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

摘要 艰难梭菌是最常见的细菌性腹泻的原因。固体 器官移植受者的C.艰难梭菌感染（CDI）， 由于免疫抑制、频繁使用抗生素和医疗 所有这些都会破坏正常的肠道微生物群。肠道菌群失调 易患CDI，尽管治疗，仍有30%的患者会复发。一种新颖的方式来 预防CDI复发的方法是将健康个体的粪便滴入患者的肠道， CDI患者，从而恢复肠道微生物群的平衡。然而，目前尚不清楚是否或 非粪便微生物群移植（FMT）是预防CDI复发的有效选择 在SOT接受者中。我们提出了一个随机、双盲、双模拟、安慰剂对照 在5个研究中心进行的试验，比较了158名SOT接受者的FMT与口服万古霉素， 但CDI复发不超过3次。我们将收集受试者的粪便和血液样本 在FMT之前和之后，并收集复发、CDI相关生活质量、微生物群 组成和功能。该试验的主要终点是60天时间范围内的复发性CDI 治疗结束后。次要结果是安全性和肠道微生物群 特色每例受试者将提供6份粪便样本、3份血液样本，并将进行6次 诊所访问。每例受试者的总随访时间为24周。禁产条约将是 使用来自通用供体的冷冻粪便通过灌肠施用。通过跟踪患者6 我们将确定FMT是否成功和安全地减少CDI的复发， 改善CDI 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.