Secondary vancomycin prophylaxis during antibiotic re-exposure for the prevention of recurrent Clostridioides difficile infections: a systematic review and Bayesian meta-analysis

Antibiotic re-exposure after an episode of Clostridioides difficile infection (CDI) is common and is a strong risk factor for recurrent CDI (rCDI). Two randomized controlled trials (RCTs) of vancomycin prophylaxis during antibiotic re-exposure were recently published, which we sought to evaluate by meta-analysis.

We updated a recent systematic review search of MEDLINE and Embase via Ovid to 9 March 2026. RCTs of vancomycin during antibiotic re-exposure as secondary CDI prophylaxis were included. Quality was assessed by the Cochrane RoB2 tool. A Bayesian meta-analysis of 56-day rCDI was conducted on the odds ratio (OR) scale using a weakly informative prior. The probabilities of any benefit (i.e. OR < 1) and that the number needed to treat (NNT) was <20 (i.e. risk difference > 5%) were computed from the posterior. The 95% predictive interval (95% PI) was computed, which corresponds to the predicted range of the effect estimate of a future RCT.

Two RCTs at low risk of bias were included, which comprised 102 patients. The pooled OR was 0.61 [95% credible interval (95% CrI) = 0.27-1.40], which corresponded to a probability of any benefit with vancomycin prophylaxis of 88.0% and a probability that the NNT was <20 of 75.9%. The 95% PI was 0.19-2.00.

Based on two small RCTs, there is a reasonable probability that secondary vancomycin prophylaxis during antibiotic re-exposure reduces 56-day rCDI. However, these results remain uncertain as the 95% PI is wide and consequently larger trials are needed.