Point of Care Testing – Clostridium difficle Amita Patel Guy’s and St Thomas’ NHS Foundation Trust

Project Aim “Measuring the Clinical Value and impact of C. difficle Point of Care testing (POCT) in ICU and Care of Elderly wards” (Project duration 18 months)

Project Stakeholders

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

Key End Points ► Carriage and likelihood of Infection ► Predictability of virulence ► POCT – as a platform does it work? ► Turnaround times and its impact on Patient

Key End points – Infection ► Measure the prevalence of carriage of (toxigenic and non-toxigenic C. difficile) ► Measure likelihood of developing infection in those that are carriers and, ► Establish if source of infection is endogenous or exogenous

End points – Virulence Perspective ► Reliability of presumptive 027 identification by comparison to PCR ribotyping ► Prevalence of tcdC deletions (and association with severity)

End points – POCT Perspective ► ► 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 Perspective ► Severity of CDI.  Age and location matched cases ► Complications  PMC, Colectomy etc ► All cause mortality / mortality related to CDI ► Length of Stay

Hands on time: approx 2 minutes Time to final result: approx 45 minutes Test time

Raw Sample and Buffers are Loaded into Cartridge (swab from stool sample) Sample is Pre filtered to remove large inhibitory debris Target Organisms Are Isolated, Concentrated Concentrated and Washed Organism is Lysed to release DNA Organism is Lysed to release DNA Disposable, enclosed Micro-fluidic Cartridge Mixture Delivered to Integrated Reaction Tube for Amplification and Detection With I-CORE Module DNA Molecules Mixed with Amplification and Detection Chemicals (primers and probes) (primers and probes)

Multiplex real-time PCR 3 Targets (plus internal positive control): ► Toxin B gene ► Binary toxin ► tcdC 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 workflow

Positive Result

Story so far………………………….. IT Issues: Interface Data Ownership Network Points Staffing Issues: Restricted Recruitment Bureaucracy

Acknowledgement: ► Dr Simon Goldenberg Consultant Microbiologist GSTT Foundation Trust Hospital ► Cepheid ► GSTS Pathology