Charles Du, MD1, Yuying Luo, MD2, Samantha Walsh, MLS, MA1, Ari M. Grinspan, MD3; 1Mount Sinai, New York, NY; 2Icahn School of Medicine at Mount Sinai, New York, NY; 3Mount Sinai Hospital, New York, NY
Introduction: Clostridioides difficile infection (CDI) is the most common healthcare-associated infection in the United States, and 25% of patients experience recurrence. Fecal microbiota transplantation (FMT) via colonoscopy has established efficacy and safety data in treating multiple recurrences of CDI, but efficacy of oral FMT capsules is not as well studied. We performed a systematic review with meta-analysis to further examine the efficacy and safety of oral FMT capsules for recurrent CDI. Methods: Studies with ≥ 10 patients that evaluated efficacy of oral FMT capsules specifically for recurrent CDI were queried from MEDLINE, EMBASE, Web of Science, Clinicaltrials.gov, American College of Gastroenterology Abstract Archives, and Open Forum Infectious Diseases until January 1st, 2020. Studies were screened for inclusion by two reviewers independently. Cure rates were pooled by a random effects model and assigned inverse variance weights and Clopper-Pearson confidence intervals. Outliers were identified. Publication bias was assessed with Egger’s test. Heterogeneity was assessed by Q-test and quantified with the I2 statistic. Results: Following independent screening by 2 reviewers (kappa = 0.62), 17 studies encompassing 813 patients were identified for inclusion. Significant variability existed in baseline patient characteristics and protocols regarding type of C. difficile stool tests, capsule preparation, and pre-FMT antibiotic use (Table 1). Meta-analysis of proportions showed efficacy of oral FMT capsules was 0.82 (95% CI 0.77-0.87) (Figure 1). There was significant heterogeneity by Q test (Χ2= 39, p < 0.01) with I2 of 0.59. Of note, the 2016 phase II trial of SER-109 was a significant outlier (p < 0.05). No evidence for publication bias was found (z = -0.09, p = 0.92). Moderator analysis found no difference between oral FMT capsules used for CDI treatment versus recurrence prevention (p = 0.38) nor between frozen and lyophilized preparations (p = 0.39). A total of 16 serious adverse events leading to death or hospitalization were noted: 12 were deemed unrelated to FMT, and 4 were treatment failures leading to hospitalization for recurrent CDI. Discussion: Oral FMT capsules for recurrent CDI are promising due to ease of administration and non-invasive delivery. We found an overall efficacy rate of 82% with a low rate of serious adverse events. Standardized reporting of oral FMT capsule studies is needed to standardize protocols and outcomes (Table 2).
Figure 1: Forest plot demonstrating overall cure rates of oral FMT capsules for recurrent CDI
Table 1: Characteristics of studies of oral FMT capsules for recurrent CDI
Table 2: Proposal for standardized reporting on studies of oral FMT capsules for recurrent CDI
Disclosures: Charles Du indicated no relevant financial relationships. Yuying Luo indicated no relevant financial relationships. Samantha Walsh indicated no relevant financial relationships. Ari Grinspan indicated no relevant financial relationships.