Molecular vs non-Molecular Testing for MRSA/MSSA: The Case for ...

Molecular vs non-Molecular
Testing for MRSA/MSSA:
The Case for Molecular
Lance R. Peterson, MD
Director of Microbiology and
Infectious Disease Research
Epidemiologist, NorthShore University
HealthSystem
Clinical Professor
University of Chicago, Chicago, IL USA

• Research Grants
Potential COI
– Bayer, Cepheid, NorthShore, GeneOhm, GSK, Johnson
and Johnson, Merck, MicroPhage, Nanogen,
Nanosphere, NIAID, Roche, 3M, Washington Square
Health Foundation, Wyeth (Pfizer), AHRQ
• Consultations (in conjunction with research
projects and new diagnostics)
– Cepheid, GeneOhm, GSK, MicroPhage, Nanogen,
Nanosphere, Roche, 3M, Wyeth (Pfizer)
• Industry support for this presentation
– None

Goals of the Presentation
• To present the case for molecular testing
when performing surveillance for MRSA and
MSSA
– MRSA control programs
– Pre-surgical testing to lower surgical site
infections
• Will not discuss clinical disease diagnostics
from direct specimens or detection of
staphylococci from blood culture bottles

US Infection Mortality 2005
FR DeLeo &
HF Chambers
JCI 119:2464, 2009

MRSA Risk Following Colonization
• 43,504 patients had surveillance for MRSA
• 7.4% of asymptomatic MRSA carriers developed
MRSA infection over 1 year
• 0.5% of MRSA nasal negative patients developed
infection over 1 year
• Over 10-fold higher risk of disease with MRSA
colonization
– Highest risk for MRSA infection is nasal carriage
(p

Do Colonized Patients Spread MRSA?
• Compared 58 patients with MRSA disease to
57 with nasal colonization to determine risk for
skin and environmental contamination
– Skin and environment contaminated 50 vs 47%
– Various skin sites 38-66% vs 30-63%
– Various environment sites 27-60% vs 21-63%
• Glove acquisition from skin 14-45% vs 16-38%
• “Strategies to limit transmission must address
colonized patients”
S Chang et al, CID 48: 1423-8, 2009

Risk for S. aureus Infection
• Systematic review (10 studies) to estimate of
the risk of infection following colonization with
MRSA compared with colonization by MSSA
• Random effects model was used to obtain
pooled odds ratio estimates
• Overall, colonization by MRSA was
associated with a 4-fold increase in the risk of
infection (odds ratio 4.08, 95% confidence
interval = 2.10-7.44) N Safdar et al. Am J Med 121:310-15, 2008

Critical Review of MRSA
Screening by Rapid Methods
• Review and meta-analysis of randomized, nonrandomized,
and observational studies
– Random-effects model was used
– Ten studies (nine interventional studies and one
unblinded, cluster-randomized, crossover trial) reviewed
• Between wards applying rapid screening tests and
those without screening, noted a significantly
decreased risk for MRSA bloodstream infections
• Overall, concluded that active screening for MRSA
is more important than the type of test used
E Tacconelli et al. Lancet Infect Dis 9: 546–54, 2009

Critical Review of MRSA
Screening by Rapid Methods:
Surveillance vs no Surveillance
E Tacconelli et al. Lancet Infect Dis 9: 546–54, 2009

Critical Review of MRSA
Screening by Rapid Methods:
Surveillance vs no Surveillance
E Tacconelli et al. Lancet Infect Dis 9: 546–54, 2009

Influence of Test Impact on Cost
Impact of a MRSA Program
• Excel-based decision-analytic model to
compare hospital costs and MRSA infection
rates for PCR or culture-based screening
• Simulated 370-bed hospital in the US
• Screening different populations gave savings
of $12,158–$76,624/month over no program
• Same-day PCR testing resulted in fewer
infections and the lowest total cost
N Olchanski et al. ICHE 32:250-7, 2011

How Can We Explain the
Variation in Results?

Performance of rtPCR and Culture
• 250 rtPCR positive and 250 rtPCR negative
samples tested by BD GeneOhm and two
Chromogenic media (direct and enriched)
• True Positive = culture positive or MRSA
history (n = 186)
CHROMagar
MRSA (Direct)
MRSASelect
(Direct)
CHROMagar
MRSA
(Enriched)
MRSASelect
(Enriched)
Sensitivity 80.6% 78.5% 86.6% 90.3%
Specificity 100% 97.4% 99.7% 91.6%
• Past performance showed rtPCR to be 98.2%
sensitive and 97.5% specific
SM Paule et al, AJCP 131:532-9, 2009
SM Paule et al, JCM 45:2993-8, 2007

Test Comparison
• Examined impact of turnaround time,
sensitivity, specificity and MRSA prevalence
on the characteristics of a surveillance
program
• Studied 37,179 consecutive MRSA-tested
admissions to NorthShore (one year)
Ari Robicsek, ICAAC/IDSA 2008
SM Paule et al, Am J Clin Pathol 131:532-9, 2009

% of isolation days missed
50
45
40
35
30
25
20
15
10
5
0
Missed Isolation Day Percentage: Method Comparison
Traditional or Chrom. Agar
Enrichment + Chrom. Agar
rtPCR
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84
Turnaround Time (hours)
Ari Robicsek, ICAAC/IDSA 2008

Predictors of Program Success
Author
Disease
reduced with
MRSA Mean Length of
Prevalence pre-emptive Hospital Stay
isolation
Test
Sensitivity
Time to
Result
Reporting
Length of
Intervention
Period
Estimated
MRSA Days
Captured
Program was
Successful
Harbarth et al 6.7% 3.7 to 4 days 84% ≥22.2 hours 5 to 17 months 63% No reduction in
disease
Harbarth et al 5.1% 6.4 days 84% ≥22 to23 hours 9 months 72% No reduction in
disease
Robicsek et al 6.3% 4.6 days 98% 15 hours 21 months 85% Reduction in
disease with
universal
surveillance
Jeyaratnam et al 6.7% 3.8 days 87.8% ≥22 hours 5 months 67% No reduction in
transmission or
disease
Hardy et al 6.3% 7.2 days 98% 22 hours 8 months 86% Reduction in
transmission
Hardy et al 5.2% 6.5 days ≤73% 42 hours 8 months 53% No reduction in
(direct culture)
transmission
Bowler et al 14.6% > 1 year 80% 48 hours 2 years 80% Reduction in
disease
L Peterson, JCM, 48:683-9, 2010

% of isolation days missed
50
45
40
35
30
25
20
15
10
5
0
Missed Isolation Day Percentage: Method Comparison
† = Failed Programs
* = Successful Program
†
Program † likely successful if capture
>80% of MRSA potential isolation days
*
*
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84
Turnaround Time (hours)
Traditional or Chrom Agar
Enrichment + Chrom Agar
rtPCR
Ari Robicsek, ICAAC/IDSA 2008; A Robicsek et al, An Int Med, 48:409-18, 2008; D Jeyaratnam et al, BMJ ,
336;927-30, 2008; S Harbarth et al, Crit Care 10:R25, 2006; Ari Robicsek, ICAAC/IDSA 2008; K Hardy et al,
Clin Microbiol Infect 10.1111/j.1469-0691.2009; WA Bowler et al. ICHE 31:269-75, 2010; WC Huskins et al.
NEJM 364:1407-18, 2011
†
*
†
†

Effectiveness of Various Strategies
Hospital-associated MRSA BSI incidence in December 2004:
Declined from a projected 4.6/1,000 to 1.5/1,000 patients
MRSA colonized patient LOS = 35 days
SS Huang et al, CID 43:971-8, 2006

Veterans Administration
Healthcare System (153 Hospitals)
• Reported 21-month results of all admission
screening for MRSA based on 1,312,840
admissions covering 8,318,675 patient days
• 45% reduction in MRSA disease in non-ICU
patients (P = 0.001) throughout the system
• 62% reduction in MRSA disease for ICU
patients (P < 0.001)
– 2 year baseline in ICU patients had no change in
disease
R Jain et al. NEJM 364:1419-30, 2011
• Testing primarily (92%) with rtPCR methods

Cluster Randomized Trial of ICU:
Demonstrated non-Utility of Culture
• Assessed VRE and MRSA surveillance plus
enhanced barrier precautions in the ICU
• 5,434 admissions to 10 intervention ICUs, and 3,705
to 8 control ICUs over 6 months
– Centralized, broth enriched culture used for testing
• Incidence of colonization or infection with MRSA or
VRE per 1000 patient-days at risk did not differ
significantly (P = 0.35)
• Mean (±SD) number of days from when surveillance
swab obtained until it was reported was 5.2±1.4
– 41% of patient days captured after reporting
WC Huskins et al. NEJM 364:1407-18, 2011

What About Surgical Site
Infections?

Changing Prevalence of
S. aureus in Surgery
• Percentage of S. aureus as a cause of
Surgical Site Infection in Coronary Artery
Bypass Grafting, Cholecystectomy,
Colectomy and Total Hip Arthroplasty rose
from 17% to 31% between 1992-2002
JA Jernigan, Maryland Patient Safety Center (NNIS), January 12, 2006

NorthShore Program for Detection of
Staphylococcus aureus Colonization:
Process Overview
• The patient is screened for S. aureus in the
nose 0-28 days prior to surgery
• If the test is positive, the physician will then
prescribe a 5-day course of mupirocin ointment
• The patient administers the nasal ointment
twice a day for the 5 days in the month prior to
surgery DM Hacek et al. Clin Orthop Relat Res 466:1349-55, 2008

Results of Preoperative Screening
for NorthShore Hip and Knee Surgery
Patients (n = 1,495)
• S. aureus SSI rate of decolonized S. aureus
carriers reduced 3.8-fold (p≤0.05)
• Overall S. aureus infection rate in screened
versus unscreened group was 0.8% versus
1.7% DM Hacek et al Clin Orthop Relat Res 466:1349-55, 2008

Prospective, Randomized Trial of
S. aureus decolonization
• Multicenter, prospective placebo controlled trial of
6,771 patients between 2005 and 2007
– Intervention was rtPCR screening with nasal
mupirocin/chlorhexidine bath for positive patients
• 808 positive patients had surgery
– 4 deep infections (0.9%) occurred in the treated group
– 16 infections (4.4%) occurred in the placebo group
» RR 0.21; 95% CI = 0.07-0.62
– LOS 1.8 days shorter in the treated group (p=0.04)
– Time to infection was shorter in the placebo group
(p=0.005) LGM Bode et al. NEJM 362: 9-17, 2010

What is the Role of PCR?

Performance of rtPCR and Culture
• Tested 5,838 paired nasal swabs to compare
Roche rtPCR MRSA assay and Chromogenic
MRSA agar (direct and broth enriched)
• True Positive = culture positive or MRSA
history (n = 397)
CHROMagar
MRSA
(Direct)
CHROMagar
MRSA
(Enriched)
rtPCR
Sensitivity 57.7% 67% 98.3% (96.3% to 99.2%)
Specificity 99.7% (98.6% to 99.1%)
P Patel et al, IDSA 2011

Summary
• MRSA surveillance in acute care settings at
modest prevalence likely requires a rapid
molecular test for success
• In long term care or where MRSA prevalence
is high, culture may be satisfactory
• For surgery patients, the higher sensitivity of
rtPCR likely makes this the preferred testing
approach