Results from the first English stool bank using faecal microbiota transplant as a medicinal product for the treatment of Clostridioides difficile infection

Abstract

Background: Faecal Microbiota Transplant (FMT) has improved outcomes for the treatment of Clostridioides difficile infection (CDI) compared to antibiotic therapy. FMT is classified as a medicinal product in the United Kingdom, similar to the USA and Canada, limiting supply via stool banks without appropriate licencing. In the largest UK cohort to date, we describe the clinical outcomes for 124 patients receiving FMT for recurrent or refractory CDI and present a framework to produce FMT as a licenced medicinal product.

Methods: Anonymous unrelated healthy donors, screened via health assessment and microbiological testing donated stool. In aerobic conditions FMT aliquots were prepared for immediate use or frozen storage, following a production framework developed to comply with Good Manufacturing Practice. Outcome measures were clinical response to FMT defined as resolution of diarrhoea within seven days and clinical cure defined as response without diarrhoea recurrence at 90 days.

Findings: Clinical response was 83·9% (95% CI 76·0%-90·0%) after one treatment. Clinical cure was 78·2% (95% CI 67·4%-89·0%) across the cohort. Refractory cases appeared to have a lower initial clinical response rate compared to recurrent cases, however at day 90 there were no differences observed between these groups.

Interpretation: The methodology developed here enabled successful licencing of FMT by The Medicines and Healthcare products Regulatory Agency as a medicinal product. This has widened the availability of FMT in the National Health Service via a stool bank and can be applied in other centres across the world to improve access to safe and quality assured treatments.

Fig. 1

FMT production in the licenced production facility. (a) weighing out donor faeces into a Nasco-whirl pak filter bag in a class 2 microbiological safety cabinet. (b) homogenisation of stool using a stomacher. (c) aliquoting of prepared FMT into containers for storage. (d) final packaging and labelling of frozen FMT.

Fig. 2

Number of patients receiving FMT and outcomes. ^aOne patient died two days post FMT, with perforated viscus and CDI. Second patient died four days post FMT, from bowel cancer. ^bSix patients were re-treated with a second FMT, of whom four clinically responded to FMT by day 7 and two of these patients demonstrated clinical response without recurrence of disease at day 90.