1. Infection Control Implications of ESBL producing organisms
David Paterson
University of Pittsburgh
Medical Center

2. Infection control and ESBLs
Classical infection control
Antibiotic modification
Digestive tract decontamination
ESBLs and nursing homes

3. Epidemiology of ESBL producers
Predominantly occur in hospitals and nursing homes
14 studies have used a case-control design to assess risk factors for ESBL producers
Plethora of conflicting results

4. Generalizations Group 1.
Seriously ill patients with prolonged duration of hospital stay, in whom invasive medical devices are present. Acquire ESBL producers days after admission.
Group 2
Elderly patients, frequently nursing home residents, with ESBL producers in urine

5. Molecular epidemiology
More than 50 studies have been performed using PFGE or other molecular epidemiologic techniques
In every study, at least one isolate has been obtained genotypically related to another
However, in some hospitals multiple clones circulate at any one time

6. Environmental contamination or transmission via hands?
Common environmental sources of ESBL producers appear to be uncommon
Ultrasound coupling gel (Gaillot 1998)
Bronchoscopes (Branger 1997)
Glass thermometers (used in axillary measurement of temperature) (Rogues 2000)
Cockroaches (Cotton 2000)

7. Environmental common source or patient contaminated environment?
Patients’ soap (Szabo 1999)
Sink basins (Hobson 1996)
Babies’ baths (Eisen 1995)

8. Documentation of hand carriage
Hand isolates have been identified which are genotypically identical to isolates causing infections in patients
Hand carriage disappears with directly observed hand hygiene
Prolonged hand carriage in a nurse with chronic dermatitis

9. GI carriage in health care workers?
Has been documented (Hobson 1996, French 1996), BUT
Is astonishingly rare and seldom protracted
EXCEPT, ESBL producing Salmonella in which prolonged GI carriage in health care workers has been documented (Mhand 1999, Hammami 1991)

10. GI colonization
Ratio of colonization to clinically significant infection is at least 2:1
In some outbreaks, 30-70% of all patients in ICUs have developed colonization
At least 80% of patients with infection can be documented to have prior GI colonization (Pena 1998, Lucet 1996)
We have documented persistence of GI carriage of at least one year

11. Detecting GI carriage
MacConkey agar with ceftazidime 4 mg/L (Pena 1997)
Nutrient agar with ceftazidime 2 mg/L, vancomycin 5 mg/L and amphotericin 1667 mg/L
Is a perirectal swab good enough?

12. Infection Control Scenarios
New occurrence of ESBL producers in hospital units where ESBL producers have not previously been endemic
Hospital units where ESBL producers have an established presence
Nursing homes

13. Initial outbreaks of infection
Consequences
Subsequent endemnicity
Change in empiric therapy (especially towards quinolones)
Emergence of resistance in Pseudomonas and Acinetobacter

14. Steps in preventing endemnicity
1. Perform rectal swabs to delineate the pool of patients who are colonized
2. Evaluate for a common environmental source of infection
3. Campaign to improve hand hygiene
4. Enforce contact isolation for patients found to be colonized or infected

15. Can gut carriage be interrupted?
Selective digestive tract decontamination
Erythromycin based therapies have not been effective (De Champs 1993, Decre 1999).
“Successful interventions”
Polymyxin, neomycin, nalidixic acid (Brun-Buisson 1989)
Colistin and tobramycin (Taylor 1991)
Norfloxacin (Paterson 2001)

16. Problems with quinolone prophylaxis
High frequency of quinolone resistant strains
Selection of quinolone resistant organisms (we did not document this)

17. Infection control in the endemic hospital
Is there any hope?
Lucet et al (CID 1999) – successful control of endemic ESBL producers
Reinforcing hand hygiene was not enough
Critical evaluation of nursing work practices which could lead to infection control breakdowns
Attention to visiting surgeons and radiographers
Formal notification of units to which patients were transferred

18. Antibiotic control
10 studies have analyzed relationship between third generation cephalosporin use and acquisition of an ESBL producing strain
5 found a significant association
3 were underpowered but p-values were between 0.05 and 0.10

19. Restriction of cephalosporins
Restriction of just third generation cephalosporins
Restriction of all cephalosporins (Rahal JAMA 1999)

20. Beta-lactam/beta-lactamase inhibitor combinations
Are they protective?
Case-control studies have shown lower use of clavulante based antibiotics in controls (Piroth 1998)
Replacement of 3GCs by piperacillin/tazobactam has been associated with reduction in ESBL producers

21. Patient to Patient
transmission
of genotypically
identical organisms
“In vivo” selection
by antibiotic use
Patient to Patient transmission facilitated
by antibiotic use

22. Nursing homes and ESBL producers
Up to 40% of nursing home residents have taken antibiotics in the last month (Smith 2000)
Infection control suboptimal in nursing homes
Urinary catheterization and decubitus ulcers are frequent
Point-prevalence in a Chicago nursing home – 46% of residents colonized with ESBL producers (Wiener 1999)

23. Risk factors Presence of a decubitus ulcer
Presence of a gastrostomy tube
Poor functional status
Prior receipt of ciprofloxacin
Prior receipt of trimethoprim-sulfamethoxazole
Wiener 1999

24. Contrasting experiences
Nursing homes are a reservoir of ESBLs for acute care hospitals (Wiener 1999)
Patients with hospital-acquired colonization or infection may return to their nursing home with ESBL carriage (Bird 1998)

25. Conclusions General principles to interrupt outbreaks
Identify colonized patients
Contact isolation
Reduction in all unnecessary antibiotic use, but especially cephalosporins
?? Gut decolonization

26. Unanswered questions
Effects of antibiotics on GI, skin and environmental contamination
Duration of GI carriage
“Virulence” factors