Results from the first English stool bank using faecal microbiota transplant as a medicinal product for the treatment of Clostridioides difficile infection
Results from the first English stool bank using faecal microbiota transplant as a medicinal product for the treatment of Clostridioides difficile infection
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DOI：
10.1016/j.eclinm.2020.100301
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发表时间：
2020-03-01
影响因子：
15.1
通讯作者：
Hawkey, P. M.
中科院分区：
文献类型：
--
作者：
McCune, V. L.;Quraishi, M. N.;Hawkey, P. M.
背景：与抗生素治疗相比，粪便微生物群移植（FMT）治疗艰难梭菌感染（CDI）的效果有所改善。与美国和加拿大类似，FMT在英国被归类为医药产品，在没有适当许可的情况下，通过粪便库限制供应。在迄今为止最大的英国队列研究中，我们描述了124名接受FMT治疗复发性或难治性CDI患者的临床结果，并提出了将FMT作为许可药品生产的框架。方法：匿名无血缘关系的健康献血者，通过健康评估和微生物检测对捐献的粪便进行筛选。在有氧条件下，按照符合良好生产规范的生产框架，制备FMT等分液供立即使用或冷冻储存。结局指标是FMT的临床反应，定义为7天内腹泻消退，临床治愈定义为90天内无腹泻复发。结果：一次治疗后临床缓解率为83.9% （95% CI 76.0% ~ 90.0%）。整个队列的临床治愈率为78.2% （95% CI 67.4%-89.0%）。与复发病例相比，难治性病例似乎具有较低的初始临床缓解率，但在第90天，两组之间没有观察到差异。解释：这里开发的方法使FMT成功获得药品和保健产品监管机构作为药品的许可。这扩大了通过粪便库在国民保健服务中提供FMT的范围，并可在世界各地的其他中心应用，以改善获得安全和有质量保证的治疗的机会。(C) 2020由Elsevier Ltd.出版。这是一篇基于CC BY-NC-ND许可的开放获取文章。(http://creativecommons.org/licenses/by-nc-nd/4.0/)
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. (C) 2020 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)