Frailty level at discharge predicts mortality in older patients with Clostridioides difficile more accurately than age or disease severity.

PURPOSE: Clostridioides difficile infection (CDI) has a high mortality among older patients. Identification of older patients with CDI in increased mortality risk is important to target treatment and thereby reduce mortality. The aim of this study was to investigate mortality rates and compare frailty levels at discharge, measured by the record-based Multidimensional Prognostic Index (MPI), with age and severity of CDI as mortality predictors in patients with CDI diagnosed during hospitalisation. METHODS: This was a population-based cohort study from Central Denmark Region, Denmark, including all patients ≥ 60 years with a positive CD toxin test without prior infection and diagnosed from 1 January to 31 December 2018. Frailty level, estimated from the electronic medical record, was defined as low, moderate, or severe frailty. CDI severity was graded according to international guidelines. Primary outcome was 90-day mortality. RESULTS: We included 457 patients with median age 77 years (interquartile range 69-84) and females (49%). Overall, 90-day mortality was 28%, and this was associated with age (hazard ratio (HR): 2.71 (95% confidence interval 1.64-4.47)), CDI severity (HR 4.58 (3.04-6.88)) and frailty (HR 10.15 (4.06-25.36)). Frailty was a better predictor of 90-day mortality than both age (p < 0.001) and CDI severity (p = 0.04) with a receiver operating characteristic curve area of 77%. CONCLUSION: The 90-day mortality among older patients with CDI in a Danish region is 28%. Frailty measured by record-based MPI at discharge outperforms age and disease severity markers in predicting mortality in older patients with CDI.

Faecal microbiota transplantation for first or second Clostridioides difficile infection (EarlyFMT): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Clostridioides difficile infection is an urgent antibiotic-associated health threat with few treatment options. Microbiota restoration with faecal microbiota transplantation is an effective treatment option for patients with multiple recurring episodes of C difficile. We compared the efficacy and safety of faecal microbiota transplantation compared with placebo after vancomycin for first or second C difficile infection. METHODS: We did a randomised, double-blind, placebo-controlled trial (EarlyFMT) at a university hospital in Aarhus, Denmark. Eligible patients were aged 18 years or older with first or second C difficile infection (defined as ≥3 watery stools [Bristol stool chart score 6-7] per day and a positive C difficile PCR test). Patients were randomly assigned (1:1) to faecal microbiota transplantation or placebo administered on day 1 and between day 3 and 7, after they had received 125 mg oral vancomycin four times daily for 10 days. Randomisation was done by investigators using a computer-generated randomisation list provided by independent staff. Patients and investigators were masked to the treatment group. The primary endpoint was resolution of C difficile-associated diarrhoea (CDAD) 8 weeks after treatment. We followed up patients for 8 weeks or until recurrence. We planned to enrol 84 patients with a prespecified interim analysis after 42 patients. The primary outcome and safety outcomes were analysed in the intention-to-treat population, which included all randomly assigned patients. The trial is registered with ClinicalTrials.gov, NCT04885946. FINDINGS: Between June 21, 2021, and April 1, 2022, we consecutively screened 86 patients, of whom 42 were randomly assigned to faecal microbiota transplantation (n=21) or placebo (n=21). The trial was stopped after the interim analysis done on April 7, 2022 for ethical reasons because a significantly lower rate of resolution was identified in the placebo group compared with the faecal microbiota transplantation group (Haybittle-Peto boundary limit p<0·001). 19 (90%; 95% CI 70-99) of 21 patients in the faecal microbiota transplantation group and seven (33%, 95% CI 15-57) of 21 patients in the placebo group had resolution of CDAD at week 8 (p=0·0003). The absolute risk reduction was 57% (95% CI 33-81). Overall, 204 adverse events occurred, with one or more adverse events being reported in 20 of 21 patients in the faecal microbiota transplantation group and all 21 patients in the placebo group. Diarrhoea (n=23 in the faecal microbiota transplantation group; n=14 in the placebo group) and abdominal pain (n=14 in the faecal microbiota transplantation group; n=11 in the placebo group) were the most common adverse events. Three serious adverse events possibly related to study treatment occurred (n=1 in the faecal microbiota transplantation group; n=2 in the placebo group), but no deaths or colectomies during the 8-week follow-up. INTERPRETATION: In patients with first or second C difficile infection, first-line faecal microbiota transplantation is highly effective and superior to the standard of care vancomycin alone in achieving sustained resolution from C difficile. FUNDING: Innovation Fund Denmark.