Point of Care Testing – Point of Care Testing – Clostridium difficleClostridium difficle

Amita PatelAmita Patel

Guy’s and St Thomas’ NHS Foundation Guy’s and St Thomas’ NHS Foundation TrustTrust

Project AimProject Aim

““Measuring the Clinical Value and Measuring the Clinical Value and impact of impact of C. difficleC. difficle Point of Care Point of Care testing (POCT) in ICU and Care of testing (POCT) in ICU and Care of

Elderly wards”Elderly wards”(Project duration 18 months)(Project duration 18 months)

Project StakeholdersProject Stakeholders

Cepheid GeneXpert SystemCepheid GeneXpert System

FDA approval for C. difficile 2009First truly molecular POCT for CDI

Key End PointsKey End Points

►Carriage and likelihood of InfectionCarriage and likelihood of Infection

►Predictability of virulencePredictability of virulence

►POCT – as a platform does it work?POCT – as a platform does it work?

►Turnaround times and its impact on Turnaround times and its impact on PatientPatient

Key End points – Infection Key End points – Infection

►Measure the prevalence of carriage of Measure the prevalence of carriage of (toxigenic and non-toxigenic (toxigenic and non-toxigenic C. difficileC. difficile))

►Measure likelihood of developing Measure likelihood of developing infection in those that are carriers and, infection in those that are carriers and,

►Establish if source of infection is Establish if source of infection is endogenous or exogenousendogenous or exogenous

End points – Virulence End points – Virulence PerspectivePerspective

►Reliability of presumptive 027 Reliability of presumptive 027 identification by comparison to PCR identification by comparison to PCR ribotypingribotyping

►Prevalence of Prevalence of tcdCtcdC deletions (and deletions (and association with severity)association with severity)

End points – POCT End points – POCT PerspectivePerspective

►Acceptability and ease of use of platform – assessed by questionnaire to end-users

►Turnaround time of test – assumed to be time of PCR test duration

►collected by research nurse compared with a matched set of non study subjects (positive and negative) from time of test being ordered to time of result being released.

End points – Disease End points – Disease PerspectivePerspective

►Severity of CDI. Severity of CDI. AA

ggee aanndd llooccaattiioonn mmaattcchheedd ccaasseess

►Complications Complications PP

MMCC,, CCoolleeccttoommyy eettcc

►All cause mortality / mortality related to CDIAll cause mortality / mortality related to CDI

►Length of StayLength of Stay

Hands on time: approx 2 minutesTime to final result: approx 45 minutes

Test timeTest time

Raw Sample and Buffers Raw Sample and Buffers are are LoadedLoaded into into

CartridgeCartridge(swab from stool sample) (swab from stool sample)

Sample isSample is Pre filteredPre filtered to removeto remove

large inhibitory debrislarge inhibitory debris

Target OrganismsTarget OrganismsAre Are Isolated,Isolated,

ConcentratedConcentrated and and WashedWashed

Organism is Organism is LysedLysedto release DNAto release DNA

Disposable, enclosedDisposable, enclosedMicro-fluidic CartridgeMicro-fluidic Cartridge

MixtureMixtureDeliveredDelivered to Integrated to Integrated

Reaction Tube for Reaction Tube for Amplification and DetectionAmplification and Detection

With I-CORE ModuleWith I-CORE Module

DNA Molecules Mixed DNA Molecules Mixed with with AmplificationAmplification and and

DetectionDetection Chemicals Chemicals (primers and probes)(primers and probes)

Multiplex real-time PCR

3 Targets (plus internal positive control): ► Toxin B gene Toxin B gene ► Binary toxin Binary toxin ► tcdCtcdC deletion deletion

Patient Admission

Admission stool sample collected (<72 hours)

consent & enrolled into study

Result interfaced with EPR via WinPath. Communicated to clinical team and Infection Control – appropriate management

Symptoms of CDI – POCT PCR GeneXpert&

Positive samples sent to lab for further work

Specimen workflowSpecimen workflow

Positive ResultPositive Result

Story so Story so far…………………………..far…………………………..

IT Issues:IT Issues:Interface Interface

Data Ownership Data Ownership

Network PointsNetwork Points

Staffing Issues:Staffing Issues:Restricted Restricted

RecruitmentRecruitment

BureaucracyBureaucracy

Acknowledgement:Acknowledgement:

► Dr Simon Goldenberg Dr Simon Goldenberg Consultant Microbiologist GSTT Foundation Trust HospitalConsultant Microbiologist GSTT Foundation Trust Hospital

► CepheidCepheid► GSTS PathologyGSTS Pathology