Toxin independent biomarker for detection of clostridium difficile (U245)

Tuesday, 25 October 2016

Ulster University have developed and clinically validated a novel Clostridium difficile (C. difficile) diagnostic test.  The “Ulster C. difficile Assay” is a rapid in vitro diagnostic test for the direct, qualitative detection of C. difficile in human liquid or soft stool specimens from patients suspected of having C. difficile infection (CDI).  The test, based on real-time PCR technology is intended for use as an aid for diagnosis of CDI.

Problem Being Solved

C. difficile associated diarrhoea (CDAD) is a life threatening disease, with an attributable mortality of 6 to 15%. CDAD has become more common and may also be increasing in severity [1].  There remains an urgent need to control this infection in hospitals, where it frequently afflicts the most vulnerable patients who receive antibiotic therapies for complicated infections. C. difficile infections impose a significant burden on healthcare budgets.  It has been estimated that in the USA, C difficile costs $59,153 per hospital stay and cost the US Medicare system $5.6 billion in 2007 alone. The global C. difficile testing market is estimated to be worth $200m annually.  Ulster University have developed and validated the “UU C. difficile Assay” to aid patient management and reduce the clinical and cost burden associated with CDI.

Technology

 The “UU C. difficile Assay” is a real-time PCR assay that detects the presence of 2 genes specific to C. difficile.  The presence of the tcdB (toxin B) gene is specific to toxigenic strains of C. difficile, while the gene CD3609 is a specific biomarker expressed by both toxigenic and non-toxigenic strains of C. difficile.

Clinical Performance:

 The clinical accuracy of the “UU C. difficile Assay” was determined in a blinded investigational study analysing anonymised stool samples from Antrim Area Hospital against the current Antrim Area Hospital C. difficile diagnostic protocol.  A total of 100 stool specimens were analysed for C. difficile by the “UU C. difficile Assay” and 97 valid test results were compared to the results generated by the Antrim Area Hospital protocol (Techlab C. difficile Quik Chek GDH and Tox A/B assays, followed by Cepheid C. difficile Xpert/epi for GDH +ve, Tox A/B –ve patient samples).

 

 

 

 

QuikChek C. difficile Complete Assay

Cepheid C. difficile Xpert/epi

GDH

Tox A/B

Samples Tested

97

97

36

“UU Assay” Concordance

91/97

72/97

33/36

“UU Assay” Discordance

6/97*

25/97**

3/36

 

 

* In the 6 discordant samples the “UU C. difficile Assay” identified 5 samples that were negative by GDH assay, as containing C. difficile, 2 of which were identified as toxigenic strains.

 

** Out of 25 discordant samples, 23 were subsequently retested in Antrim with Cepheid Xpert/epi assay and all (23/23) were determined to contain toxigenic C. difficile thus supporting the UU Assay result.

 

Table 1.  Comparison of the “UU C. difficile Assay’s” clinical accuracy with competitor tests.

 

Overall the “UU C. difficile assay”;

 

·         Reported 7 discordant clinical results compared to the Antrim Area Hospital protocol.

 

·         Demonstrates greater clinical accuracy than the QuikChek C. difficile Complete Assay (GDH/ToxA/B).

 

·         Demonstrates greater analytical sensitivity than the Cepheid C. difficile Xpert/epi assay.

 

Benefits/Applications

The UU C. difficile Assay” has the following advantages over existing C. difficile diagnostic protocols:

              “one step” test – reducing time to obtaining clinically actionable results.

              Detects the presence of C. difficile with greater sensitivity and specificity than other competing tests.

              Reduces false negative and false positive results

              Distinguishes toxigenic and non-toxigenic C. difficile.

 

Publications:

 

 

Gerding et al.  Measures to control and prevent Clostridium difficile infection.  Clin Infect Dis 2008; 46 (s1): s43-49.

 

Opportunity/Partnership Sought

Ulster is actively seeking a strategic partner to assist in the further development of this C. difficile diagnostic assay providing a route to market for the safe and effective treatment of C. difficile associated diarrhoea.  The University is open to a variety of models for collaboration including sponsored research, out-licensing and co-development.

In addition, the inventors of this technology are able to provide valuable know-how in order to assist with its successful commercialisation.

For more information please contact:

 

Dr Oonagh Lynch

Technology Commercialisation Executive

Research & Impact

Tel: +44 (0) 28 9036 6707

Mob: +44 (0) 77 6536 3191

Email:ot.lynch@ulster.ac.uk