Effect of Fecal Microbiota Transplantation on Recurrence in Multiply Recurrent Clostridium difficile Infection: A Randomized Trial

Abstract

Background: To date, evidence for the efficacy of fecal microbiota transplantation (FMT) in recurrent Clostridium difficile infection (CDI) has been limited to case series and open-label clinical trials.

Objective: To determine the efficacy and safety of FMT for treatment of recurrent CDI.

Design: Randomized, controlled, double-blind clinical trial. (ClinicalTrials.gov: NCT01703494).

Setting: Two academic medical centers.

Patients: 46 patients who had 3 or more recurrences of CDI and received a full course of vancomycin for their most recent acute episode.

Intervention: Fecal microbiota transplantation with donor stool (heterologous) or patient's own stool (autologous) administered by colonoscopy.

Measurements: The primary end point was resolution of diarrhea without the need for further anti-CDI therapy during the 8-week follow-up. Safety data were compared between treatment groups via review of adverse events (AEs), serious AEs (SAEs), and new medical conditions for 6 months after FMT. Fecal microbiota analyses were performed on patients' stool before and after FMT and also on donors' stool.

Results: In the intention-to-treat analysis, 20 of 22 patients (90.9%) in the donor FMT group achieved clinical cure compared with 15 of 24 (62.5%) in the autologous FMT group (P = 0.042). Resolution after autologous FMT differed by site (9 of 10 vs. 6 of 14 [P = 0.033]). All 9 patients who developed recurrent CDI after autologous FMT were free of further CDI after subsequent donor FMT. There were no SAEs related to FMT. Donor FMT restored gut bacterial community diversity and composition to resemble that of healthy donors.

Limitation: The study included only patients who had 3 or more recurrences and excluded those who were immunocompromised and aged 75 years or older.

Conclusion: Donor stool administered via colonoscopy seemed safe and was more efficacious than autologous FMT in preventing further CDI episodes.

Primary funding source: National Institute of Diabetes and Digestive and Kidney Diseases.

Figure 1

Enrollment and outcomes. Two patients at the Rhode Island site withdrew from the study before randomization. One reported that his CDI had resolved, and the other withdrew after the donor was unable to produce stool on the day of the planned FMT. Three patients in New York were determined to no longer have CDI after further evaluation by the investigator at that site and were withdrawn from the study before randomization. One patient in New York was found to have colon cancer (an exclusion criterion) at the time of the FMT colonoscopy and was withdrawn from the study. CDI = Clostridium difficile infection; FMT = fecal microbiota transplantation; IBD = inflammatory bowel disease; IBS = irritable bowel syndrome.

Figure 2

Rates of clinical cure in the intention-to-treat population, overall and by site. Error bars represent 95% CIs. FMT = fecal microbiota transplantation.

Figure 3

Distribution of phyla in samples from patients initially having donor FMT (top), those initially having autologous FMT (middle), and those having donor FMT after relapse (bottom) at both sites. Less abundant phyla were present at a mean abundance <1.0% among all samples. FMT = fecal microbiota transplantation.