Effect of antibiotic stewardship programmes on Clostridium difficile incidence: a systematic review and meta-analysis

Despite vigorous infection control measures, Clostridium difficile continues to cause significant disease burden. Antibiotic stewardship programmes (ASPs) may prevent C. difficile infections by limiting exposure to certain antibiotics. Our objective was to perform a meta-analysis of published studies to assess the effect of ASPs on the risk of C. difficile infection in hospitalized adult patients. Searches of PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature and two Cochrane databases were conducted to find all published studies on interventions related to antibiotic stewardship and C. difficile. Two investigators independently assessed study eligibility and extracted data. Risk of bias was assessed using the Downs and Black tool. Risk ratios were pooled using random effects models. Heterogeneity was evaluated using the I-2 statistic. The final search yielded 891 articles; 78 full articles were reviewed and 16 articles were identified for inclusion. Included articles used quasi-experimental (interrupted time series or before-after) or observational (case-control) study designs. When the results of all studies were pooled in a random effects model, a significant protective effect (pooled risk ratio 0.48; 95% CI: 0.38, 0.62) was observed between ASPs and C. difficile incidence. When stratified by intervention type, a significant effect was found for restrictive ASPs (complete removal of drug or prior approval requirement). Furthermore, ASPs were particularly effective in geriatric settings. Restrictive ASPs can be used to reduce the risk of C. difficile infection.