11/12/2010

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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 CLINICCLEVELAND, OHIO Cleveland

Clinic ComplexDowntown

Cleveland

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

11/12/2010

2

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

Bad Hair Day

Feeling trapped

Sit back and relax!

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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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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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

0

2

4

6

8

10

12

14

16

18

1988 1991 1994 1997 2000 2003 2006 2009

# Publications

Modified from Perencevich EN and DM Treise. Infec Control

& Hosp Edidemiol. 2010; 31: S48-S50.

• 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

• Goes unnoticed and spreads

easily

Colonized

(asymptomatic)

Patients

Clinical

Infections

Sources:

Boyce et al., SHEA 1998, Abstract S74.

Zachary et al., ICHE 2001; 22:560-564.

Boyce et al., ICHE 1997;18:622.

MRSA: The Hidden Threat

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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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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

0

10

20

30

40

50

60

70

2005 2006 2007 2008

%m

rsa/s

a B

AC

TE

RE

MIA

Austria

France

Israel

Latvia

Romania

Belgium

Ireland

Italy

Poland

UK

Struelens MJ et al. Inf Cont Hosp Epidemiol 2010; 31: S42-44

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All hospital

admissions

High-risk

admissions• ER

• Hospital transfer

• Nursing home

MRSA Detection & Prevention

High-risk or

infected patients• ICU

• Surgical

• Burn unit

• NICU

MRSAFrequent

hospital visits• Dialysis

• HIV

• 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

ChromID MRSA from bioMerieux: green colonies

Remel Spectra MRSABioRad MRSA Select

BD CHROMagar MRSA

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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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MRSA Screening: comparison of GenOhm and

GeneXpert vs. Broth-enhanced culture

Sensitivity Specificity NPV PPV PPV

After

resolution

GenOhm 100% 98.5% 100% 82-

87%*

93-

94%*

Xpert 100% 98.2% 100% 67-

93%*

89-

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

FISH

5 h plus MRSA

confirmation

CHROMagar MRSA 24-48

PCR < 2.5 h

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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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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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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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Cardiac Surgery

SA Screen

Negative Positive

Mupirocin

Surgical Prophylaxis

Surgical Prophylaxis

PCN Allergic

Or

Aorta Case

Yes

Vancomycin

Aztreonam

No

Cefuroxime

MRSA Carrier?

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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PCR vs. Culture

What’s a Lab to Do?

Culture

• Relatively inexpensive

• No special training

• Isolate available for

epidemiological studies

• High throughput

possible

• Slow--not practical for:

– Pre-surgical

screening

– Pre-emptive

isolation

PCR

• May be more expensive

• May require special

training

• Still requires culture if

isolate is desired

• Some platforms have

limited throughput

• Rapid--useful for:

– Pre-surgical

screening

– 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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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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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!