Comparative effectiveness of vancomycin and metronidazole on event-free survival after initial infection in patients with Clostridioides difficile - a German multicentre cohort study (IBIS).

The objective of this study is to examine the comparative effectiveness of vancomycin and metronidazole in a confirmatory analysis of event-free survival (EFS) following initial infection in patients with Clostridioides difficile (C. difficile) from a German multicentre cohort study. The IBIS multicentre cohort enrolled patients with an index episode of CDI between August 2017 and September 2020. The primary endpoint was EFS, defined as response to treatment with metronidazole or vancomycin within ten days of initiation, absence of recurrence and death from any cause up to 90 days post-treatment. A Cox proportional hazards model with inverse probability of treatment weighting was used to investigate the comparative effectiveness of this outcome. Additionally, subgroup analyses were performed based on severe and non-severe infections. Of the 489 patients included, 118 (24%) received initial treatment with metronidazole and 371 (76%) with vancomycin. Of these, 78/118 (66.1%) and 247/371 (66.6%), respectively, responded to treatment within ten days, neither developed a recurrence nor died within 90 days and thus achieved the outcome of EFS. In the subgroup of non-severe infections, 74/293 patients (25.3%) received metronidazole, and 219/293 (74.7%) received vancomycin. Of these, 33/74 (44.6%) metronidazole patients and 150/219 (68.5%) vancomycin patients survived event-free. The Cox proportional hazards model revealed differences in EFS for the overall population and both sub-groups (reference metronidazole: all severity levels: hazard ratio [HR] 0.46, [95% Cl 0.33-0.65]; non-severe: HR 0.39; [95% Cl 0.24-0.60]; severe: HR 0.52; [95% Cl 0.28-0.95]). Our analysis confirms current changes in guidelines, as it supports the superiority of vancomycin compared to metronidazole across all severity levels.

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Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement J. Conrad, K. Giesbrecht, R. Cruz Aguilar, A.Ullah, K.-P. Hunfeld, S. Pützfeld, M. Schmitz-Rode, E. Schalk, T. Schmidt-Wilcke, S. Schmiedel, P. Solbach, have no conflict of interest. C. Lübbert received personal consulting fees and speaker fees from Tillotts Pharma. P. Reuken received speaker fees from CSL Behring, Pfizer/BMS, Bristol Meyers Squibb and Astra Zeneca aswell as Support for attending meetings from Gilead. P. Reuken participated in the Advisory Board for Pfizer (Post-COVID 2024) and Gilead (HDV 2023). M.J.G.T. Vehreschild received grants from MSD, Heel, BioNTech, and Roche, and consulting fees from MaaT, Tillotts, MSD/Merck, Roche, and EUMEDICA. M.J.G.T. Vehreschild obtained speaker fees from Merck/MSD, 3M, Ferring, Astellas, Uniklinik Karlsruhe, Uniklinik Köln, Akademie für Infektionsmedizin, Klinikum Essen, Pfizer, Universitätsklinikum Heidelberg, Uniklinik Frankfurt, Landesärztekammer Hessen, Janssen, Institute Merieux, Forum für medizinische Fortbildung GmbH, Universitätsklinikum Freiburg, Berliner Dialyseminar, ADKA, Falk Foundation, St. Johannes Hospital, DiaLog Service, CED Service, Ärztekammer Niedersachsen, St. Josef Hospital, Limbach Gruppe SE, SUMIT OXFORD Ltd., EUMEDICA, KIT Kongress, Tillotts Pharma, Helios Kliniken, Lahn-Dill-Kliniken, Gilead, and Klinikum Leverkusen.