Oral, Capsulized, Frozen Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection

Abstract

IMPORTANCE Fecal microbiota transplantation (FMT) has been shown to be effective in treating relapsing or refractory Clostridium difficile infection, but practical barriers and safety concerns have prevented its widespread use. Copyright 2014 American Medical Association. All rights reserved. OBJECTIVE To evaluate the safety and rate of resolution of diarrhea following administration of frozen FMT capsules from prescreened unrelated donors to patients with recurrent C difficile infection. DESIGN, SETTING, AND PARTICIPANTS Open-label, single-group, preliminary feasibility study conducted from August 2013 through June 2014at Massachusetts General Hospital, Boston. Twenty patients (median age, 64.5 years; range, 11-89 years) with at least 3 episodes of mild to moderate C difficile infection and failure of a 6- to 8-week taper with vancomycin or at least 2 episodes of severe C difficile infection requiring hospitalization were enrolled. INTERVENTIONS Healthy volunteers were screened as potential donors and FMT capsules were generated and stored at -80°C (-112°F). Patients received 15 capsules on 2 consecutive days and were followed up for symptom resolution and adverse events for up to 6 months. MAIN OUTCOMESAND MEASURES The primary end points were safety, assessed by adverse events of grade 2 or above, and clinical resolution of diarrhea with no relapse at 8 weeks. Secondary end points included improvement in subjective well-being per standardized questionnaires and daily number of bowel movements. RESULTS No serious adverse events attributed to FMT were observed. Resolution of diarrhea was achieved in 14 patients (70%; 95% CI, 47%-85%) after a single capsule-based FMT. All 6 nonresponders were re-treated; 4 had resolution of diarrhea, resulting in an overall 90% (95% CI, 68%-98%) rate of clinical resolution of diarrhea (18/20). Daily number of bowel movements decreased from a median of 5 (interquartile range [IQR], 3-6) the day prior to administration to 2 (IQR, 1-3) at day 3 (P =.001) and 1 (IQR, 1-2) at 8 weeks (P