Gut Bugs for C. Difficile Infection

Background: Clostridioides difficile infection is the commonest cause of drug treatment-induced infectious diarrhea, which is often recurrent with high mortality. Current treatments mainly include antibiotics, which have low sustained cure rates of 30-35%. Therefore, alternative or additive treatments are required. Hypothesis: In the treatment of the first recurrent or refractory Clostridioides difficile infection, FMT alone leads to a greater sustained cure rate than oral vancomycin hydrochloride treatment alone but to a comparable rate to vancomycin hydrochloride plus FMT combination. Design: Randomized controlled trial that will allocate participants in a 1:1:1 ratio to one of three groups: (1) FMT alone, (2) vancomycin alone, and (3) vancomycin followed by FMT. Groups 1 and 2 will be double-blinded because these are the primary outcome comparison groups. Group 3 will remain unblinded because the treatment days differ, and there is no justifiable reason to blind them. Participants: Eighty-four people aged 16-90 diagnosed with recurrent or refractory Clostridioides difficile infection who can swallow capsules. Donors: Eight healthy donors aged 16-40 years who pass a strict screening process. Interventions: FMT capsules vs vancomycin hydrochloride capsules vs vancomycin hydrochloride capsules, followed by FMT. Assessments: Data on treatment response, gut symptoms and composition, well-being, quality of life and safety will be collected over 12-weeks. Assessment measures include a clinical evaluation, the Bristol Stool Chart, the Gastrointestinal Symptom Rating Scale (GSRS), the Short Warwick Edinburgh Mental Well-Being Scale (SWEMWBS) and the the EQ-5D-5L.. The stool microbiome from donors and participants (baseline and 12 weeks after treatment) will be characterized by metagenomic sequencing.