New technology for New technology for MRSA screening MRSA screening

Dr Richard CunninghamDr Richard Cunningham

Plymouth UKPlymouth UK

OutlineOutline

Should we screen for MRSA?Should we screen for MRSA? What methods are available?What methods are available? Why and how we introduced PCR Why and how we introduced PCR

testing in Plymouthtesting in Plymouth What effect it has had What effect it has had

Should we screen?Should we screen?

Is MRSA an important problem?Is MRSA an important problem? Does colonisation precede infection?Does colonisation precede infection? Is the test sensitive and specific?Is the test sensitive and specific? Is the yield enough to make it Is the yield enough to make it

worthwhile?worthwhile? Are effective interventions available?Are effective interventions available? Is the cost reasonable?Is the cost reasonable?

Effect of MRSA surveillance on Effect of MRSA surveillance on

CCUCCU (Huang et al, CID Oct 2006)(Huang et al, CID Oct 2006)

Harbarth Harbarth et alet al Critical Care Critical Care 20062006

Significant fall in Significant fall in transmission rate transmission rate on medical ICU on medical ICU after preemptive after preemptive isolation introducedisolation introduced

No change in No change in transmission rate transmission rate on surgical ICUon surgical ICU

PCR

Preemptive isolation

MRSA screening methodsMRSA screening methods

Liquid cultureLiquid culture ChromagarChromagar PCRPCR

In house assaysIn house assays IDI-MRSA/BD GeneohmIDI-MRSA/BD Geneohm GenoQuick MRSA assayGenoQuick MRSA assay

Other rapid methodsOther rapid methods Baclite (3M)Baclite (3M)

Other MRSA detection Other MRSA detection methodsmethods

ChromagarChromagar We use as confirmatory test and at We use as confirmatory test and at

weekendsweekends Less sensitive, highly specific, much Less sensitive, highly specific, much

cheapercheaper Takes 24-48 hoursTakes 24-48 hours

BacLiteBacLite Selective broth, immunomagnetic Selective broth, immunomagnetic

separation of MRSA, bioluminescent separation of MRSA, bioluminescent detectiondetection

93.4% sensitive, 96.7% specific, 93.4% sensitive, 96.7% specific, cheaper than PCRcheaper than PCR

Takes 5 hoursTakes 5 hours

Genoquick MRSA assayGenoquick MRSA assay

Holfelder et al Clin Micro Inf Dis 2006Holfelder et al Clin Micro Inf Dis 2006 242 patients, multiple body sites242 patients, multiple body sites Prevalence approx 5%, PPV 85%, NPV Prevalence approx 5%, PPV 85%, NPV

99%99%

Copyright © 2005 GeneOhm, Inc. – All rights reserved

9

IDI-MRSAIDI-MRSA™™ Assay Assay

Nasal Swab SpecimenPrep

Lysis - DNAExtraction

Reconstitution Real-time PCRAnalysis on theSmartCycler®Instrument

DefinitiveOn-screenResults

Results within 2 Hours

MRSA

MSSA

SCCmec orfX

orfX

Primers

DNA detection of the DNA detection of the SCCmecSCCmec--orfXorfX junction found junction found onlyonly in MRSA in MRSA provides definitive identification of MRSAprovides definitive identification of MRSA

Detects both HA-MRSA and CA-MRSA strainsDetects both HA-MRSA and CA-MRSA strains

Junction Regionfor Detection

StaphylococcalChromosomes

Remove supernatant

Add 50 µL Sample Buffer

Transfer entire cell suspension

Nasal Swab

Centrifuge5 min

Lysis Tube

Vortex inSample Buffer

1 min

95oC2 min4oC

Vortex5 min &

CentrifugeDNA

Cell Lysis and DNA Preparation

Extra spin

IDI-MRSA published test IDI-MRSA published test performanceperformance

Number Sensitivity % Specificity % Author

778 92.5 96.4 Manufacturers data

1657 MRSA

569 MSSA

98.7 95.4 Huletsky J Clin Micro 2004

287 96 96 Desjardins J Clin Micro 2006

75 89 97 DavidsonJ Hosp Inf 2006

1211 95 98.8 WrenJ Clin Micro 2006

DerrifordDerrifordHospital Hospital

1000 bed Teaching Hospital1000 bed Teaching Hospital19 adult critical care beds*19 adult critical care beds*Specialist unitsSpecialist units

Orthopaedic surgery*Orthopaedic surgery*Cardiac surgery*Cardiac surgery*NeurosurgeryNeurosurgeryThoracic surgeryThoracic surgeryPlastic surgeryPlastic surgeryRenal transplantRenal transplantHaematology/oncologyHaematology/oncology

Public perception 2005Public perception 2005

Quantifying our MRSA problemQuantifying our MRSA problem

Critical Care UnitCritical Care Unit 7%7%

Pre-operative assessmentPre-operative assessment Orthopaedic trauma Orthopaedic trauma 20% & 4%20% & 4% Orthopaedic elective Orthopaedic elective 2%2% Elective vascular surgery Elective vascular surgery 5.5%5.5% Elective general surgery Elective general surgery 4%4%

MRSA BacteraemiaMRSA Bacteraemia 98 cases in 03/0498 cases in 03/04

Solution - admission Solution - admission screening?screening?

Culture basedCulture based Elective vascular surgeryElective vascular surgery Elective orthopaedicsElective orthopaedics

PCR basedPCR based Critical care admissionsCritical care admissions Cardiac surgeryCardiac surgery Emergency orthopaedicsEmergency orthopaedics

ImplementationImplementation

Setting up laboratory Setting up laboratory aspects of PCR aspects of PCR testing is easy testing is easy

Convincing clinicians Convincing clinicians is straighforwardis straighforward

Persuading managers Persuading managers to fund it is difficult to fund it is difficult

Example business caseExample business case

3000 tests/yr3000 tests/yr Critical Care admissionsCritical Care admissions Elective cardiac surgeryElective cardiac surgery Emergency orthopaedic surgeryEmergency orthopaedic surgery

CostsCosts Capital Capital £30,000£30,000 ConsumablesConsumables £50,000£50,000 StaffingStaffing £25,000£25,000

Business caseBusiness case

Assume prevention of;Assume prevention of; 5 bacteremias5 bacteremias £37,500£37,500 3 mediastinitis3 mediastinitis £60,000£60,000 5 sternotomy infections5 sternotomy infections £50,000£50,000 4 orthopaedic implant infections4 orthopaedic implant infections £40,000£40,000 pre-op prophylaxispre-op prophylaxis £32,500£32,500

Predicted net savingsPredicted net savings £145,000/yr£145,000/yr

Antibiotic savingsAntibiotic savingsCardiac surgery prophylaxis (1000 cases, 3% prevalence)Cardiac surgery prophylaxis (1000 cases, 3% prevalence)

TeicoplaniTeicoplanin doses n doses (£34/dose)(£34/dose)

CefuroximCefuroxime doses e doses (£1/dose)(£1/dose)

Total costTotal cost SavingSaving

With MRSA With MRSA PCRPCR

3030 10001000 £1,962£1,962

£32,70£32,7088Without Without

MRSA PCRMRSA PCR10001000 10001000 £34,670£34,670

Critical Care MRSA PCR Critical Care MRSA PCR screeningscreening

693 CCU patients between 693 CCU patients between September 2005 and February September 2005 and February 20062006

Weekdays onlyWeekdays only Positive cases decolonisedPositive cases decolonised Patients not routinely isolatedPatients not routinely isolated Confirmed by cultureConfirmed by culture

0

5

10

15

20

25

April 0

5

May

05

June

05

July

05

Augus

t 05

Septe

mbe

r 05

Octob

er 0

5

Novem

ber 0

5

Decem

ber 0

5

Janu

ary

06

Nu

mb

er

of t

ran

smis

sio

ns/

10

00

pa

tien

t da

ys

0%

5%

10%

15%

20%

25%

MR

SA

po

sitiv

e o

n a

dm

issi

on

%

Culture screening PCR screening

ResultsResults

Results Results (transmissions per 1000 (transmissions per 1000 patient/days)patient/days)

Culture screening phase Culture screening phase 13.913.9 PCR screening phasePCR screening phase 4.9 4.9 (p<0.05)(p<0.05)

Relative risk reduction 65%Relative risk reduction 65%

Cunningham et al J Hosp Infect 2007

Critical Care Unit Critical Care Unit associated MRSA associated MRSA bacteraemiabacteraemia

02468

1012141618

2003

/4

2004

/5

2005

/6

2006

/7

MRSA status unknown

MRSA pos on admission

MRSA neg on admission

Screeningintroduced

Predictive value on CCU*Predictive value on CCU*

11stst Generation Generation testtest

22ndnd Generation Generation testtest

SensitivitSensitivityy

96.8%96.8% 97.2%97.2%

SpecificitSpecificityy

97.3%97.3% 99.4%99.4%

PPVPPV 70.4%70.4% 94.7%94.7%

NPVNPV 99.7%99.7% 99.7%99.7%*1026 patients, considered true positive if MRSA culture positive within 1 week of PCR result

Good negative predictive Good negative predictive value!value!

Orthopaedic surgeryOrthopaedic surgery Always a challenge!Always a challenge!

ProblemsProblems multiple teamsmultiple teams multiple wardsmultiple wards incomplete adherence to screening and incomplete adherence to screening and

antibiotic policiesantibiotic policies short timeframe between admission and short timeframe between admission and

surgerysurgery very low baseline infection rates make it very low baseline infection rates make it

difficult to assess impact of testingdifficult to assess impact of testing

SavingsSavingsPredictedPredictedreductionreduction

ObservedObserved

reductionreductionSavingSaving

BacteraemiBacteraemiaa

55 88 £60,000£60,000

SternotomySternotomy 55 1212 £120,00£120,0000

Antibiotic Antibiotic prophylaxisprophylaxis

£32,000£32,000

£212,00£212,0000

Better press this year!Better press this year!

MRSA cases fall at Devon hospital

Cases of the antibiotic-resistant superbug MRSA have fallen at the South West's biggest hospital. The figures are contained in a report to be discussed by Plymouth Hospitals Trust, which runs Derriford Hospital. The unconfirmed figures show a fall in both numbers and rates of cases. In the year to April Derriford had 88 cases - a fall of 10 from the previous year.

In the last year the hospital has been screening some patients before they are admitted to hospital for surgery. Those found to be carrying the bug are given eradication therapy to get rid of the bacteria before it becomes a problem for them or anyone else in the hospital. Derriford is also using a new state-of-the-art screening system, which reduces the detection of MRSA from five days to three hours, minimising the risk of infection.

Derriford Hospital is on course to hit its target for reducing bloodstream infections from MRSA, new figures show.Director of infection control Dr Peter Jenks has told councillors that Plymouth Hospitals Trust was two cases below its target for the financial year with just a couple of weeks to go.

Future plansFuture plans

From April 2007 expanded MRSA From April 2007 expanded MRSA screeningscreening PCRPCR

NeurosurgeryNeurosurgery Thoracic surgeryThoracic surgery Plastic surgeryPlastic surgery

CultureCulture Haematology & Oncology admissionsHaematology & Oncology admissions Acute medical admissions >60yrsAcute medical admissions >60yrs Acute surgical admissions >60yrsAcute surgical admissions >60yrs Elective surgical pre-assessmentElective surgical pre-assessment

Weekend serviceWeekend service

ConclusionConclusion

Is MRSA an important problem? - Is MRSA an important problem? - YesYes Does colonisation precede infection?- Does colonisation precede infection?- YesYes Is the test sensitive and specific?- Is the test sensitive and specific?- YesYes Does the yield make it worthwhile?- Does the yield make it worthwhile?- YesYes Are effective interventions available?- Are effective interventions available?- YesYes Is the cost reasonable?- Is the cost reasonable?- YesYes

Thank you for your Thank you for your attentionattention

Any questions?Any questions?