Improving Clinical Outcomes of Encapsulated Faecal Microbiota Transplantation for Clostridioides difficile Infection Through Empirical Donor Selection and Optimised Dosing: A Quality Improvement Study.

BACKGROUND: Faecal microbiota transplantation (FMT) is effective for Clostridioides difficile infection (CDI), but real-world effectiveness data are warranted to refine treatment algorithms. We previously found that FMT effectiveness varied with donors, and the effect of a single capsule FMT administration was lower than expected. AIMS: To improve FMT outcomes through empirical donor exclusion and application of an optimised capsule FMT dosing regimen. METHODS: In this multi-site Danish quality improvement study, we included patients with CDI treated with capsule-based FMT from 24 June 2019 to 30 September 2024. The primary outcome was cure of C. difficile-associated diarrhoea (CDAD) 8 weeks after FMT. We assessed this using statistical process control charts monitored separately for the primary FMT centre and the external FMT sites. We used multivariable, mixed-effect logistic regression analysis to evaluate the impact of FMT dosing while adjusting for patient, donor and CDI-related factors. RESULTS: We included 1176 patients (1707 FMT treatments). At external FMT sites, the cure rate from one FMT treatment changed from 50% (95% confidence interval (CI): 45%-56%) to 59% (55%-63%) following the exclusion of three low-performing donors in November 2022. After implementing a two-dose capsule FMT dosing regimen in February 2024, the cure rate increased to 72% (65%-77%). The impact of the two-dose capsule FMT dosing regimen remained statistically significant after adjustment (odds ratio 1.22; 95% CI 1.16-1.28; p < 0.001). CONCLUSION: Empirical donor selection and a two-dose capsule FMT regimen improved clinical outcomes in a large-scale system treating patients with CDI.