Comparative Efficacy of Vancomycin and Fidaxomicin Regimens for the Prevention of Recurrent Clostridioides difficile Infection: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
Year: 2026
Type: preprint
Study designs: Systematic Review, Meta-Analysis
Abstract: ABSTRACT Background The optimal treatment for first episodes and first recurrences of Clostridioides difficile infections (CDI) is unknown and there is emerging evidence for pulse-and-taper (P-T) regimens. Therefore, we sought to estimate the relative efficacy of treatment options. Methods MEDLINE and CENTRAL were searched from database inception to September 11, 2026. Randomized controlled trials (RCTs) on the treatment of first episodes or first recurrences of CDI comparing fixed-dose or P-T regimens of fidaxomicin or vancomycin were included. The primary and secondary outcomes were 40-and 56-day CDI recurrence, respectively. A random-effects network meta-analysis on the risk ratio (RR) scale was conducted using a standard regimen (10-14 days) of vancomycin as the comparator. Treatments were ranked using the surface under the cumulative ranking curve (SUCRA). Results 8 RCTs were included, comprising 2120 patients. For 40-day recurrence, fidaxomicin P-T had the highest probability of ranking best (RR=0.10, 95%Confidence Interval [95%CI]=0.03-0.33, SUCRA=0.99), followed by vancomycin P-T (RR=0.40, 95%CI=0.25-0.63, SUCRA=0.66), fixed-dose fidaxomicin (RR=0.63, 95%CI=0.51-0.78, SUCRA=0.34), and, finally, fixed-dose of vancomycin (SUCRA=0.00). The treatments ranked in the same order for 56-day recurrence, though only 3 RCTs reported on this timepoint and fixed-dose fidaxomicin was no longer significantly better than fixed-dose vancomycin. Conclusion Fidaxomicin P-T and vancomycin P-T were both superior to fixed-dose vancomycin at 40-and 56-days. Head-to-head comparative effectiveness RCTs are needed to quantify their relative effect sizes of and impact on long-term prevention of recurrent CDI.
Source: medRxiv
Authors: Connor Prosty, Guillaume Butler-Laporte, James M. Brophy, Émilie Bortolussi-Courval, Charles Frenette, Vivian G. Loo, Susy S. Hota, Yves Longtin, Ling Y. Kong, Matthew P. Muller, Theodore S. Steiner, Louis Valiquette, Nick Daneman, Peter Daley, Caroline Nott, Derek R. MacFadden, Christopher E Kandel, Yan Chen, Santiago Perez-Patrigeon, Todd C. Lee, Emily G. McDonald
Institutions: McGill University, Jewish General Hospital, Lady Davis Institute for Medical Research, University Health Network, University of Toronto, University of British Columbia, Université de Sherbrooke, Memorial University of Newfoundland, University of Ottawa, Ottawa Hospital Research Institute, Toronto East General Hospital, Queen's University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7169525421