Fecal Microbiota Transplant for C. difficile Infection in Solid Organ Transplant Recipients

摘要 艰难梭菌是抗生素相关性腹泻最常见的细菌原因。实心 器官移植受者艰难梭菌感染(CDI)的比率更高，患 因免疫抑制、频繁使用抗生素和药物引起的不良后果 所有这些程序都会扰乱正常的肠道微生物区系。肠道微生物区系失调 易发生CDI，尽管接受了治疗，30%的患者仍可复发。一种新的方式来 预防CDI复发的方法是将健康人的粪便注入肠道 CDI患者，从而恢复肠道微生物区系的平衡。然而，目前还不清楚是不是 非粪便微生物移植是预防CDI复发的有效选择 在SOT收件人中。我们提出了一项随机、双盲、双模拟、安慰剂对照的研究。 在五个地点对158名SOT患者进行FMT和口服万古霉素的比较试验，至少是第一次 但CDI不超过3次复发。我们将收集受试者的粪便和血液样本 在FMT前后收集复发、CDI相关生活质量、微生物区系的数据 组成和功能。试验的主要终点是60天时间范围内的经常性CDI 在完成治疗后。次要结果是安全性和肠道微生物区系 特点。每名受试者将捐献6份粪便样本、3份血液样本和6份 去诊所就诊。每个受试者的总随访期为24周。FMT将是 使用万能捐赠者的冰冻粪便进行灌肠。通过对患者进行6次跟踪 几个月后，我们将确定FMT是否成功和安全地减少了CDI和 改善接受CDI的SOT受者的其他结局。

Abstract Clostridium difficile is the most frequent bacterial cause of antibiotic-associated diarrhea. Solid organ transplant recipients have a higher rate of C. difficile infection (CDI), and greater risk for adverse consequences because of immunosuppression, frequent antibiotic use and medical procedures all of which disrupt the normal gut microbiota. Dysbiosis of the gut microbiota predisposes to CDI which, despite treatment can recur in 30% of patients. A novel way to prevent CDI recurrence is by instilling feces from a healthy individual into the intestine of the CDI patient, thereby restoring balance in the gut microbiota. However, it is unknown whether or not fecal microbiota transplantation (FMT) is an efficacious choice for CDI recurrence prevention in SOT recipients. We propose a randomized, double-blind double-dummy placebo-controlled trial at five sites comparing FMT with oral vancomycin for 158 SOT recipients with at least a first but no more than 3 recurrences of CDI. We will collect fecal and blood samples from subjects prior to and after FMT and collect data on recurrence, CDI-related quality of life, microbiota composition and function. The trial's primary endpoint is recurrent CDI in the 60-day time frame following completion of treatment. Secondary outcomes are safety and gut microbiota characteristics. Each subject will contribute 6 stool samples, 3 blood samples and will have 6 clinic visits. Total duration of follow-up will be 24 weeks per subject. The FMT will be administered via enema using frozen stool from universal donors. By following patients for 6 months, we will determine whether FMT successfully and safely reduces recurrence of CDI and improves other outcomes in SOT recipients with CDI.