1. MRSA: To isolate or not to isolate? Jean-François TIMSIT, MD PhD Medical ICU, University hospital Grenoble, France INSERM U 578 ESICM Barcelona – Sept 23th 2006

2. Why it is so important to control MRSA spread? Overmortality due to methicillin resistance?. Higher length of stay and cost - MRSA carriage increases the rate of S. aureus nosocomial infections - Indirect effects: broad spectrum antimicrobials, glycopeptide use (GISA,VRE)…

3. 2 main strategies to control MRSA spread Improve the compliance with standard precautions and hand hygiene for every patients Screen and Isolate MRSA carriers to prevent cross transmission

4. 4 points What are differences between standard precautions and barrier precautions in ICU patients ? Is barrier precautions effective ? –Yes: it is recommended and it works –Yes: many positive studies –Yes: Isolation +screening and flagging is associated with an improvement in compliance with hand hygiene Is barrier precautions effective ? –No: many methodological problems –No: Hand hygiene compliance per se is effective and could be sufficient Isolation decreases hand hygiene compliance Isolation is associated with serious adverse effects Isolation needs screening –No: It does not work in recent well designed studies Conclusion and possible attitudes?

5. What are differences between standard precautions and barrier precautions in ICU patients ?

6. Standard precautions vs contact isolation –Single-room, Isolation ward, cohorting (with or without designated staff) –Reinforcement of contact precautions targeted on MRSA carriers gloves, gown, mask With or without other measures: –screening, signalling and decontamination of MRSA carriers Definition of isolation

7. Is barrier precautions effective ? –Yes: it is extensively recommended by scientific societies and government autorities because –Yes: it works in many studies –Yes: Isolation (with screening and flagging) improve the compliance with hand hygiene

8. Recommendations Barrier precautions Single room, cohorting HIS/BSA CTIN SHEA (MRSA, 1998) (MRSA, ESB) (MRSA,ERV 2003) Gloves- Cantam. Mat. - Cantam. Mat. - Always Gown- All contacts - « large » contact- All contacts - Patient - Patient - Pt + Env. Hand - before+after - After-? Washing- SAS - SAS or HAS- HAS - Pt + Env. - Patient Mask- Nebuliz. - Nebuliz./proj. - Always

9. Epidemiology of MRSA Europe, bacteremia, 2002 (EARSS) (EARSS Annual report, 2003) 33% 44% 41% 42% 41% 35% < 1% 37% 34% EARSS : rates in France : - 34% in 2001 - 33% in 2002 - 30% in 2003 - 29% in 2004

10. MRSA French ICUs

11. Flagging and compliance to hand Hygiene Hand hygiene, ICU, all occasions (Girou et coll., SRLF 2000) all patientsMRB + –Before HAS52%51% –After HAS58%64% Hand hygiene after contact, ICU (Lucet et coll., CID 1999) No MRB MRB + –Jan 1993 46.2% 79.2% –June 1994 78.6% 93.5%

12. Flagging 85 entrance, 133 exit JC Lucet, Personnal communication

13. Is barrier precautions effective ? –No: many methodological problems –No: Hand hygiene per se is effective and could be sufficient Isolation decreases hand hygiene compliance Isolation is associated with serious adverse effects Isolation needs screening –No: It does not work in recent well designed studies

14. Efficacy of Isolation precautions Many positive studies…BUT A lot of confounding factors : - compliance with standard precautions +++ - MRSA screening - Icu turn-over and occupation rate - nurse/patient ratio and nurse workload - colonization pressure - use of antimicrobials Use of multiple isolation precautions

15. Regression to the mean and reporting biais: Is it an outbreak ? When interventions are made BECAUSE of unusually high MRSA levels or If the selection of the duration of periods are not randomized but choosen… There is a risk that subsequent reduction to be falsely attributed to the intervention

16. Regression to the mean and reporting biais: Is it an outbreak ? Control programs are frequently changed when MRSA levels increase Natural tendency to report successful interventions When such biases are operating, outcome data cannot be considered to provide a basis for making reliable conclusions about the effects of interventions. B e careful if the initial rate is very high and too short, or if the periods have not been randomly allocated. Appropriate description of patients and confounders

17. Is barrier precautions effective ? –No: many methodological problems –No: Hand hygiene per se is effective and could be sufficient Isolation decreases hand hygiene compliance Isolation is associated with serious adverse effects Isolation needs screening –No: It does not work in recent well designed studies

18. Hydro-alcoholic solutions Pittet et al, Lancet 2000; 356:1307 Hand hygiene improvement program

19. Compliance with hand hygiene and acquisition of MRSA Hand hygiene improvement program Pittet et al, Lancet 2000; 356:1307

20. Med. ICU, Chicago, 16 beds, 3 months MRSA screening per day (blind) Contact precautions if MRSA on clinical isolate Audit of hand hygiene and glove use Comparison to the routine clinical surveillance (1999-2002) Results 158 patients (2 refusals) 9 MRSA carriers on admission (5.6%) Daily endemic prevalence of MRSA: 10.5%  6.8% No MRSA acquisition!!! Nijssen et al., Clin Infect Dis 2005; 40:405

21. Surveillance, Isolation, and Spread of MRSA Nijssen et al - CID 2005:40 (1 February) 405 BUT : Low colonization pressure (10.5%) Short mean ICU stay (3.9 d.) Relatively low bed occupancy: 81% 1.9 contacts/h by nurse Nurse cohorting: 77% High compliance to standard precautions : Hand hygiene (53%), correct use of gloves (68%), both measures (78%)

22. Is barrier precautions effective ? –No: many methodological problems –No: Hand hygiene compliance per se is effective and could be sufficient Isolation decreases hand hygiene compliance Isolation is associated with serious adverse effects Isolation needs screening –No: It does not work in recent well designed studies

23. Gloves decreased hands colonization Pittet et al- Arch Intern Med.1999;159:821-826

24. 5 unit (3 ICUs) Observations of contacts : –Use of gloves –Adequacy of change –Adequacy of gloves removal –Hand hygiene after removal 23 h. of observation (69 x 20 min., 26 contacts/h.) Girou E, J Hosp Inf, 2004; 57:162

25. Hand hygiene after removing gloves: 69/129 (54%) 70 observations of contacts which required strict aseptic precautions in ICU: –Gloves not removed after previous care: 57/70 (81%) –Number of contact with the same gloves before aseptic care:2 (1 to 14)

26. Is barrier precautions effective ? –No: many methodological problems –No: Hand hygiene compliance per se is effective and could be sufficient Isolation decreases hand hygiene compliance Isolation is associated with serious adverse effects Isolation needs screening –No: It does not work in recent well designed studies

27. Decrease of care –« It is hard to go inside the room »... 2-fold decrease of visits 2-fold more iatrogenic events KB Kirkland et al - Lancet 1999; 354 : 1177–1178 Tranfer into hospital ward more difficult (single room) –Increase in the duration of stay Increase of anxiety and delirium in isolated patients Isolation could be dangerous..

28. Is barrier precautions effective ? –No: many methodological problems –No: Hand hygiene compliance per se is effective and could be sufficient Isolation decreases hand hygiene compliance Isolation is associated with serious adverse effects Isolation needs screening –No: It does not work in recent well designed studies

29. Systematic screening vs clinical samplings Clinical=8 Screening= 31 Medical ICU, 18 beds, 1200 admissions per year

30. MRSA screening is needed Lucet et al – Arch Intern Med 2003; 27:181-8 - Prévalence : 6.9% (95%CI : 5.9 – 8.0%) - Identification of MRSA by screening alone : 88(54.3%) 14 ICUs (6 months, 2475 admissions)

31. Systematic vs targeted screening Cost-Benefit Analysis Lucet et al – Arch Intern Med 2003; 27:181-8

32. Rapid screening and pre-emptive isolation Geneva: Nov 2003-Aout 2005/ 2 ICUs Comparaison –screening/rapid q-PCR screening –Pre-emptive vs/non pre-emptive contact isolation qPCR:1227 pre-emptive isolation days saved Decrease in the rate of MRSA infection (surg ICU only) Harbarth S et al – Crit Care 2006; 10:R25

33. Is barrier precautions effective ? –No: many methodological problems –No: Hand hygiene compliance per se is effective and could be sufficient Isolation decreases hand hygiene compliance Isolation is associated with serious adverse effects Isolation needs screening –No: It does not work in recent well designed studies

34. Single room in the ICU ? Methods 2 centres (A:18+4, B:10 beds) (single room or bays) MRSA screening on admission, weekly and at discharge 3 periods For all the patients “reinforced”standard precautions: –Apron every nurse shift –Gloves only for contact with body fluid and washing Cepeda JA et al, Lancet 2005; 365:295 3 months Single-room or cohort isolated 3 months Single-room or cohort isolated 6 months Non-move phase

35. 1676 admissions 1346 hospital A, 330 hospital B 866 patients included 599 hospital A, 267 hospital B P 1 and 3 (MOVE) 443 admissions (309 Hp A - 134 Hp B) 92 MRSA on admission (20.8%) (52 Hp A - 40 Hp B) 54 MRSA acquisitions 12% 38 hôpital A, 16 hôpital B P 2 (NON-MOVE) 423 admissions (290 Hp A - 133 HP B) 76 MRSA on admission (18%) (33 Hp A - 43 Hp B) 42 MRSA acquisitions 10% 29 hôpital A, 13 hôpital B 810 excluded (DS < 48 h) 1hospital A 63 hospital B

36. Hôpital B Hôpital A MRSA acquisition MRSA imported Cepeda JA et al, Lancet 2005 N patients in the ICUColonization pressure P1P2P3 Hos A Hos B

37. BUT Median duration of stay : 6 to 7 days Imported cases : 19.4% Colonization pressure: 50 to 90% Delay between admission and move > 3 days Compliance : – apron 99% (change between patients?) but – hand hygiene: 22%, despite a high nurse/Pt ratio closed to 1

38. When –MRSA is High –Colonization pressure is tremendously high –Compliance with hand hygiene is low –No additional barriers beyound hand hygiene –Nurse/patient ratio is 1:1 … The risk of transmission is not significantly reduced by moving patients into private rooms or isolating them with like patients

39. Possible attitudes Discard the barrier precautions appears risky: –Environment contamination in the room occurred in 70% of infected of colonized MRSA patients (Boyce JM, Infect Control Hosp Epidemiol 1997; 35: 139467) –Effect on other MRB ( VRE, ESBL)

40. In ICU Screening-contact precautions is effective Compliance of standard precaution is key (HAS++) : –weak (< 40%) : any other measures are useless –Excellent (>70% ?, or even more ?) : Standard precautions might be sufficient –Use of gloves ? –Systematic audit on hand hygiene and glove use It is probable that contact precautions improve the overall “hygiene” of the ICU –Don’t change a winning team –ICUs is one of the driving force in hospital hygiene: If we stopped contact precaution, we will be followed by the hospital ward… Possible attitudes

41. MRSA: possible strategies Association of Screening and contact precautions is the standard in the ICUs Going back to standard precaution alone??? – Imported cases / colonization pressure very low – Team trained and experienced in hygiene precautions, with the use of HAS – Systematic and repeated audits of compliance with hand hygiene and gloves use – MRSA epidemiologic surveillance (screening on admission + clinical isolates)