MRSA Prescreening and Eradication: New England Baptist Hospital Experience

David H. Kim, MD Director of Medical Education New England Baptist Hospital Boston, MA

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

55,000 54,000 53,000 52,000 51,000 50,000 49,000 48,000 47,000 46,000 45,000 48,213

2002

Total Inpatient Volume Massachusetts Market Orthopaedic Surgery

51,127

2003

52,625

2004

53,823

2005

54,171

2006

New England Baptist Hospital Market Growth ~ 11%

12%

10.82%

10%

8.20%

8%

6.22% 5.80%

6%

4.25%

4% 2% 0%

NEBH MGH BWH UMASS

2002 2003 2004 2005 2006

Baystate

Methicillin-resistant

Staphylococcus Aureus

S. Aureus

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

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

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 (1 st introduced antistaph PCN) – 1 st MRSA strain within 2yrs – 60% of clinical ICU’s are MRSA S. aureus strains isolated from

Linezolid

 Introduced in 2000 for MRSA –Resistant strain reported within 1 year [Tsiodras et al, Lancet 2001]

Daptomycin

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

Vancomycin Resistance

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

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]

MIC Creep

  ’d vancomycin failure rate in MRSA infections in setting of  ’d MICs – [Sakoulas et al, J Clin Microbiol 2005]

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]

SSI Costs

 Capitation – DRGs do not cover cost of treating nosocomial infection (considered “preventable”)

Risk of SSI Increased in Nasal Carriers

   Nasal carriage only independent risk factor for In S. aureus 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 S. aureus SSI in orthopaedic implant SSI, S.aureus

isolates from wound match nares 85% of time – Perl et al, N Engl J Med 2002

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]

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]

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]

Environmental Reservoirs

[Sexton et al, J Hosp Infect 2006]

Potential Airborne Transmission

[Sexton et al, J Hosp Infect 2006]

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]

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]

Long-term Care Facilities

 44% of environmental surfaces tested positive for MRSA [Asoh et al, Intern Med 2005]

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)

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

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%  (28 pts) with 85% power in S. aureus SSI (estimated reduction of 2.8% (57 pts) to 1.4% 4030 enrolled, 3551 completed study – 82.6% received at least 3 mupirocin doses [Perl et al, N Engl J Med 2002]

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

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

Incidence of MRSA Infections

[Harbarth et al, JAMA 2008]

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

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

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]

Pittsburgh Protocol

 Decolonization – Pts educated 1 wk preop – Mupirocin nasal ointment BID x 5 days – Chlorhexidine bath QD x 5 days

Pittsburgh Results

Pittsburgh Results

  No increase in infection from other pathogens Estimated economic gain of $231,741/yr

NEBH Experience: Background

   FY06 - 46 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

Anonymous Nasal Surveillance Cultures

February 2006--133 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

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

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

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.

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 aureus or MRSA S.

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

Results

 Study group (7/17/06 to 9/30/07) – 7019 patients screened  5122  1588  309 (73.0%) non-carriers (22.6%) S. aureus positive ( 4.4%) MRSA positive

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 6/5122 S. aureus (0.02%) (0.11%)  – 6/1897 (0.31%) in carriers   3/309 + MRSA 3/1588 + S. aureus (0.97%) (0.19%) SSI rate higher in carriers, highest in MRSA carriers

MRSA & S. Aureus SSI Rates

Time Period Inpatient surgeries Total SSI FY06 (no screening) 10/01/05-07/16/06 5293* 24 SSI Rate 0.46% FY07 (prescreening) 07/17/06-09/30/07 7019** 13 0.18% *historical controls **study group •61% Reduction in

S. aureus /MRSA SSI Rate

0.3

0.25

0.2

0.15

0.1

0.05

0

50% Reduction in MSSA SSI 60% Reduction in MRSA SSI MRSA SSI Rate MSSA SSI Rate

0.26% 0 .

18 % 0.13

% 0 .

06 % 07/17/06-09/30/07 07/17/06-09/30/07

Study Limitations

– Use of historical controls

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]

SSI Rate

 Spontaneous disappearance of deep infections (SSI surveillance effect?) – Implications for use of historical controls

[Kalmeijer et al, Clin Infect Dis 2002]

NEBH SSI Rates 2003-2008

GENERAL SSI

# Infections # Procedures Infection Rate

ORTHOPEDIC SSI

# Infections # Procedures Overall Infection Rate #Hip Infections Hip Prosthesis Rate Hip 0 Index #Knee Infections Knee Prosthesis Rate Knee 0 Index #Laminectomy Infec.

Laminectomy Rate #Spinal Fusions Infec.

Spinal Fusion Rate Other Ortho Infections Other Ortho Rate FY03 6 0.6

63 8837 0.7

14 1.0

21 1.6

6 0.7

5 0.8

FY04 1 1073 0.1

60 9669 0.6

5 0.3

14 1 9 0.9

15 2 17 FY05 3 920 0.4

49 9216 0.5

4 0.2

11 0.7

7 0.6

12 1.4

15 0.4

FY06 4 780 0.5

46 8986 0.5

7 0.4

0.0

7 0.4

0.2

7 0.8

12 1.1

13 0.4

2 692 0.3

39 9027 0.4

5 0.3

0.0

7 0.3

0.2

12 1.3

5 0.4

10 0.3

2 380 0.5

28 6809 0.4

4 0.3

0.0

10 0.6

0.4

4 0.6

2 0.2

6 0.3

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

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

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

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]

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

Concerns

NEBH Screening Results

    7/17/06 to 9/30/07 – 7019 patients screened   1588 (22.6%) S. aureus positive 309 ( 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

New England Baptist Hospital MRSA/MSSA Infection Rates

Time Period Inpatient surgeries Surgical Infections

FY06

10/01/05-07/16/06 5293 24 Infec. Rate 0.46%

FY07

07/17/06-09/30/07 7019 13 0.18%

FY08

10/01/07-06/30/08 4770 4 0.08%

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

Acknowledgements

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

, PhD

Thank You