RESUMEN
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.
RESUMEN
BACKGROUND: In 2011, 15 deep-seated Propionibacterium acnes infections were identified in patients following craniotomies in a hospital in the UK. AIM: To describe the outbreak and report findings from the investigation undertaken in order to identify the source and risk factors and inform control measures. METHODS: Data were obtained from hospital clinical records and included patient and surgical variables. Cases were defined as patients with microbiologically confirmed deep or organ space surgical site infection (SSI) caused by P. acnes following craniotomy undertaken in 2011. Four controls per case were randomly selected from patients who had a craniotomy in 2011 but who did not develop any SSI. The relationship between infection and putative exposures was examined using multivariate regression techniques. Infection prevention procedures and the theatre environment were reviewed to assess compliance with existing standards. FINDINGS: Fifteen cases and 65 controls were recruited. Odds of infection were higher for those who had a dural implant inserted during their operation [adjusted odds ratio (aOR): 14.6; 95% confidence interval (CI): 0.95-∞] and for those who had alcohol/Betadine®/chlorhexidine mix as a disinfectant (aOR: 7.9; 95% CI: 0.8-∞). Environmental investigations suggested that theatre ventilation systems delivered air exchange rates below the recommended standard. CONCLUSION: There was a positive association between using dural implants and P. acnes infection. Infection may have been facilitated by inefficient use of skin disinfectant and environmental factors. Recommendations included ongoing surveillance, the use of chlorhexidine skin disinfectant, ensuring adequate air exchanges and appropriate use of doors in theatre to minimize air turbulence.
