New technology for MRSA screening Dr Richard Cunningham Plymouth UK

Outline Should we screen for MRSA? Should we screen for MRSA? What methods are available? What methods are available? Why and how we introduced PCR testing in Plymouth Why and how we introduced PCR testing in Plymouth What effect it has had What effect it has had

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 worthwhile? Is the yield enough to make it worthwhile? Are effective interventions available? Are effective interventions available? Is the cost reasonable? Is the cost reasonable?

Effect of MRSA surveillance on CCU (Huang et al, CID Oct 2006)

Harbarth et al Critical Care 2006 Harbarth et al Critical Care 2006 Significant fall in transmission rate on medical ICU after preemptive isolation introduced Significant fall in transmission rate on medical ICU after preemptive isolation introduced No change in transmission rate on surgical ICU No change in transmission rate on surgical ICU PCR Preemptive isolation

MRSA screening methods Liquid culture Liquid culture Chromagar Chromagar PCR PCR In house assays In house assays IDI-MRSA/BD Geneohm IDI-MRSA/BD Geneohm GenoQuick MRSA assay GenoQuick MRSA assay Other rapid methods Other rapid methods Baclite (3M) Baclite (3M)

Other MRSA detection methods Chromagar Chromagar We use as confirmatory test and at weekends We use as confirmatory test and at weekends Less sensitive, highly specific, much cheaper Less sensitive, highly specific, much cheaper Takes hours Takes hours BacLite BacLite Selective broth, immunomagnetic separation of MRSA, bioluminescent detection Selective broth, immunomagnetic separation of MRSA, bioluminescent detection 93.4% sensitive, 96.7% specific, cheaper than PCR 93.4% sensitive, 96.7% specific, cheaper than PCR Takes 5 hours Takes 5 hours

Genoquick MRSA assay Holfelder et al Clin Micro Inf Dis 2006 Holfelder et al Clin Micro Inf Dis patients, multiple body sites 242 patients, multiple body sites Prevalence approx 5%, PPV 85%, NPV 99% Prevalence approx 5%, PPV 85%, NPV 99%

Copyright © 2005 GeneOhm, Inc. – All rights reserved 9 IDI-MRSA ™ Assay Nasal SwabSpecimen Prep Lysis - DNA Extraction ReconstitutionReal-time PCR Analysis on the SmartCycler® Instrument Definitive On-screen Results Results within 2 Hours

MRSA MSSA SCCmec orfX Primers DNA detection of the SCCmec-orfX junction found only in MRSA provides definitive identification of MRSA DNA detection of the SCCmec-orfX junction found only in MRSA provides definitive identification of MRSA Detects both HA-MRSA and CA-MRSA strains Detects both HA-MRSA and CA-MRSA strains Junction Region for Detection Staphylococcal Chromosomes

Remove supernatant Add 50 µL Sample Buffer Transfer entire cell suspension Nasal Swab Centrifuge 5 min Lysis Tube Vortex in Sample Buffer 1 min 95 o C 2 min 4oC4oC Vortex 5 min & Centrifuge DNA Cell Lysis and DNA Preparation Extra spin

IDI-MRSA published test performance NumberSensitivity %Specificity %Author Manufacturers data 1657 MRSA 569 MSSA Huletsky J Clin Micro Desjardins J Clin Micro Davidson J Hosp Inf Wren J Clin Micro 2006

Derriford Hospital 1000 bed Teaching Hospital 1000 bed Teaching Hospital 19 adult critical care beds* 19 adult critical care beds* Specialist units Specialist units Orthopaedic surgery* Orthopaedic surgery* Cardiac surgery* Cardiac surgery* Neurosurgery Neurosurgery Thoracic surgery Thoracic surgery Plastic surgery Plastic surgery Renal transplant Renal transplant Haematology/oncology Haematology/oncology

Public perception 2005

Quantifying our MRSA problem Critical Care Unit7% Critical Care Unit7% Pre-operative assessment Pre-operative assessment Orthopaedic trauma 20% & 4% Orthopaedic trauma 20% & 4% Orthopaedic elective 2% Orthopaedic elective 2% Elective vascular surgery 5.5% Elective vascular surgery 5.5% Elective general surgery 4% Elective general surgery 4% MRSA Bacteraemia98 cases in 03/04 MRSA Bacteraemia98 cases in 03/04

Solution - admission screening? Culture based Culture based Elective vascular surgery Elective vascular surgery Elective orthopaedics Elective orthopaedics PCR based PCR based Critical care admissions Critical care admissions Cardiac surgery Cardiac surgery Emergency orthopaedics Emergency orthopaedics

Implementation Setting up laboratory aspects of PCR testing is easy Setting up laboratory aspects of PCR testing is easy Convincing clinicians is straighforward Convincing clinicians is straighforward Persuading managers to fund it is difficult Persuading managers to fund it is difficult

Example business case 3000 tests/yr 3000 tests/yr Critical Care admissions Critical Care admissions Elective cardiac surgery Elective cardiac surgery Emergency orthopaedic surgery Emergency orthopaedic surgery Costs Costs Capital £30,000 Capital £30,000 Consumables£50,000 Consumables£50,000 Staffing£25,000 Staffing£25,000

Business case Assume prevention of; Assume prevention of; 5 bacteremias£37,500 5 bacteremias£37,500 3 mediastinitis£60,000 3 mediastinitis£60,000 5 sternotomy infections£50,000 5 sternotomy infections£50,000 4 orthopaedic implant infections£40,000 4 orthopaedic implant infections£40,000 pre-op prophylaxis£32,500 pre-op prophylaxis£32,500 Predicted net savings Predicted net savings £145,000/yr £145,000/yr

Antibiotic savings Cardiac surgery prophylaxis (1000 cases, 3% prevalence) Teicoplanin doses (£34/dose) Cefuroxime doses (£1/dose) Total cost Saving With MRSA PCR £1,962£32,708 Without MRSA PCR £34,670

Critical Care MRSA PCR screening 693 CCU patients between September 2005 and February CCU patients between September 2005 and February 2006 Weekdays only Weekdays only Positive cases decolonised Positive cases decolonised Patients not routinely isolated Patients not routinely isolated Confirmed by culture Confirmed by culture

Results

Results (transmissions per 1000 patient/days) Culture screening phase 13.9 Culture screening phase 13.9 PCR screening phase4.9 (p<0.05) PCR screening phase4.9 (p<0.05) Relative risk reduction 65% Relative risk reduction 65% Cunningham et al J Hosp Infect 2007

Critical Care Unit associated MRSA bacteraemia Screening introduced

Predictive value on CCU* 1 st Generation test 2 nd Generation test Sensitivity96.8%97.2% Specificity97.3%99.4% PPV70.4%94.7% NPV99.7%99.7% *1026 patients, considered true positive if MRSA culture positive within 1 week of PCR result

Good negative predictive value!

Orthopaedic surgery Always a challenge! Always a challenge! Problems Problems multiple teams multiple teams multiple wards multiple wards incomplete adherence to screening and antibiotic policies incomplete adherence to screening and antibiotic policies short timeframe between admission and surgery short timeframe between admission and surgery very low baseline infection rates make it difficult to assess impact of testing very low baseline infection rates make it difficult to assess impact of testing

Savings Predicted reduction ObservedreductionSaving Bacteraemia58£60,000 Sternotomy512£120,000 Antibiotic prophylaxis £32,000 £212,000

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 plans From April 2007 expanded MRSA screening From April 2007 expanded MRSA screening PCR PCR Neurosurgery Neurosurgery Thoracic surgery Thoracic surgery Plastic surgery Plastic surgery Culture Culture Haematology & Oncology admissions Haematology & Oncology admissions Acute medical admissions >60yrs Acute medical admissions >60yrs Acute surgical admissions >60yrs Acute surgical admissions >60yrs Elective surgical pre-assessment Elective surgical pre-assessment Weekend service Weekend service

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

Thank you for your attention Any questions?