Abstract
BackgroundThe optimum diagnostic test method for Clostridioides difficile infection (CDI) remains controversial due to variation in accuracy in identifying true CDI. This post hoc analysis examined the impact of CDI diagnostic testing methodology on efficacy outcomes in phase 3 MODIFY I/II trials.MethodsIn MODIFY I/II (NCT01241552/NCT01513239), participants received bezlotoxumab (10 mg/kg) or placebo during anti-CDI treatment for primary/recurrent CDI (rCDI). Using MODIFY I/II pooled data, initial clinical cure (ICC) and rCDI were assessed in participants diagnosed at baseline using direct detection methods (enzyme immunoassay [EIA]/cell cytotoxicity assay [CCA]) or indirect methods to determine toxin-producing ability (toxin gene polymerase chain reaction [tgPCR]/toxigenic culture).ResultsOf 1554 participants who received bezlotoxumab or placebo in MODIFY I/II, 781 (50.3%) and 773 (49.7%) were diagnosed by tgPCR/toxigenic culture and toxin EIA/CCA, respectively. Participants diagnosed by toxin EIA/CCA were more likely to be inpatients, older, and have severe CDI. In bezlotoxumab recipients, ICC rates were slightly higher in the toxin EIA/CCA subgroup (81.7%) vs tgPCR/toxigenic culture (78.4%). Bezlotoxumab significantly reduced the rCDI rate vs placebo in both subgroups; however, the magnitude of reduction was substantially larger in participants diagnosed by toxin EIA/CCA (relative difference, –46.6%) vs tgPCR/toxigenic culture (–29.1%). In bezlotoxumab recipients, the rCDI rate was lower in the toxin EIA/CCA subgroup (17.6%) vs tgPCR/toxigenic culture (23.6%; absolute difference, –6.0%; 95% confidence interval, –12.4 to 0.3; relative difference, –25.4%).ConclusionsDiagnostic tests that detect fecal C. difficile toxins are of fundamental importance to accurately diagnosing CDI, including in clinical trial design, ensuring that therapeutic efficacy is not underestimated.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
