PREVENTION OF CLOSTRIDIUM DIFFICILE INFECTION

Abstract

Clostridium difficile infection (CDI) prevention is of high priority. We reviewed clinical practice guidelines (CPGs), and conducted an individual participant data meta-analysis (IPMDA) of randomized controlled trials (RCTs) to assess effectiveness and safety of probiotic prophylaxis. For CPGs, we rated quality, summarized recommendations with their strength and author-reported evidence, then re-evaluated evidence. For the IPDMA, we pooled RCTs investigating probiotics versus control for CDI prevention among antibiotic consumers, using generalized linear mixed models. Our outcomes were CDI and serious adverse events (SAEs). We adjusted for age, sex, hospitalization status, and exposure to high risk antibiotics. We assessed study risk of bias and confidence in estimates of effect. Five international guidelines were evaluated, and all scored poorly for applicability, stakeholder involvement, and rigor of development. Recommendations were not always linked to evidence, and guideline authors were not transparent about how evidence limitations impacted their decisions. None of the guidelines recommended probiotics. Fourteen studies contributed data, with one pending. Probiotics reduced CDI among all studies and the adjusted model. No covariates were significantly associated with CDI. Subgroups suggested that high incidence did not affect probiotic effectiveness, and high-dose, multi-strain probiotics were more beneficial. Our estimate was robust to sensitivity analyses. Probiotics did not significantly affect SAE odds among all studies and the adjusted model. Increasing age was a significantly associated with SAEs. No SAEs were reportedly probiotics-related. For both outcomes, estimates were similar from data of obtained and not obtained studies. Confidence in estimates was moderate for both outcomes, due to low event rates. Current guidelines on CDI prevention did not adhere well to validated standards for development and reporting, most notably due to insufficient links between recommendations and supporting evidence. Our preliminary analysis suggests that probiotic prophylaxis is useful and safe for CDI prevention.