Presented by Dr. Hall at the 40th Annual Symposium "Diagnostic and Clinical Challenges of 20th Century Microbes", held on Nov 18, 2010 in Philadelphia.

1. 11/12/2010
Comparison and Cost Effectiveness of
MRSA Screens: Molecular vs. non-molecular
methods
Gerri S. Hall, Ph.D.
Eastern PA Branch, ASM
November 18, 2010
hallg@ccf.org
CLEVELAND CLINIC
Downtown CLEVELAND, OHIO Cleveland
Cleveland Clinic Complex
CCF: ~ 1000 hospital beds
12 family health centers
Medical School
Medical Technology School
Reference Laboratory
OBJECTIVES
• TO DISCUSS IMPACT OF HOSPITAL
ACQUIRED INFECTIONS (HAI) ON THE
CLINICAL MICROBIOLOGY
LABORATORY
• TO DESCRIBE THE METHODS FOR
MRSA SCREENING
• TO PRESENT OUTCOMES DATA ON
MRSA SCREENING PROGRAMS
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2. 11/12/2010
Conflict of Interest
• Speaker for Becton-Dickinson and bioMerieux
• Consultant: Opgen, Intelligent MDx
• Most recently involved in research with:
– bioMerieux
– Pocared
– Advandx
– MicroPhage
– Prodesse
• Committees/Boards
– CLIAC
– CAP Microbiology Resource Committee
– ASCP Teleconference Committee; RIS Committee
– ASMBL: ASM Branch Lectureship Program; CPEP
Sit back and relax!
Bad Hair Day
Feeling trapped
Snooze and chewz
What are HAI’s
• Site & procedure Specific
– Bloodstream Infections (BSI)
– Urinary Tract Infections (UTI)
– Ventilator-Associated Pneumonia (VAP)
– Surgical Site Infections (SSI)
• Mediastinitis following cardiac surgery
• Vascular Surgery
• Orthopedic Surgery
• Neurologic Surgery
• Pathogen Specific
– C. difficile
– MRSA
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3. 11/12/2010
Reasons for HAI Prevention
• Better patient care
– HAI‘s affect 1 in 20 patients in US hospitals per year
– ~100,000 deaths have been attributed to HAI‘s
• Reduced costs to healthcare
– ~ $33 billion dollars in excess medical cost
• 28 States now mandate public reporting of HAI‘s
• Goals of 2009 action plan of Federal government to
prevent HAI‘s
– Reimbursement will decrease or not exist for HAI ‗s
– Present data on HAI‘s do not include non-hospital settings
• 26,000 non-hospital healthcare settings
• The right thing to do
Zero Tolerance to HAI’s
• Consumers (patients) want this
• CMS wants this
• Insurance companies want this
• Healthcare workers want this
• Is it really possible?
– Speaker’s opinion: Probably not realistic to
have ―Zero‖ HAI‘s
• but we can still work to reduce HAI‘s where and
when that is possible
Magnitude of the problem:
Methicillin Resistant S. aureus
• ~293,000 hospitalizations in U.S. annually are diagnosed with S.
aureus infections
– ~0.8% all hospital discharges
– MRSA = ~60% of these SA episodes
~0.3% all hospital discharges
MRSA in community (CA-MRSA): unknown incidence but rising
• MRSA HAI attributable costs were reported as $35,367 (APIC study
1990-2000; Stone PW et al. AJIC 2002; 30: 145-52)
• ISPOR report in 2005 estimated annual cost to treat MRSA in US
hospitals was $3.2 – $4.2 billion
– Pfizer, Inc. Infect Cont today 2005;
– http://www.infectioncontroltoday.com/hotnews/55h168584264313.
html.
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4. 11/12/2010
Impact of MRSA
• Nosocomial Infections
– Associated with prolonged hospital stays, prolonged ICU
stays and longer antibiotic associated LOS
– Associated with greater costs
• Abramson calculated excess attributable cost of $27,083 for MRSA
bacteremia vs. $9,661 for MSSA bacteremia
• Engemann showed 1.9 fold increase in hospital charges among pts.
with MRSA surgical site infections
• Leads to higher rates of vancomycin usage thus selecting for
vancomycin-resistant pathogens
Engemann JJ, et. al. Adverse clinical and economic outcomes attributable to methicillin resistance among
patients with Staphylococcus aureus surgical site infection. Clin. Infect. Dis. 2003; 36:592-98.
Abramson MA, et. al. Nosocomial methicillin-resistant and methicillin-susceptible Staphylococcus aureus
primary bacteremia: at what costs? Infect. Control Hosp. Epidemiol 1999; 20:408-11.
Chaix C, et. al. Control of endemic methicillin-resistant Staphylococcus aureus. JAMA 1999; 282:1745-51.
―Superbug‖ publications in
medical literature by year
18
16
14
12
10 # Publications
8
6
4
2
0
1988 1991 1994 1997 2000 2003 2006 2009
Modified from Perencevich EN and DM Treise. Infec Control
& Hosp Edidemiol. 2010; 31: S48-S50.
MRSA: The Hidden Threat
Clinical
Infections
• MRSA colonization is
asymptomatic
• Reservoirs are mainly skin
and nares
• Spread occurs from a colonized
patient to another, usually via a
healthcare worker’s hand
Colonized
• Goes unnoticed and spreads
(asymptomatic)
easily
Patients
Sources:
Boyce et al., SHEA 1998, Abstract S74.
Zachary et al., ICHE 2001; 22:560-564.
Boyce et al., ICHE 1997;18:622.
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5. 11/12/2010
MRSA Screening - Is It
Inevitable?
―Search and Destroy‖
European Strategy
for MRSA Control
―Search and Destroy‖
• Long-standing, intensive, coordinated campaigns in
Denmark, the Netherlands, and some other European
countries relies on targeted screening of high-risk
patients.
– When multiple cases of MRSA are noted, entire units can be
closed for comprehensive screening and cleaning
– Health care workers are screened for carriage and if colonized,
not allowed to work til they are successfully decolonized
• Pan et al. ICHE 2005;26:127-33
• Verhoef et al. 1999; EJCMID 18: 461-6
• Vandenbroucke-Grauls et al. 1996; ICHE 17: 512-3
• Kluytmans-Vandenbergy et al. 2005; Infection 33: 309-13.
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6. 11/12/2010
Is U.S. Different from Europe in
MRSA Incidence and Screening?
• Mean % of cases of SA caused by MRSA
in hospitalized patients = 20%
– Wide variation in Europe from 1% in some
Nordic countries to > 50% in So. European
countries
• European CDC recently estimated MRSA causes
> 171,000 HAI leading to 5400 deaths and > 1
million extra hospital days
What are the MRSA programs in
Europe 1999-2007?
• A combination of the following was identified in Belgium, UK
and France:
• Structural
– Antimicrobial stewardship
• ―prudent use of antibiotics‖ committees developed
– Dept. of Health Improvement team visits
– Increased funding for ICP‘s and antibiotic managers
• Regulatory
– Mandatory reporting of MRSA BSI rate
– Mandatory participation in MRSA surveillance
• General Infection Control
– Hand hygiene and campaigns for it
– Care ―bundles‖
• MRSA Control
– MRSA control guidelines
– MRSA BSI reduction target goals of ~ 50^
Decreasing trend in % of SA bacteremia
caused by MRSA in 10 European Countries
70
Austria
%mrsa/sa BACTEREMIA
60 France
50 Israel
40 Latvia
Romania
30
Belgium
20 Ireland
10 Italy
Poland
0
UK
2005 2006 2007 2008
Struelens MJ et al. Inf Cont Hosp Epidemiol 2010; 31: S42-44
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7. 11/12/2010
MRSA Detection & Prevention
High-risk or
infected patients All hospital
• ICU admissions
• Surgical
• Burn unit
• NICU
MRSA High-risk
Frequent admissions
hospital visits • ER
• Dialysis • Hospital transfer
• HIV • Nursing home
• Long-term care
• Screening programs can be effective for
various groups of patients
Laboratory Screening for MRSA
• Conventional Culture
– Culture on blood agar; incubate overnight; pick colonies
consistent with S. aureus; do a catalase and coagulase for
confirmation; set up MIC and read results next day
– Time range for report: 2 days; most work; least specific; ?? Quite sensitive,
although not necessarily the most sensitive method.
– Culture on ―selective media‖ ex: Mannitol salt agar (MSA)
• S. aureus colonies will be yellow next day; prove ID and do an MIC as
above
– Time range for report: 2 days; more selective, but less sensitive
• Culture on Selective MRSA Chromagar
– Culture onto agar that detects MRSA by growth and a color change
in the media; > 4 commercial manufacturers
– Requires 24-48 hrs for detection; up to 85% in first 24 hrs can be
detected for most of the Chromagar
– Chromagar comparison: Yang HY et al. Ann Cin Lab Sci 2010; 40: 252-6
Remel Spectra MRSA
BioRad MRSA Select
ChromID MRSA from
BD CHROMagar MRSA bioMerieux: green colonies
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8. 11/12/2010
Laboratory Screening for MRSA:
Molecular Methods
• Molecular Methods for detection
– Detection of MRSA directly in the clinical samples (nasal
swab)
• BD GenOhm MRSA Assay (Becton Dickinson)
– Specimen processing manual; automated read—
about 1 ½ to 2 hrs; with 2 Smart Cyclers, can run ~25
samples in this time
• Xpert MRSA Assay (Cepheid)
– Minimal processing; automated read; single tests
can be run; batching not required; each run is about
75 min., so total time for a sample would be about 1
½ hr.
• Roche ASR: on Light Cycler
– Detection of MSSA and MRSA in nasal swabs by both BD
GenOhm and Cepheid GenXpert: can also be used for
positive blood cultures as well.
The SmartCycler
• Random Access to
each I-CORE module
• Amplification and
detection in single
step
• Closed-tubes
minimize
contamination
Rapid, Easy, Test Set Up
(per Cepheid)
5.
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9. 11/12/2010
MRSA Screening: comparison of GenOhm and
GeneXpert vs. Broth-enhanced culture
Sensitivity Specificity PPV
NPV PPV
After
resolution
GenOhm 100% 98.5% 100% 82- 93-
87%* 94%*
Xpert 100% 98.2% 100% 67- 89-
93%* 92%*
• 425 patients: 414 nasal and 389 groin swabs (378 patients with
both)
• * range represents nasal and inguinal alone or the two combined
– Hombach M et al. JCM 2010; 48: 3882-7
MRSA Screening: comparison of GenOhm and
GeneXpert vs. Broth-enhanced culture
• Authors conclusion:
– Both assays performed well
– Combining nasal and groin increases rate of detection
– Increased inhibition with taking samples from other
sites than nares and groin
– NPV excellent, thus back-up cultures unnecessary
– Back-up cultures for + may be needed due to low
PPV
• However PCR may ne new gold standard
– Xpert MRSA had better TAT than BD GenOHM
Time to Detection of MRSA
Summary of Various Screening Methods
Method Time Required (hours)
SAB > 48
MSA ~72
SBA + oxacillin > 48
Enrichment broth/PNA 5 h plus MRSA
FISH confirmation
CHROMagar MRSA 24-48
PCR < 2.5 h
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10. 11/12/2010
Costs of Molecular vs Non-
Molecular testing
• Everyone‘s instrument and reagent costs vary as
do the salaries and benefits of laboratory
personnel
– Non-molecular
• 0.20 for a BAP vs. 0.50 for a MSA vs. $4- $5 for a MRSA
selective Chromagar
• + cost, if needed of the disk or other AST assay if done
– Molecular (wide variance if home-brew or purchased)
• $30,000 - $75,000 for equipment
• $25-30 or more per test for reagents
» Diekema DJ and MB Edmond CID 2007; 44: 1101-7.
What will be done with the MRSA
Screening Results?
• Test for MRSA only or MSSA and MRSA
• If Positive for whatever of the above:
– Mupirocin will be employed in the nares for
• Prevention of infection in patient
• Prevention of transmission of one patient to another
and/or
– Patients will be isolated to prevent transmission
and/or
– Data is being collected :
• To determine prevalence
• To report MRSA in your hospital
• To know results in an individual patient for future care
• WHAT IS DONE WITH THE DATA WILL HAVE TO GO INTO THE
DECISION OF WHAT TEST TO USE FOR SCREENING !
Outcomes data I found and
would like to Share
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11. 11/12/2010
Evanston Hospital Experience
• Developed a strategic plan to implement total hospital
admission screening for MRSA using the BD GeneOhm
assay and have been doing this starting in August 2005
– 40,000 annual admissions (850 bed complex)
– 100 samples/day, 7 days per week
– MRSA + patients are decolonized and placed into isolation:
• 5 days mupirocin
• Chlorhexidine baths day 1, 3, and 5
– Have been able to demonstrate:
• a reduction in serious MRSA infections
• Reduction in MRSA respiratory infections
• Very little mupirocin resistance
• Cost savings above cost of the program: $300,000 to $1 m.
Rapid MRSA screening and pre-emptive contact
isolation for control of MRSA in critical care unit
• Multiplex PCR used in 2 adult ICU‘s in Switzerland 2003-
2005
– Prevalence of previously unknown MRSA carriage was high at
ICU admission
– Only a small number of pts had their first MRSA from a clinical
culture
– Rapid PCR permitted significant reduction in TAT: from 4 days to
1 day, as compared to culture
– No effect on MRSA rates in SICU, but many pre-emptive
isolation days could have been saved
– Substantial decrease in MRSA infection in MICU after linking
rapid PCR result to pre-emptive isolation and cohorting of MRSA
pts.
• Harbarth S et al. Critical care 2006; 10: R25
Rapid MRSA Screening in General
Hospital Wards: UK study
• Cluster randomized crossover trial that
compared PCR with culture
– rapid MRSA screening for MRSA on admission did
not reduce MRSA rates on general wards where pre-
emptive isolation was in place
– An impact was found on isolation and barrier nursing,
but formal cost effectiveness analysis was not done
• Did not feel increased costs would be justified
• Jeyaratnam D et al. Br Med J 2008; 336: 927-30
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12. 11/12/2010
Screening Plus Intranasal Mupirocin and
Chlorhexidine Bathing IN ICU
• All patients in Medical-coronary ICU were
screened for MRSA and if colonized:
– Intranasal mupirocin was administered
– Daily chlorhexidine bathing
• 52% decrease in colonization and ―infection‖
• Mupirocin resistance remained low (4.4%)
• Chlorhexidine resistance did not appear
• Ridenour G et al. Infect Cont Hosp Epidemiol 2007; 28:
1155-61.
7 year experience with MRSA
Surveillance (Culture) in NICU
• 8/2000-8/2007: 7997 infants admitted
– 102 (1.3%) positive (infection or colonized)
• 2000: 1.79 cases/1000 pt days – 0.15/1000 pt days in 2005
to 1.26/ 1000 pt days in 2007
• 15% had invasive infection: no difference between infected
and colonized identified
• 14 different antibiograms for MRSA identified
• 20002004: mainly HA-MRSA
• 2006-2007: mostly Ca-MRSA
– 19,090 screening cultures
• $1,500,000 not billed to insurers ($71 for ID and $91 for AST)
» Gregory et al. Pediatrics 2009; 123: e790-6.
Use of Statistics and Models for
Outcomes of MRSA Screening
• Cardiac Surgery
– Routine pre-op MRSA screening provides substantial
economic value to 3rd party payers and hospitals over
a range of MRSA colonization prevalence rate,
success levels and surveillance costs
• Lee BY et al. Am J Managed Care 2010; 16: e163-73.
• Orthopedic Surgery
– Pre-op screening and decolonization was strongly
cost-effective from 3rd party payer even with MRSA
prevalence as low as 1%, or decolonization success
was as low as 25% and decolonization costs were as
high as $300. From hospital standpoint, MRSA
screening and decolonization was economically
dominant strategy for all scenarios explored
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13. 11/12/2010
Cardiac Surgery
SA Screen Surgical Prophylaxis
PCN Allergic
Negative Positive Or
Aorta Case
Yes No
Mupirocin
Cefuroxime
Vancomycin
Aztreonam
MRSA Carrier?
Surgical Prophylaxis If Yes Add
Vancomycin
Is MRSA Screening necessary?
• Australian study to decrease burden of endemic MRSA in ICU (8.5 yr
retrospective study)-
– 2000 admissions/year; no active screening or contact isolation done
– Regression modeling to evaluate trends in SA prevalence density, antibiotic
consumption, infection control consumables, alcohol-based hand run solution
(ABHRS)
• Results
– MRSA decreased by 83%
– Rates of MRSA BSI decreased 89%
• No changes in MSSA bacteremia
– Hospital MRSA prevalence decreased 17%
– Antibiotic usage decreased 26% in ICU coinciding with decrease in MRSA
• Decrease in MRSA associated with ABHRS—but introduced late in study after MRSA
declines seen
• Conclusion: General QI measures were associated with decrease in
endemic MRSA in high-risk setting without resource intense active
surveillance and isolation practices.
– Ananda-Rajah MR et al. Intensive Care med 2010; 36: 1890-8.
Knowledge Gaps related to New
Interventions to Prevent MRSA
• Better understanding of colonization and
transmission including inter-facility
transmission across the spectrum of
health care
• Control of antibiotic use
• Effective vaccine targets
– From: Frieden, TG (CDC Director).
• Infec Control Hosp Epidemiol 2010; 31: S1-S3.
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14. 11/12/2010
PCR vs. Culture
What’s a Lab to Do?
Culture PCR
• Relatively inexpensive • May be more expensive
• No special training • May require special
• Isolate available for training
epidemiological studies • Still requires culture if
• High throughput isolate is desired
possible • Some platforms have
• Slow--not practical for: limited throughput
– Pre-surgical • Rapid--useful for:
screening – Pre-surgical
– Pre-emptive screening
isolation – Pre-emptive isolation
What does a Hospital DO about active
surveillance for MDRO/HAIs?
• Prepare the Laboratory
– Start with one organism and get that going
• Focus on all aspects of the Intervention
• Measure Meaningful Outcomes
• Discuss Impact on Infection Control
Program
• Diekema and Edmond
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15. 11/12/2010
Who Pays for Surveillance
Cultures and Programs?
• Patients as part of a ― standard of care‖
• The Microbiology Laboratory
• Infection Control departments
• Hospital Administration
• Other
• Sometimes it will just have to be done!
Hand Hygiene: an essential piece
of any Prevention programs
• MRSA rates have fallen off over the past rates in many
US hospitals:
– Nasal Screening
– Rapid PCR methods
– Isolation
– Chlorhexidine baths
– NasalMupirocin
– Hand Hygiene efforts
– All of the above
• Canadian study: systematic hand hygiene of patients
and relatives was found to be an inexpensive and highly
effective preventive measure against nosocomial
transmission.
Thanks
• Dr. Alan Evangelista for asking me to speak
• Pennsylvania ASM Branch for inviting and
supporting me today
• You, the audience
• Medical technologists who do such a great
job at laboratory surveillance and detection
• Infection Control Practitioners who do such a
great job to help prevent and reduce
infections
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16. 11/12/2010
Websites
• www.apic.org/Content/NavigationMenu/Ed
ucation/Online
learning/webinars/070110_robicsek.pdf:
data in powerpoint from Evanston Hospital
assumptions
• www.aacc.org/AACC/publications/cln/2007
/august/cover1_0807.htm (Clin Lab News)
Wishing you Successful
outcomes!
Wash your Hands and Have a
Great Day!
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