S2141 Antibiotic Exposure Is a Short- and Long-Term Risk for Recurrent Clostridioides difficile Infection Following Fecal Microbiota Transplantation

Introduction: Fecal microbiota transplant (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI) after failure of standard therapies. Antibiotic exposure within 2-months post-FMT is a known risk factor for early recurrence. However, the timeline of antibiotics administration later in the post-FMT period and longer-term recurrence remains poorly studied. This study evaluates the association between antibiotic exposure at various intervals within 12 months post-FMT and rCDI. Methods: Secondary analysis of a prospective cohort study included patients with history of rCDI treated with FMT between July 1, 2019 and November 29, 2023 across 6 centers. Follow-up occurred at 1, 2, 6, and 12 months, recording non-CDI antibiotic use and rCDI at each interval; exact dates were unavailable. The cohort was analyzed by follow-up time with individuals who had complete data for that interval. Following CDI recurrence, a participant was excluded from future timepoints. CDI recurrence was defined as laboratory positive testing (per local practice) and resumption of antibiotics for CDI. Results: Of 701 patients in the cohort, 615 met the inclusion criteria, though not all individuals had follow-up at each timepoint. Most patients had 3 or more rCDI episodes prior to FMT. Non-CDI antibiotic administration was associated with CDI recurrence at 1-, 2-, and 12-months, with a trend towards significance at 6-months. Overall, the odds of developing CDI were 3-5 times higher following antibiotic exposure compared to no additional antibiotic exposure. After 1 month, the risk of a spontaneous CDI recurrence (i.e., no additional antibiotic exposures) was <5%. Between 6 and 12 months, all CDI recurrences occurred following 1 or more courses of non-CDI antibiotics. Conclusion: Antibiotic use post-FMT is a key driver of CDI recurrence. Prior studies have identified non-CDI antibiotic exposure as a risk factor for early recurrence (within 2 months). Our cohort replicates this finding, and also demonstrates that antibiotic exposure continues to be a risk for CDI recurrence for at least 1-year post FMT. Recall bias may be a limitation, as patients with recurrence may more readily remember antibiotic use than those without. Overall, our findings support caution in prescribing non-CDI antibiotics for at least a year following FMT for CDI.