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%À90¢0%) after one treatment. Clinical cure was 78¢2% (95% CI 67¢4%À89¢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.

In January, 2017, The Lancet Infectious Diseases published our finding 1 that Enterobacteriaceae carrying mcr-1, a plasmid-mediated colistin resistance gene, are highly heterogenous in sequence type (ST) grouping and plasmid types indicating the diversity of mcr-1-carrying bacteria in China, and mcr-1-positive Enterobacteriaceae infections were associated with male sex, immunosuppression and antibiotics use before hospitalisation. Here we report a hospital outbreak of the MCR-1-producing Klebsiella pneumoniae.Six clinical isolates including one Escherichia coli and five K pneumoniae were identified from six patients with pneumonia admitted to a paediatric leukaemia ward at a hospital in Guangzhou, China, during 2 months between December, 2015, and January, 2016. These patients were treated with different combinations of vancomycin, imipenem, lincomycin, cefotaxime, and caspofungin acetate. Two of the six patients died from their infections.All six isolates were resistant to colistin, polymyxin B, cefotaxime, and gentamicin; and the five K pneumoniae isolates were additionally resistant to ceftazidime, cefepime, amikacin, fosfomycin, and ciprofloxacin. Various resistance genes were identified by PCR and sequencing in these isolates, including mcr-1, bla TEM-1 , bla CTX-M-3 , aac(3)-IIa, aph(3')-Ia, fosA3 in E coli and mcr-1, bla TEM-1 , bla , bla CTX-M-3 , aac(3)-IVa, aphA6, armA, fosA3, qnrB4, and qnrS1 in K pneumoniae (appendix). 2All six isolates were subjected to multilocus sequence typing (MLST) and pulsed field gel electrophoresis (PFGE).1 As a result, five mcr-1-positive K pneumonia isolates were identified as ST11, and the mcr-1-positive E coli from patient 1 belonged to ST156. Results of PFGE were consistent with MLST and indicated that the five K pneumonia were clonally related. Colistin resistance was successfully transferred to E coli C6 00 with high conjugation frequencies (10 − ¹ to 10 − ²) in all isolates, suggesting that mcr-1 was located on transferable plasmids. The results of S1-PFGE and plasmid replicon typing for mcr-1-carrying plasmid in the transconjugants showed that mcr-1 was located at IncX4 plasmids of approximately 50 kb in size in all six isolates, which harboured bla TEM-1 and bla CTX-M-3 (appendix).In conclusion, we identified a hospital outbreak of an MCR-1-producing K pneumoniae ST11 strain among children with acute leukaemia. Our finding suggests that mcr-1 can spread in the hospital environment in the absence of colistin use.We declare no competing interests.

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