Colonoscopic or Capsule Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection: A Prospective Cohort.

BACKGROUND AND AIMS: Fecal microbiota transplant (FMT) is effective for preventing recurrent Clostridioides difficile infection (rCDI). Prior studies suggest that capsule and colonoscopic FMT administration are similarly effective, although the studies may be limited by small sample size or selection bias. The aim of this study was to compare the CDI recurrent rates following capsule or colonoscopic FMT. METHODS: Prospective cohort of patients with rCDI treated with capsule or colonoscopic FMT between 7/1/19 and 11/29/23. This study's primary outcome was 1-month CDI recurrence rates. Predictors of recurrence were assessed using multivariate logistic regression. RESULTS: Overall, 652 individuals received FMT (421 capsule, 223 colonoscopy). Those receiving capsule FMT were older (median 70 vs 59 years, P < .001). At 1 month, CDI recurrence was higher with capsule compared to colonoscopic FMT (18% vs 7.4%, P = .001). On multivariate analysis, capsule FMT was associated with increased rCDI risk (adjusted odds ratio [OR]: 2.37, 95% confidence interval [CI]: 1.16-5.24, P = .023). Stratified analyses by age showed capsule FMT increased recurrence risk only in patients ≥65 years (OR: 2.7, 95% CI: 1.2-6.4), but not in those <65 years (OR: 2.7, 95% CI: 1.2-6.4). Beyond 1-month, non-CDI antibiotic exposure became the predominant predictor of recurrence. CONCLUSION: FMT by capsule may be associated with higher CDI recurrence compared to FMT by colonoscopy. This effect appears be greater in individuals older than 65 years, thus highlighting the importance of individualized treatment decisions that balance FMT efficacy with procedural risks. Development of microbiota-based therapeutics for CDI should account for the impact of administration route on efficacy.