Using PCR in place of GDH as the first line assay in a two-step CDI testing algorithm – evidence of help not hindrance from samples processed at clinical microbiology laboratories in Wales

Abstract

Background Guidance recommends the use of a two-stage algorithm for diagnosis of Clostridioides difficile infection (CDI) utilising either PCR or a glutamate dehydrogenase (GDH) assay as the first line screen. There is ongoing debate as to whether PCR is a hindrance due to fear of over-diagnosis. Methods Between December 2017 and March 2019 over 65,000 tests for CDI were undertaken in Wales. PCR (Serosep EntericBio C. difficile assay) was employed as the first line test for 36% of samples with the remainder tested using a GDH assay (Techlab C. diff ChekTM -60). Positive samples were tested using a toxin EIA (Techlab Tox A/B Quik Chekò). Culture (alcohol shock & CCEY; Oxoid) and capillary electrophoresis PCR ribotyping were undertaken at the UK Anaerobe Reference Unit (UKARU). Results The proportion of samples testing positive using PCR and GDH was 5.2% and 8.3% with a toxin EIA positive percentage of 30% and 25% respectively. Of these samples 73% (n=2543) of GDH and 80% (n=974) of PCR positive samples were referred for culture and ribotyping. No C. difficile was isolated from 15% of GDH and 10.5% of PCR positive specimens. Non-toxigenic strains were isolated from 6.6% of GDH and 0.2% of PCR positive samples and approximately equal proportions of both GDH and PCR positive samples were ribotyped (60% vs. 63% of 2125 samples). Conclusions There was no evidence of increased ascertainment of CDI using PCR. In fact, culture and ribotyping demonstrated an improved specificity for PCR that is helpful for accurate CDI diagnosis.