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.

Background and Aims: Clostridium difficile infection (CDI) has been associated with an increased mortality risk among patients with inflammatory bowel disease (IBD) in multiple observational studies. We performed a systematic review and meta-analysis to help clearly define the magnitude of risk in IBD patients with and without CDI, and to assess the risk in individual IBD subtypes. Methods: A systematic search of multiple electronic databases was conducted for observational studies reporting the risk of mortality in IBD, stratified by the presence of CDI. Weighted summary estimates were calculated using generalized inverse variance with random-effects model. Study quality was assessed using the Newcastle-Ottawa scale. Results: Ten observational studies were identified (8 from North America and 2 from Europe) and included 40,700 IBD patients with CDI and 1,320,764 IBD controls without CDI. Overall, IBD patients with CDI had a higher risk of mortality compared with IBD patients without CDI [odds ratios (OR), 4.39; 95% confidence interval (CI), 3.56-5.42; I 2=93%]. The results were stable in high-quality studies and in hospitalized patients. When patients were stratified by IBD type, CDI was associated with increased mortality in patients with ulcerative colitis (7 studies) (OR, 4.39; 95% CI, 3.44-5.61; I 2), but not in patients with Crohn’s disease (4 studies) (OR, 2.21; 95% CI, 0.84-5.77; I 2). Individual studies were limited by an inability to control for IBD disease activity and therapeutic interventions. Conclusions: On the basis of 10 observational studies with at least moderate quality, CDI seems to increase mortality risk in IBD, particularly in ulcerative colitis. These findings are a cause for concern and suggest that CDI should be managed aggressively in patients with IBD.