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

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.

Faecal transplantation for the treatment of Clostridium difficile infection: a review.

Clostridium difficile infection (CDI) remains a major healthcare burden despite recent global falls in its prevalence. The risk of recurrence is high when using antibiotics such as vancomycin, particularly in already recurrent disease. In light of this, new therapy options are being perused, including novel antibiotics such as fidaxomicin, probiotics, intravenous immunoglobulin and faecal transplantation. Faecal transplantation, referred to here as human probiotic infusion (HPI), is attracting an increasing amount of interest from physicians and patients. Its use has been documented in ca. 500 cases for the treatment of CDI, with overall efficacy rates reported to be ca. 91%. The first randomised controlled trial (RCT) demonstrated that HPI was superior to a 14-day course of vancomycin (89% vs. 31%; P<0.001) and reported no deaths or serious adverse events. Safety and patient acceptability are often cited as limitations to the widespread use of this technique. However, data suggest that the short-term safety profile is encouraging, and concerns over patient acceptability are not warranted in the majority of cases. It seems appropriate to treat an infection which is caused by a major disturbance in the gut microbiota with a treatment that reverses this disturbance, rather than antibiotics that may exacerbate the problem. However, to fully understand the role of HPI in the management of CDI, further RCTs are needed with comparator antibiotics such as fidaxomicin and to establish the most efficacious HPI protocol for administration and preparation.