Predictors and Management of Patients who Failed Fecal Microbiota Transplantation for Recurrent C. difficile Infection

Abstract

Introduction: A fraction of patients have recurrent Clostridium difficile infection (CDI) after fecal microbiota transplantation (FMT). Known predictors include severe-complicated infection and inpatient FMT. We identified predictors and describe management and clinical outcomes of patients who fail FMT in a predominantly outpatient cohort of CDI patients. Methods: A nested case-control study of patients who underwent FMT for recurrent CDI from 08/2012 to 01/2017 was performed. FMT failure was defined as recurrent diarrhea with a positive C. difficile stool test. Cases were patients who had CDI recurrence after FMT and controls were patients with no CDI recurrence. Controls were matched to cases 1:1 for gender and timing of FMT ± 1 month to ensure similar follow-up time. Data including demographics, comorbid conditions, donor information, FMT route, post-FMT antibiotic exposure and post-FMT CDI management were collected. Results: Overall, 522 patients underwent FMT and 70 (13.4%) patients (median age 53.8 years, (range (18-89), 54.3% females) had recurrence within a median of 5.6 months following FMT (range 0.2-34.9 months). There were no differences in number of prior CDI episodes, courses of metronidazole, vancomycin or fidaxomicin prior to FMT, prior CDI related hospitalizations and mode of FMT delivery between cases and controls (Table 1). The use of non-CDI antibiotics after FMT (54.3% vs 21.4%, P<0.0001), presence of IBD (34.3% vs 15.7%, P=0.01), presence of pseudomembranes at FMT (4.3% vs 0%, P=0.03) and poor quality of bowel preparation (28.5% vs 21.4%, P=0.01) were associated with FMT failure. On multivariate logistic regression, IBD (OR 5.1, 95%CI, 1.9-14.2), use of non-CDI antibiotics after FMT (OR 7.8, 95%CI, 3.3-19.8) and poor quality of bowel preparation (OR 3.7, 95%CI, 1.5-9.0) predicted FMT failure, with an area under the curve of 0.78. Of patients who failed FMT, 12 were managed with repeat FMT after 1 antibiotic course, 15 were managed with repeat FMT after 2 antibiotic courses, and 5 with repeat FMT after 3 antibiotic course; 37 (52.8%) were successfully managed with antibiotics (25 vancomycin, 11 fidaxomicin, 1 metronidazole+vancomycin), 1 patient underwent colectomy for severe complicated CDI.Table: Table. Clinical characteristics of cases and controlsConclusion: Use of non-CDI antibiotics, IBD and poor quality of bowel preparation are associated with FMT failure. Patients with FMT failure can usually be managed with repeated courses of antibiotics or repeat FMT after antibiotic therapy.