Real-world Effectiveness of Fecal Microbiota Transplantation for First or Second Clostridioides difficile Infection

Background & Aims: Clostridioides difficile infection (CDI) is associated with high mortality. Fecal microbiota transplantation (FMT) is an established treatment for recurrent CDI, but its use for first or second CDI remains experimental. We aimed to investigate the effectiveness of FMT for first or second CDI in a real-world clinical setting. Methods: This multi-site Danish cohort study included patients with first or second CDI treated with FMT from June 2019 to February 2023. The primary outcome was cure of C. difficile-associated diarrhea (CDAD) 8 weeks after the last FMT treatment. Secondary outcomes included CDAD cure 1 and 8 weeks after the first FMT treatment and 90-day mortality following positive C. difficile test. Results: We included 467 patients, with 187 (40%) having their first CDI. The median patient age was 73 years (interquartile range [IQR], 58–82 years). Notably, 167 (36%) had antibiotic-refractory CDI, 262 (56%) had severe CDI, and 89 (19%) suffered from fulminant CDI. Following the first FMT treatment, cure of CDAD was achieved in 353 patients (76%; 95% confidence interval [CI], 71%–79%) at week 1. At week 8, 255 patients (55%; 95% CI, 50%–59%) maintained sustained effect. In patients without initial effect, repeated FMT treatments led to an overall cure of CDAD in 367 patients (79%; 95% CI, 75%–82%). The 90-day mortality was 10% (95% CI, 8%–14%). Conclusion: Repeated FMT treatments demonstrate high effectiveness in managing patients with first or second CDI. Forwarding FMT in CDI treatment guidelines could improve patient survival. ClinicalTrials.gov, Number: NCT03712722