Tariq, Raseen

Background: Prevention of recurrent Clostridioides difficile infection (CDI) is a challenge in clinical practice, particularly in patients who need systemic antimicrobial therapy. We aimed to evaluate the role of oral vancomycin prophylaxis (OVP) in prevention of primary or future CDI in patients on systemic antimicrobial therapy. Methods: A systematic search of MEDLINE, Embase, and Web of Science was performed from 2000 to January 2020. We included case-control or cohort studies that included patients on systemic antimicrobial therapy who did or did not receive oral vancomycin prophylaxis (OVP) and were evaluated for development of CDI. Odds ratio (OR) estimates with 95% confidence intervals (CI) were calculated. Results: Four studies including 1352 patients evaluated OVP for primary CDI prevention, with CDI occurring in 29/402 patients on OVP (7.4%) compared with 10.4% (99/950) without OVP. Meta-analysis revealed no significant decrease in risk of CDI in patients who received OVP (OR, 0.18; 95% CI, 0.03–1.03; p = 0.06). There was significant heterogeneity with I 2 = 76%. Ten studies including 9258 patients evaluated OVP for secondary CDI prevention. Future CDI occurred in 91/713 patients on OVP (13.3%) compared with 21.9% (1875/8545) who did not receive OVP. Meta-analysis revealed a statistically significant decreased risk of future CDI (OR, 0.34; 95% CI, 0.20–0.59; p < 0.00001). Significant heterogeneity was seen with I 2 = 59%. Discussion: Based on observational data, OVP appears to decrease the risk of future CDI in patients with prior CDI who require systemic antimicrobial therapy. However, OVP was not effective for primary prevention of CDI.

Background and Goals: Clostridioides difficile infection (CDI) recurs in 10% to 15% after fecal microbiota transplantation (FMT). We identify predictors, and describe management and outcome of patients with recurrent CDI after FMT in a predominantly outpatient cohort. Methods: A nested case-control study of patients undergoing FMT for recurrent CDI from August 2012 to January 2017 was performed. FMT failure was defined as recurrent diarrhea with positive C. difficile stool test during follow-up (≥2 mo). Controls (patients without FMT failures) were matched to cases 1:1 for sex and timing of FMT±1 month. Results: Overall, 522 patients underwent FMT; 70 [13.4%; median age 53.8 years (range, 18 to 89 y), 54.3% females] recurred within a median 5.6 months (range, 0.2 to 34.9 mo). Number of prior CDI episodes, prior CDI treatment, and prior CDI-related hospitalizations were similar in cases and controls. Systemic antibiotics after FMT (54.3% vs. 21.4%, P<0.0001), inflammatory bowel disease (IBD) (34.3% vs. 15.7%, P=0.01), pseudomembranes at FMT (4.3% vs. 0%, P=0.03), and poor bowel preparation (68.5% vs. 31.4%, P=0.01) were associated with FMT failure. On multivariate analysis, IBD [odds ratio (OR) 4.34; 95% confidence interval (CI), 1.24-15.15], systemic antibiotics (OR 7.39; 95% CI, 3.02-18.07), and poor bowel preparation (OR 3.84; 95% CI, 1.59-9.28) predicted FMT failure with an area under the curve of 0.78. Among FMT failures, 37 (52.8%) were managed with antibiotics, 32 (45.7%) with repeat FMT after antibiotics and 1 with colectomy. Conclusions: Use of systemic antibiotics, IBD, and poor bowel preparation predict FMT failure. Patients with FMT failure can be managed with antibiotics and/or repeat FMT.

AbstractBackgroundClostridioides difficile infection (CDI) is associated with poor outcomes in inflammatory bowel disease (IBD) patients. Data are scarce on efficacy of fecal microbiota transplant (FMT) for recurrent CDI in IBD patients.MethodsWe reviewed health records of IBD patients (18 years of age or older) with recurrent CDI who underwent FMT. Outcomes of FMT for CDI were assessed on the basis of symptoms and stool test results.ResultsWe included 145 patients (75 women [51.7%]; median age, 46 years). Median IBD duration was 8 (range, 0–47) years, 36.6% had Crohn disease, 61.4% had ulcerative colitis, and 2.1% had indeterminate colitis. Median number of prior CDI episodes was 3 (range, 3–20), and 61.4% had received vancomycin taper. Diarrhea resolved after FMT in 48 patients (33.1%) without further testing. Ninety-five patients (65.5%) underwent CDI testing owing to post-FMT recurrent diarrhea; 29 (20.0%) had positive results. After FMT, 2 patients received empiric treatment of recurrent CDI without symptom resolution, suggesting IBD was the cause of symptoms. The overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1–51) months. Forty-three patients (29.7%) had planned IBD therapy escalation after CDI resolution; none de-escalated or discontinued IBD therapy. Overall, 7.6% had worsening IBD symptoms after FMT that were treated as new IBD flares. No clinical predictors of FMT failure were identified.ConclusionsFew patients had new IBD flare after FMT. Fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.

Introduction: Fecal microbiota transplant (FMT) has been shown to be an effective treatment for recurrent Clostridioides difficile infection (CDI). Immunosuppression is one of the risk factors for CDI. However, most of the trials evaluating efficacy of FMT have excluded immunocompromised patients. Patients with hematological cancers represent a major class of immunocompromised patients. Hence, we performed a meta-analysis to evaluate the efficacy of FMT in patients with hematological cancer for the treatment of recurrent CDI. Methods: A systematic search of Medline, Embase, and Web of Science was performed from January 2000 up to December 2018. Articles included for meta-analysis were case series and case reports that assessed efficacy of FMT in hematological cancer patients were included. Study quality was assessed using the Newcastle-Ottawa scale. The main outcomes were pooled proportions of patients achieving cure after first FMT. The cure rate was defined as resolution of diarrhea without any recurrence. Results: 10 studies (5 case series and 5 case reports) were included in the analysis, making up 29 patients who underwent 38 total FMT procedures. The follow up period ranged from 1- 14 months. Of the included patients, 17 had leukemia, 10 had lymphoma and 2 patients had multiple myeloma and myelodysplastic syndrome each. 7 of these patients had undergone hematopoietic stem cell transplant. The pooled cure rate was 82% [confidence interval (CI) 67-94%] after 1 FMT with no heterogeneity (I2=0%). Minor publication bias was seen on visual inspection of funnel plot. FMT was generally well tolerated by these patients. No serious side effects were reported in any study. One of the studies reported death due to cardiac arrest 5 days after FMT which was thought to be unrelated to the procedure. Mild side effects including mild abdominal pain, transient diarrhea, fecal urgency, constipation and nausea were reported in 5 patients. Conclusion: Based on limited observational data, FMT seems to be an effective and safe modality for management of recurrent CDI in patients with hematological cancers. However, further prospective clinical trials are needed to establish its safety as a first line therapy for recurrent CDI in this population. Figure Disclosures Jamshed: Takeda Pharmaceutical: Honoraria. Khanna:Rebiotix, Inc: Research Funding; Probio Tech, LLC: Consultancy; Facile Therapeutics: Consultancy; Shire, Plc: Consultancy.

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.