Fecal Microbiota Transplantation for Recurrent Clostridium Difficile Infection in Pediatric Patients With Refractory Inflammatory Bowel Disease

Introduction: The incidence and severity of Clostridioides difficile infection (CDI) have been increasing over the past decades. It particularly contributes to acute exacerbations and worsen the severity of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) is one of standard treatments for recurrent CDI. The aim of this study was to evaluate the clinical outcome of FMT for recurrent CDI in pediatric patients with refractory IBD. Methods: From May 2013 through April 2023, we retrospectively reviewed the clinical characteristics and treatment outcomes of pediatric patients with IBD who were treated for recurrent CDI with FMT at the Seoul National University Bundang Hospital. Data on clinical characteristics, endoscopic findings, pathologic findings, and long-term outcomes of patients with refractory IBD were retrospectively collected and analysed. Results: A total 18 patients with refractory IBD and recurrent CDI were included in the study, among which 8 had ulcerative colitis, 6 had Crohn’s disease, and 4 had IBD-unspecified. The median age of patients was 18.5 (12.0-23.0) years, median duration of IBD before FMT was 5.0 (1.0-9.7) years, and median follow-up after FMT was 2.2 (0.3 – 5.8) years. Patients received FMT ranging from one to four times, and the median number of CDI episodes before receiving FMT was 2 (0-9). After FMT, the overall eradication rate of CDI was 90%, the mucosal healing rate was 90%, and the remission rate of IBD was 66.7%. Compared to the baseline fecal calprotectin levels (5900 [586 – 6000]), there was a statistically significant decrease in fecal calprotectin levels at 3 days (1932 [194 – 6000]), 1 month (994 [36- 6000]), and 6 months (382 [13 – 6000]) after FMT (P = 0.001). Adverse events were observed in 3 of 18 (16.7%) patients, including one case of IBD flare, one case of infective colitis, and one case of rectal bleeding. Conclusion: FMT was effective not only for the treatment of recurrent CDI but also for the improvement of disease activity of pediatric IBD. Furthermore, since no serious adverse events were observed, FMT may be a safe treatment option for refractory IBD (see Figure 1 and Table 1).Figure 1.: Fecal calprotectin changes after fecal microbioota transplantation. Table 1. - Overall (n=18) Age(y), median (range) 18.5 (12.0-23.0) Sex, female (%) 10 (55.6%) Ulcerative colitis 8 E1 1 E2 2 E3 5 Crohn's disease 6 L1 0 L2 0 L3 5 L4 1 IBD-U 4 Duration of IBD (y), median (range) 5.0 (1.0-9.7) Interval between diagnosis and FMT (m), median (range) 15.5 (5.0-77.0) FMT indication Refractory IBD 7 Refractory IBD with recurrent CDI 11 Number of FMT in single patients 1 10 2 5 3 1 4 2 IBD therapies before FMT 5-ASA 3 Corticosteroids 2 Immunomodulators (MTX) 15 Biologicals Infliximab 9 Adalimumab 5 Ustekinumab 1 Vedolizumab 1 CDI episode before FMT, n (range) 2 (0-9) Prior metronidazole treatment, n (range) 1 (0-7) Prior vancomycin treatment, n (range) 1 (0-3) Related donors, n (%) 0 (0%) Adverse events, n (%) Abd pain 3 (10.0%) Fever 1 (3.3%) Rectal bleeding 1 (3.3%) Diarrhea 1 (3.3%) FMT outcome C.difficile eradication rate, n (%) 9 (90%) Mucosal healing rate, n (%) 9 (90%) IBD remission rate, n (%) 10 (66.7%) IBD, inflammatory bowel disease; CDI, clostridioides difficile infection; IBD-U, inflammatory bowel disease unspecified; FMT, fecal microbiome transplantation; MTX, methotrexate.