1. MRSA Prescreening and Eradication: New England Baptist Hospital Experience
David H. Kim, MD
Director of Medical Education
New England Baptist Hospital
Boston, MA 1

2. New England Baptist Hospital
150-bed adult medical/surgical hospital located in Mission Hill area of Boston
Orthopaedic subspecialty hospital & “Center of Excellence”
Acute inpatient discharges:
75% Orthopedic
8% General Surgery
17% Medical
Orthopaedic Surgery ~ 10,000/cases a year

3. Total Inpatient Volume Massachusetts Market Orthopaedic Surgery

4. New England Baptist Hospital Market Growth ~ 11%

5. Methicillin-resistant Staphylococcus Aureus5

6. S. Aureus Most important pathogen in SSI
Most SSI caused by strains carried by patient into hospital
Anterior nares main niche
Nasal carriage of S. aureus is risk factor for SSI [Kluytmans et al, Clin Microbiol Rev 1997] 6

7. MRSA vs. MSSA
Infection associated with higher mortality [Melzer et al, Clin Infect Dis 2003]
Survive in dry conditions & on inanimate surfaces up to 20 days [Clarke et al, Ir Med J 2001]
Prevalence increasing 7

8. History of MRSA Resistance to PCN within 1 yr
By 1950’s, 3/4 of S. aureus strains PCN-resistant
Today, 90-95% clinical strains PCN-resistant
1959—methicillin (1st antistaph PCN) introduced
1st MRSA strain within 2yrs
60% of clinical S. aureus strains isolated from ICU’s are MRSA 8

9. Linezolid Introduced in 2000 for MRSA
Resistant strain reported within 1 year
[Tsiodras et al, Lancet 2001] 9

10. Daptomycin Introduced in 2003 for MRSA
Resistant strain reported within 2 years
[Mangili et al, Clin Infect Dis 2005] 10

11. Vancomycin Resistance
Recognized after almost 40 yrs
1st glycopeptide-intermediate S. aureus (GISA) isolated in Japan in 1996 [Hiramatsu et al, J Antimicrob Chemother 1997]
High level resistance appeared in Detroit in 2002
vanA gene complex acquired from VRE [Centers for Disease Control and Prevention, MMWR Morb Mortal Wkly Rep 2002]
2nd strain in Philadelphia
3rd strain in New York 11

12. MIC Creep
Increases in vancomycin MIC in both MRSA & MSSA over time [Rhee et al, Clin Infect Dis 2005]
Largest study of >6000 S. aureus isolates over 5 yrs in California university hospital
Drift towards reduced susceptibility
ing percentage of isolates with MIC ≥ 1.0 μg/mL
19.9% in 2000
70.4% in 2004 [Wang et al, J Clin Microbiol 2006] 12

13. MIC Creep
’d vancomycin failure rate in MRSA infections in setting of ’d MICs
[Sakoulas et al, J Clin Microbiol 2005] 13

14. Surgical Site Infection (SSI)
Increased costs
Median hospital stay increased 2 wks
Rehospitalization rates doubled
Overall costs tripled
[Whitehouse et al, Infect Control Hosp Epidemiol 2002] 14

15. SSI Costs
Capitation
DRGs do not cover cost of treating nosocomial infection (considered “preventable”) 15

16. Risk of SSI Increased in Nasal Carriers
Nasal carriage only independent risk factor for S. aureus SSI in orthopaedic implant surgery
Kalmeijer et al, Infect Control Hosp Epidemiol 2000
SSI rate 2-9x higher in carriers
Kluytmans et al, Clin Microbiol Rev 1997
Perl et al, Ann Pharmacother 1998
Wenzel et al, J Hosp Infect 1995
In S. aureus SSI, S.aureus isolates from wound match nares 85% of time
Perl et al, N Engl J Med 2002 16

17. Risk Factors for S. Aureus SSI
Observational study of 357 cardiac surgery patients
27% nasal carriers
SSI rate 6.4%
S. aureus in 64%
8/16 infections in nasal carriers
Independent risk factors
Diabetes (RR 5.9)
Reoperation (RR 3.1)
S. aureus nasal carriage (RR 3.1)
[Munoz et al, J Hosp Infect 2008] 17

18. Risk of MRSA Nasal Carriage
Case-control study of 308 vascular surgery pts (nasal swabs)
11.4% MSSA carriers
4.2% MRSA carriers
2.9% on admission
1.3% acquired in hospital
Transfer from another dept or facility risk factors for MRSA carriage
MRSA infection rate
30.8% in MRSA carriers
0.68% in noncarriers
[Morange-Saussier et al, Ann Vasc Surg 2006] 18

19. Environmental Reservoirs
MRSA infected/colonized pts contaminate rooms, contribute to endemic MRSA
Prospective study of 25 MRSA pts
Sampling of isolation rooms
53.6% of surface samples positive
28% of air samples
40.6% of settle plates
Isolates identical or closely related in 70% of patients
[Sexton et al, J Hosp Infect 2006] 19

20. Environmental Reservoirs
[Sexton et al, J Hosp Infect 2006] 20

21. Potential Airborne Transmission
[Sexton et al, J Hosp Infect 2006] 21

22. Airborne Transmission
MRSA counts remain elevated for up to 15 minutes after bed making
Consider air ventilation & filtration
Keep doors closed
[Shiomori et al, J Hosp Infect 2002] 22

23. Inadequate Patient Space
18-month prospective study
Addition of fifth bed to four-bed bay
’d relative risk of MRSA colonization 315%
[Kibbler et al, J Hosp Infect 1998] 23

24. Long-term Care Facilities
44% of environmental surfaces tested positive for MRSA
[Asoh et al, Intern Med 2005] 24

25. Decolonization of Carriers
Intranasal mupirocin (Bactroban)
Eradicates nasal colonization in most patients
Reduces S. aureus infections
Herwaldt, J Hosp Infect 1998; Kluytmans et al, Infect Control Hosp Epidemiol 1996; Tacconelli et al, Clin Infect Dis 2003 (dialysis)
Cimochowski et al, Ann Thorac Surg 2001; Kluytmans et al, Infect Control Hosp Epidemiol 1996 (Cardiovasc)
Gernaat-van der Sluis et al, Acta Orthop Scand 1998 (ortho)
Perl et al, N Engl J Med 2002 (mixed) 25

26. Mupirocin and the Risk of S. Aureus (MARS) Study
University of Iowa
Prospective randomized double-blind placebo-controlled
4020 enrolled, 3864 analyzed
Elective cardiothoracic, general, oncologic, gyn, neuro surgery
Rate of S. aureus SSI (primary endpoint)
2.3% in mupirocin pts
2.4% in placebo pts
No reduction in rate of S. aureus SSI
Among nasal carriers, risk of nosocomial S. aureus infection decreased by half (7.7% to 4.0%)
[Perl et al, N Engl J Med 2002] 26

27. MARS Study Mupirocin nasal swab for up to 5 days
Chlorhexidine shower for cardiothoracic pts night before & morning of surgery
Power analysis
4046 pts to detect 50%  in S. aureus SSI (estimated reduction of 2.8% (57 pts) to 1.4% (28 pts) with 85% power
4030 enrolled, 3551 completed study
82.6% received at least 3 mupirocin doses
[Perl et al, N Engl J Med 2002] 27

28. MARS Study Infection Rates
Risk of S. aureus infection among nasal carriers cut in half
S. aureus SSI 4.5x higher in carriers receiving placebo
84.6% isolates from SSI pts identical between wound & nares
39 different strains among 77 patients
Mupirocin resistance in 6/1021 (0.6%) isolates over 4 yrs 28

29. Effect of Universal Screening: University of Geneva Hospital [Harbarth et al, JAMA 2008]
Prospective interventional cohort with crossover
21,754 pts (multiple surgical subspecialty wards)
Rapid screening + standard infection control measures vs. standard measures alone
MRSA Screening before or on admission by PCR
Standard infection control for MRSA carriers
Contact isolation
Gown, mask, gloves
Adjusted perioperative abx
Mupirocin & chlorhexidine x 5 days
Universal rapid MRSA admission screening did not reduce nosocomial MRSA infection 29

30. Incidence of MRSA Infections [Harbarth et al, JAMA 2008]30

31. Harbarth et al: Results
94% (10,193/10,844) screened
21,754 pts--70% power to detect reduction in MRSA infection rate from 0.9% to 0.6%
5.1% (515 pts) MRSA-positive
No difference in MRSA SSI rate
0.99% (76 pts) without screening
1.14% (93 pts) with screening
57% (53/93 pts) with nosocomial MRSA infection during screening period were MRSA-free on admission
31% of MRSA carriers identified after surgery
43% of MRSA carriers identified before surgery rec’d appropriate abx prophylaxis 31

32. Harbarth et al
None of MRSA carriers detected during outpatient preop visits developed MRSA infection
all received decolonization treatment & appropriate antibiotic prophylaxis
57% of infections hospital-acquired 32

33. Preoperative Decolonization
University of Pittsburgh
Prospective observational study
Total joint arthroplasty
1966 patients
636 screened (nasal)
26% positive for S. aureus (164/636)
23% MSSA (147/636)
3% MRSA (17/636)
1330 control (not screened)
[Rao et al, Clin Orthop Relat Res 2008] 33

34. Pittsburgh Protocol Decolonization Pts educated 1 wk preop
Mupirocin nasal ointment BID x 5 days
Chlorhexidine bath QD x 5 days 34

35. Pittsburgh Results 35

36. Pittsburgh Results No increase in infection from other pathogens
Estimated economic gain of $231,741/yr 36

37. NEBH Experience: Background
FY SSI in 8986 surgical pts (0.5%)
National rate for orthopedic SSI ~ 1.5%
57% SSI due to S. aureus
16 (35%) MSSA
10 (22%) MRSA
PFGE of isolates documented community acquired strains

38. Anonymous Nasal Surveillance Cultures
February anonymous nares cultures after patient anesthetized
Results:
38 – S. aureus (29%)
*5 - MRSA ( 4%)
all previously undiagnosed
*no precautions used in OR, PACU or nursing units
*Cefazolin used for antibiotic prophylaxis

39. Screening Proposals
February 2006 – prepared three screening proposals with costs
1) Traditional nasal cultures - 3 day results
$245,000.00
2) Purchase rapid PCR equipment
$337,338.00
3) Lease rapid PCR equipment
$259,990.00
March 2006 –Board approval of equipment purchase

40. Implementation – 8 Months
March – October 2006
Weekly meetings:
surgical services, infection control, micro, administration, & medical staff members
July 2006 – letter to surgeons
July 17, 2006 – initiated pilot on Spine Service
August 2006 – letter to medical staff
September 2006 – initiated universal program for all inpatient surgery

41. Policy & Procedure Formalization
Protocol developed for all departments & units affected
OR Scheduling
Patient Access
Prescreening Unit
Pre-surgical unit OR
PACU
Nursing Units
Microbiology Lab
Ancillary Departments: Housekeeping, Central Transport, Radiology, etc.

42. NEBH Program: Preoperative Outpatient Screening
Nasal swabs during prescreening
Microbiology Laboratory PCR detects presence of bacteria-specific DNA
Cepheid GeneXpert
Results within 24 hrs for S. aureus, 2 hrs for MRSA
Topical decolonization protocol for patients found to be carriers of S. aureus or MRSA 42

43. Topical Decolonization Protocol
Intranasal 2% mupirocin ointment (Bactroban) BID x 5 days
Shower with 2% chlorhexidine (Hibiclens) daily x 5 days
Patients called by PASU to initiate treatment protocol
Repeat call to document compliance
MRSA carriers re-screened prior to surgery
Contact precautions if 2nd MRSA screen positive
Vancomycin preop antibiotic prophylaxis for all patients with history of MRSA carrier status 43

44. Results Study group (7/17/06 to 9/30/07) 7019 patients screened
5122 (73.0%) non-carriers
1588 (22.6%) S. aureus positive
( 4.4%) MRSA positive 44

45. S. aureus & MRSA SSI Rate
13/7019 (0.18%) SSI cases in screened patients
7/5122 (0.14%) in noncarriers (0.14%)
1/5122 MRSA (0.02%)
6/5122 S. aureus (0.11%)
6/1897 (0.31%) in carriers
3/ MRSA (0.97%)
3/ S. aureus (0.19%)
SSI rate higher in carriers, highest in MRSA carriers 45

46. MRSA & S. Aureus SSI Rates
Time Period Inpatient surgeries Total SSI SSI Rate
FY06 (no screening)
10/01/05-07/16/ * %
FY07 (prescreening)
07/17/06-09/30/ ** %
*historical controls
**study group
61% Reduction in S. aureus/MRSA SSI Rate 46

47. 50% Reduction in MSSA SSI 60% Reduction in MRSA SSI
MRSA SSI Rate
MSSA SSI Rate
0.26%
0.18%
0.13%
0.06%
10/01/05-07/16/06
07/17/06-09/30/07
10/01/05-07/16/06
07/17/06-09/30/07 47

48. Study Limitations
Use of historical controls 48

49. Problem with Historical Controls
University of Amsterdam, The Netherlands
Prospective double-blind, placebo-controlled
614 pts
Elective ortho surgery with implants (hip, knee, spine)
Eradication rate 83.5% mupirocin, 27.8% placebo
No reduction in SSI rate (primary outcome)
Rate of endogenous S. aureus infection 5x lower
[Kalmeijer et al, Clin Infect Dis 2002] 49

50. SSI Rate
Spontaneous disappearance of deep infections (SSI surveillance effect?)
Implications for use of historical controls
[Kalmeijer et al, Clin Infect Dis 2002] 50

51. NEBH SSI Rates

52. Conclusions:
Program for comprehensive prescreening/treatment of S. aureus & MRSA prior to elective surgery is readily established & well-received
Program allows early identification of colonized patients, treatment, & adjustment of antibiotic prophylaxis, early isolation & contact precautions for MRSA
Associated with significant reduction in infections due to S. aureus & MRSA
MRSA colonized patients continue to have higher rate of SSI 52

53. NEBH Program Cost First year costs ~$400,000
~$100,000 for 2 full-time positions:
Microbiologist & PASU Medical Technician
~$60,000 PCR rapid test equipment
~Lab cost for PCR $40.00/test
(compared to routine culture ~ $20.00)
~ 6,000 inpatient surgeries = $240,000

54. Cost-effectiveness Analyses
Compared 3 strategies
Screen & treat
Treat all
Nothing
Assumptions
S. aureus carrier rate 23.1%
Mupirocin efficacy 51%, cost $48.36
Costs: septicemia $25,128, pneumonia $18,366, SSI $16,256
Both treatment strategies cost-saving
Treat all: prevents 1 infection/116 pts; 1 death/10,000 pts; save $88/pt
Screen & treat: prevents 1 infection/27 pts; 1 death/2500 pts; save $102/pt
[Young and Winston, Infect Control Hosp Epidemiol 2006] 54

55. Cost-effectiveness
Budget impact model of rapid testing & decolonization
7,181,484 elective surgeries in US (2003)
Rapid test cost $25/pt
sensitivity 52%
Specificity 85%
Decolonization cost $72.50/pt
56.5% effective
7.5% SSI rate
7.5% in carriers
1.5% in noncarriers
$231,538,400 cost saving, 364,919 fewer hospital days, 935 fewer in-hospital deaths
[Noskin et al, Infect Control Hosp Epidemiol 2008] 55

56. Intangible Benefits
NEBH S. aureus/MRSA prescreening & eradication program viewed very favorably as positive pro-active infection control measure by staff, patients, family members & media
Allows additional patient education on importance of hand hygiene, prevention of SSI, & infection control measures in home to reduce transmission of MRSA & S. aureus 56

57. Concerns 57

58. NEBH Screening Results
7/17/06 to 9/30/07
7019 patients screened
1588 (22.6%) S. aureus positive
( 4.4%) MRSA positive
through April 30, 2008
10,815 patients screened
2712 ( 25%) S. aureus positive
507 ( 5%) MRSA positive
Repeat nasal screens of MRSA carriers reveal 78% eradication rate
Prevalence of carriers increasing

59. New England Baptist Hospital MRSA/MSSA Infection Rates
Time Period Inpatient surgeries Surgical Infections Infec. Rate
FY06
10/01/05-07/16/ %
FY07
07/17/06-09/30/ %
FY08
10/01/07-06/30/ %

60. Conclusions Targeted active surveillance useful
In outbreaks
In high-risk populations, e.g. ICU’s
Efficacy of universal surveillance & eradication remains unproven
Depends on regional variations in MRSA/MSSA epidemiology
Depends on hospital surveillance data
Stanford vs. UCSF 60

61. Acknowledgements Maureen Spencer, RN Brian Kwon, MD
NEBH Board of Trustees
Joseph Dionisio, NEBH President and CEO
Ling Li, PhD
David Hunter, MD, PhD 61

62. Thank You 62