<i>Clostridium difficile</i> Infection Risk with Important Antibiotic Classes: An Analysis of the FDA Adverse Event Reporting System

<b>Introduction:</b> Antibiotic use is an important risk factor for <i>Clostridium difficile</i> infection (CDI). Prior meta-analyses have identified antibiotics and antibiotic classes that pose the greatest risk for CDI; however, CDI epidemiology is constantly changing and contemporary analyses are needed. <b>Objectives:</b> The objective of this study was to evaluate the association between CDI and important antibiotic classes in recent years using the FDA Adverse Event Report System (FAERS). <b>Methods:</b> FAERS reports from January 1, 2015 to December 31, 2017 were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify CDI cases. We computed the Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95%CI) for the association between antibiotics and CDI. An association was considered statistically significant when the lower limit of the 95%CI was greater than 1. <b>Results:</b> A total of 2,042,801 reports (including 5,187 CDI reports) were considered, after inclusion criteria were applied. Lincosamides (e.g., clindamycin) had the greatest proportion of CDI reports, representing 10.4% of all lincosamide reports. CDI RORs (95%CI) for the antibiotic classes were (in descending order): lincosamides 46.95 (39.49-55.82), monobactams 29.97 (14.60-61.54), penicillin combinations 20.05 (17.39-23.12), carbapenems 19.16 (15.52-23.67), cephalosporins/ monobactams/carbapenems 17.28 (14.95-19.97), cephalosporins 15.33 (12.60-18.65), tetracyclines 7.54 (5.42-10.50), macrolides 5.80 (4.48-7.51), fluoroquinolones 4.94 (4.20-5.81), and trimethoprim-sulfonamides 3.32 (2.03-5.43). <b>Conclusion:</b> All antibiotic classes included in the study were significantly associated with CDI. Lincosamides (e.g., clindamycin) had the highest CDI ROR among the antibiotics evaluated in this study.