Saha, Srishti

Abstract Background Fecal microbiota transplantation (FMT) cures ~90% of patients with recurrent Clostridioides difficile infection (rCDI). Ongoing or repeated exposure to risk factors, especially antibiotics (a modifiable risk factor but often necessary), may lead to future CDI. However, it is not known if FMT provides durable protection against future CDI despite subsequent antibiotic exposure. We studied the long-term durability of FMT against antibiotic exposure post-FMT. Methods A retrospective cohort study of patients undergoing FMT via colonoscopy for rCDI from Sep 2012 - Jun 2018 was performed. Patients were followed up for 1 year after FMT; data regarding future CDI episodes (watery diarrhea with positive stool test after interim symptom resolution), healthcare exposure, systemic non-CDI antibiotics and acid blocker therapy were collected. Primary outcome was ‘durability’ of response to FMT (defined as no CDI within 1 year post-FMT). Descriptive statistics, Chi square test, Wilcoxon test and multivariate logistic regression were used as appropriate. Results The study included 460 patients; median age 57 years (range 18–94 years), 65.2% (300) female. Overall 31.6% (144) received antibiotics; median number of courses of antibiotics, 2 (range 1–7). Of those who received antibiotics, the incidence of future CDI was 24.3% (n = 34), compared with 9% (n = 28) of those who did not receive antibiotics (P < .001). Median time to first CDI episode post-FMT was 103 (range 5–338) days. Incremental antibiotic courses did not lead to increased risk of future CDI (comparing 1, 2 or ≥3 courses, p = .68). In patients with antibiotic exposure, age and risk factors were similar in patients with and without future CDI (Table 1). Amongst those without antibiotic exposure, inflammatory bowel disease (IBD) predicted future CDI (p = .02). After controlling for risk factors and comorbidities, antibiotic use (p = .004) and IBD (p = .02) independently increased risk of future CDI. Conclusion The majority of patients with rCDI have a durable response to FMT despite ongoing risk factors. These data suggest that three-fourth of patients who receive antibiotics after FMT do not develop future CDI. IBD and antibiotic exposure independently increase the risk of future CDI. Disclosures All authors: No reported disclosures.

INTRODUCTION: Currently, surgery is the primary treatment option for refractory, severe-complicated Clostridioides difficile infection (CDI) in the inpatient setting. There are limited series reporting the efficacy of Fecal Microbiota Transplantation (FMT) to treat such cases as an alternative to surgery or in patients who are not surgical candidates. We aimed to assess the response rate and prognosis of these patients after inpatient FMT. METHODS: We conducted a retrospective chart review of patients with CDI (watery diarrhea with positive stool assay) admitted in the ICU, and who received FMT from January 2013 to July 2016. Potential cases were identified by diagnosis codes and eligibility was confirmed through manual chart review. Severe-complicated CDI was defined as CDI with any of the following: ICU admission, hypotension, shock, sepsis, megacolon, colectomy or death due to CDI. CDI was termed refractory in the absence of clinical response to antibiotics after 5 days. Recurrence was defined as typical CDI symptoms and positive stool assay within 56 days of treatment with interim symptom resolution. The primary outcome was resolution of CDI (clinical cure with no recurrence). Secondary outcomes included risk of recurrent CDI and mortality. Microsoft Excel was used for descriptive statistical analysis. RESULTS: Of 273 patients screened, 6 cases met inclusion criteria. Five patients received FMT via colonoscopy, one via retention enema. The mean age at time of FMT was 72 (range, 54-88) years, 4 (66%) patients were female. All had severe-complicated CDI, 3 had concomitant diverticulosis and none had inflammatory bowel disease (IBD). The median follow-up after FMT was 8.5 (range, 1-18) months. Three patients received non-CDI antibiotics within 6 months post-FMT, 3 received acid suppression therapy (Table 1). FMT was performed after a median of 3 (range, 1-5) episodes of CDI with a median of 4.5 previous courses of antibiotics (range 2-6 courses) (Table 1). Four of the six patients (66%) had resolution of CDI, 2 patients had recurrence. One patient died due to sepsis secondary to CDI; 3 died due to unrelated causes. CONCLUSION: In this small retrospective study, inpatient FMT was effective for treating refractory severe-complicated CDI. There was one CDI-related mortality by the end of follow up. FMT may be an alternative therapy in patients with severe-complicated CDI.

Clostridioides difficile infection (CDI) is a common cause of diarrhea in both inpatient and outpatient settings. The last few years have seen major changes in the treatment spectrum of CDI, most notably, recommendations against using metronidazole for initial CDI, the addition of fidaxomicin and bezlotoxumab, and emergence of microbial replacement therapies. Several other therapies are undergoing clinical trials. This narrative review focuses on the treatment of CDI with a summary of literature on the newer modalities and the treatment guidelines issued by Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases.