The perils of PCR-based diagnosis of Clostridioides difficile infections: painful lessons from clinical trials.

The perils of PCR-based diagnosis of Clostridioides difficile infections: painful lessons from clinical trials. Anaerobe. 2019 Jun 12;: Authors: Kong LY, Davies K, Wilcox MH Abstract Diagnostic tests favoured to detect C. difficile infections (CDI) have undergone successive changes. The problem of over-diagnosis with polymerase chain reaction (PCR) testing is recognized in the clinical setting; here we discuss the parallel of the clinical trial setting. We summarize and discuss four examples of the impact of method used to diagnose CDI on clinical trial outcomes. Bezlotoxumab, a human monoclonal antibody neutralizing toxin B, was found to be protective against recurrent CDI (rCDI) in clinical trials. A post hoc analysis showed that the magnitude of the relative reduction in rCDI rates of bezlotoxumab over placebo in patients diagnosed with toxin-based testing was almost double that in patients diagnosed with PCR. SER-109, a microbiome therapeutic developed to prevent rCDI, showed promise in a phase 1b trial, but results were not replicated in a phase 2 trial in which diagnosis was in majority PCR-based. Surotomycin, an oral lipopeptide antibiotic, was found to be non-inferior to vancomycin in phase 2 study, but development was discontinued after unfavourable phase 3 results in which the majority of CDI were diagnosed by PCR. Finally, a C. difficile vaccine program for a toxoid vaccine developed by Sanofi/Pasteur was terminated after ...
Source: Anaerobe - Category: Microbiology Authors: Tags: Anaerobe Source Type: research