Faecal Microbiota Transplant Decreases Mortality in Severe and Fulminant Clostridioides difficile Infection in Critically Ill Patients

Emily N. Tixier; Elijah Verheyen; Ryan C. Ungaro; Ari M. Grinspan


Aliment Pharmacol Ther. 2019;50(10):1094-1099. 

In This Article

Materials and Methods

We performed a retrospective matched cohort study of patients hospitalised with severe or fulminant CDI who received antibiotics plus FMT or SOC in a single urban tertiary care academic medical centre between 1 December 2013 and 31 August 2018. CDI was defined as diarrhoea with a positive stool test for C difficile (PCR or toxin). The strain of C difficile was not reported as this is not routine practice at our institution. Severity was classified by 2017 IDSA/SHEA guidelines.[3] Severe colitis was defined by white blood cell (WBC) count of ≥15 000 cells/mL or a serum creatinine of >1.5 mg/dL. Fulminant colitis was defined by presence of hypotension or shock, ileus, or toxic megacolon. Serious adverse events were defined as life-threatening events including bacteraemia, aspiration and perforation related to FMT that required medical or surgical intervention.

We identified all patients with severe or fulminant CDI who received critical care in an intensive care or step-down unit during their admission. Therapy plan for CDI was determined by the treating physicians, but all patients received oral vancomycin. Within this group, patients who received FMT were matched 1:2 to SOC patients. SOC was defined as oral vancomycin with or without intravenous metronidazole. No patients received fidaxomicin, bezlotoxumab or other adjunctive therapy. Frozen FMT (donor-selected or OpenBiome) was administered via colonoscopy or flexible sigmoidoscopy. If pseudomembranous colitis was identified during endoscopy, FMT was repeated every 3–5 days until resolution of colitis per previously published protocol.[14,15] Matching was performed by the statistical software based on age, sex, history of CDI in prior 60 days, antibiotic use and CDI severity. Mortality was not known during the matching process. Patient information was extracted from the hospital electronic medical record, including age, sex, comorbidities using the Charlson comorbidity index (CCI),[16] number of prior C difficile episodes, interventions, serious adverse events and relevant dates (eg date of birth, admission, diagnosis of CDI, date of FMT, discharge and death). We also calculated the predicted risk of mortality from CDI using the Clostridium difficile associated risk of death score (CARDS).[17] The exclusion criteria included age <18 years and the absence of vancomycin treatment.

The primary outcome was death during hospital admission. Secondary outcomes included colectomy during admission, recurrent CDI, hospital readmission, and 30- and 90-day mortality rate after discharge. Descriptive statistics were performed using means, standard deviations (SD) and proportions for continuous and categorical data respectively. Associations were assessed using Student's t test, chi-squared test or Fisher's exact tests. Univariable and multivariable logistic regression analyses were performed with odds ratios (OR) and 95% CI reported. For multivariable analysis, age and CCI were a priori entered into models assessing the primary outcome as well as any baseline variable significant at the P < .1 level. Two-sided P < .05 were considered statistically significant. Given that our cohort contained both severe and fulminant patients, we conducted sensitivity analyses to investigate the impact of FMT within the fulminant cases. Analyses were performed using SAS v9.4 (Cary, NC).