogate
Kevin Kerr
Harrogate and District NHS Foundation Trust/ Hull York Medical School 1

2. Extended-spectrum beta-lactamase
What is an ESBL?
Extended-spectrum beta-lactamase
Enzyme capable of conferring resistance to:
Penicillins
1st, 2nd, 3rd generation cephalosporins
Aztreonam
(But not cephamycins or carbapenems)
Inhibited by clavulanic acid in vitro
Plasmid mediated 2

4. The ESBL family TEM SHV CTX-M PER VEB TLA BES FEC GES SFO CME BEL PME
RAHN
CSP
Klebsiella species
esp K. pneumoniae
Escherichia coli
Proteus spp.
Morganella morganii
Providencia spp.
Pseudomonas aeruginosa
Acinetobacter spp.
Enterobacter spp.
Citrobacter spp.
Salmonella spp.
Capnocytophaga ochrachea
Vibrio spp
Aeromonas spp
Rahnella 4

5. 5

7. Public and media perception of ESBLs
Google News Archives
Hits
MRSA
14 300
C. difficile
2 300
ESBL
658 7

8. MRSA HCAI TOP TRUMPS ESBL Transferable Resistance WINS
Difficult to detect in the lab
No national guidance on which patients to screen
No national mandatory surveillance of bacteraemias
No national guidance on Infection Control
No national guidance on treatment
Few treatment options
Eradication of carriage not possible 8 8

10. Risk factors for ESBL Studies vary Study populations Case Selection
Control groups
Sample size
Prior hospital stay especially on ITU/SCBU
Mechanical ventilation
Poor APACHE score
Poor nutritional status
Enteral/parenteral feed
CVC
Urinary catheter
Recent surgery
Decubitus ulcers
Haemodialysis
Previous antibiotic use
Total use
3rd generation cephalosporins
Quinolones
Nursing home residence 10

11. Treatment options for ESBL11

13. Mortality associated with ESBL infection
Country
Patient category
Mortality rate ESBL (%)
Mortality rate non-ESBL (%)
P value
Korea1
Haematological malignancy
44.8
14.2
<0.001
Korea2
Community
12.1
16.0
n.s.
Spain3
Oncology 41 21
0.003
Israel4 30 11
Canada5
Mixed hospital 13 7
Italy6
29.7
6.1
1 Kang et al Ann Hematol In press
2 Lee et al Diag Micro Infect Dis 2011;70:150-3
3 Gudiol et al J Antimicrob Chemother;66:657-66
4 Marchain et al Antimicrob Ag Chemother;54:
5 Otner-Agostini et al Can J Inf Dis Med Micro 2009;3:43-44
6 Tumbarello et al Antimicrob Ag Chemother 2010;54:

14. Thank heavens for carbapenems...
KPC
Plasmid-mediated resistance to carbapenems
K. pneumoniae
Spreading rapidly

15. Gaibani et al Euro Surveill 2011;16(8):pii=19800

16. Carbonne et al Euro Surveill 2010;15:(48):pii=19734

19. NDM-1 as at December 2010

23. J Antimicrob Chemother 2010;65:1604-1607
Antibiotic
MIC (mg/L)
Interpretation
Ampicillin
>32 R
Co-amoxiclav
>256/2
Piperacillin/tazobactam
>256/4
Cefoxitin
>256
Cefotaxime
Ceftazidime
Cefepime
128
Aztreonam
.256
Imipenem 32
Meropenem 16
Ertapenem 64
Ciprofloxacin
Gentamicin
Amikacin
Trimethoprim
Tetracycline
Tigecycline 2
Colistin
J Antimicrob Chemother 2010;65:

24. Carbapenemase-producers: other therapeutic options
Combinations of traditional antibiotics
Colisitin + rifampicin
Colistin + vancomycin
Sulfactams
New tetracyclines
E101
Fluorocyclines
GSK
New aminoglycosides (ACHN-490)
New beta-lactamase inhibitors (eg nxl-104)

25. Infection control – one size does not necessarily fit all
2004
2005
2006
MRSA
0.55
0.57
0.45*
ESBL
0.04
0.06
0.08*
*P =
Bertrand et al Eur J Clin Microbiol Inf Dis 2008;27:

26. Pitout et al Clin Infect Dis 2004;38:1736-1741
Esbl
Pitout et al Clin Infect Dis 2004;38: 26

28. 28 Saudi paper 2007 13% of individuals 0f 56
Kader et al Infect Control Hosp Epidem 2007;28: 28

30. ...and even more spanners

31. Tackling multi-resistant Gram-negatives...why bother?31 31

32. Controlling MR-GNB: what can be done?
Control antibiotic use especially if the problem is polyclonal
Isolation of patients and contact precautions especially if clonal spread suspected 32

33. Antimicrobial stewardship
Tängdén et al J Antimicrob Chemother 2011;66:1161-7 33

34. Tängdén et al J Antimicrob Chemother 2011;66:1161-7

35. Tängdén et al J Antimicrob Chemother 2011;66:1161-7

36. Antimicrobial stewardship
Does my patient really need an antibiotic?
Prescribe in accordance with your local antibiotic policy
If prescribing empirically, “de-escalate” broad spectrum therapy when the microbiology results are known
Colonisation does not equal infection 36

37. Controlling MR-GNB: what can be done?
Control antibiotic use if polyclonal
Infection control measures if clonal spread suspected 37

38. Infection control measures
Eliminate environmental reservoirs
Isolation of infected/colonised patients
Increased hand hygiene
Gut decolonisation? 38

39. Infection control measures
Eliminate environmental reservoirs
Screening and isolation of infected/colonised patients
Increased hand hygiene 39

40. MR-GNB control at Harrogate District Hospital (HDH)40

41. 303 patients admitted with acute diarrhoea
96 (31.7%) were carriers of MR-GNB
Cf MDR in 618/5764 (10.7%) of clinically relevant isolates
14 (15%) were aged ≤25 yrs; 10 (10.4%) never been hospitalised
Vidal-Navarro J Antimicrob Chemother 2010;65: 41

42. Screening for MR-GNB: unanswered questions
Who to screen?
How to screen?
When to screen?
How often to screen?
Who pays? 42

43. Screening for MR-GNB: unanswered questions
What do you do with the results?

44. Isolation of patients as a control measure
Only 6.8% clearance. Some remained pos over the three year period
Schwaber et al Clin Infect Dis 2011;52: 44

45. Infection control measures
Eliminate environmental reservoirs
Screening and isolation of infected/colonised patients
Increased hand hygiene 45

46. Conclusions 1 MR-GNB are widespread in hospital and community settings
Carbapenems are the drugs of last resort for serious ESBL-associated infection…
…but resistance to carbapenems has emerged and is spreading rapidly
Some MR-GNB infections are becoming untreatable 46

47. Conclusions 2
There is no systematic surveillance for ESBLs and other MR-GNBs in many countries
There is no agreement on how to screen and which patients to screen for MR-GNB carriage in hospitals
Eradication of faecal MR-GNB carriage does not appear possible...
...so “traditional” infection control measures are important 47

48. Conclusions 3
ESBLs have entered the food chain (and are also found in food-borne pathogens such E. coli O157 and Salmonella spp)
We are doing too little to control MR-GNBs at a national and international level
More resources for control and treatment are needed but other HCAI may distort priorities 48