There has been an increase in the burden of Clostridioides difficile infection (CDI),1 especially in high-risk populations such as patients with inflammatory bowel disease (IBD).2 The prevalence of CDI in the IBD population is up to 8-fold higher than comparable controls, with increased rates of recurrence and CDI-associated mortality.3 In addition, CDI may induce an IBD flare, and worsen disease severity and clinical course.4

Fecal microbiota transplantation (FMT) is a guideline recommended therapy for recurrent CDI5; however, supportive randomized trials excluded patients with IBD. In retrospective trials of patients with IBD, FMT failure rates had been reported to be approximately 25% to 30%.6 In addition, Khoruts and colleagues reported that patients with IBD and CDI were more likely to fail FMT,7 leading to further uncertainty regarding the safety and efficacy of FMT in IBD patients with concurrent CDI. Accordingly, we conducted the first prospective study examining the efficacy of FMT among patients with IBD and CDI.

Methods
We conducted an open-label, prospective, single-arm, multicenter cohort study at 4 tertiary care FMT referral centers (Brigham and Women’s Hospital, Indiana University, Brown University, and Mount Sinai Hospital; NCT03106844). Patients with a confirmed diagnosis of IBD and 2 or more confirmed CDI episodes within 12 months, including the most recent episode occurring within 3 months, were enrolled. In keeping with CDI clinical guidelines,5 polymerase chain reaction or glutamate dehydrogenase with toxin enzyme immunoassay were permitted for the qualifying CDI episode. Patients with a total or subtotal colectomy, isolated ileal or small bowel Crohn’s disease, those pregnant or breastfeeding, those treated with vancomycin or metronidazole for more than 60 days, or those who had undergone a prior FMT within 12 months were excluded. Baseline IBD and CDI data were collected. All patients underwent a single FMT via colonoscopy. Four robustly screened healthy donors were used (OpenBiome, Cambridge, MA).8

Stool testing, including glutamate dehydrogenase, toxin enzyme immunoassay ,and polymerase chain reaction, was performed 1, 8, and 12 weeks post-FMT regardless of symptoms to assess for CDI and C. difficile colonization rates. All stool testing was performed at a central laboratory. The primary outcome was FMT failure through week 8, defined as diarrhea (3 or more loose stools daily for 3 or more days) and stool testing positive for C. difficile via 2-step testing using glutamate dehydrogenase and toxin enzyme immunoassay. Patients who met the criteria for failure underwent a second FMT. Secondary outcomes included C. difficile colonization defined as patients without diarrhea whose stool remained positive via polymerase chain reaction post-FMT.

Results
Fifty participants were enrolled (August 2017 to October 2019) among whom 15 had Crohn’s disease and 35 had ulcerative colitis (Table 1). The mean age of participants was 43 years (range 21–91) and the cohort was primarily female (58%). A total of 49 patients received treatment. One patient withdrew before treatment and was not replaced. Among the 49 participants, 1 patient was lost to follow-up after the week 1 visit and was treated as an FMT failure. Baseline CDI characteristics: 48% had 2 CDI episodes before entry, among whom 87.5% (21/24) were diagnosed via polymerase chain reaction at the qualifying episode; 38% had 3 confirmed episodes, among whom 78.9% (15/19) were diagnosed via polymerase chain reaction; and 14% had 4 prior CDI episodes among whom 71% were diagnosed via polymerase chain reaction (5/7).