Division of Infectious Diseases, Massachusetts General Hospital, Boston2Harvard Medical School, Boston, Massachusetts3Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts.
Harvard Medical School, Boston, Massachusetts4Department of Gastroenterology and Nutrition, Boston Children's Hospital, Boston, Massachusetts.
JAMA. 2014 Nov 5;312(17):1772-8. doi: 10.1001/jama.2014.13875.
Fecal microbiota transplantation (FMT) has been shown to be effective in treating relapsing or refractory Clostridium difficile infection, but practical barriers and safety concerns have prevented its widespread use.
To evaluate the safety and rate of resolution of diarrhea following administration of frozen FMT capsules from prescreened unrelated donors to patients with recurrent C. difficile infection.
DESIGN, SETTING, AND PARTICIPANTS: Open-label, single-group, preliminary feasibility study conducted from August 2013 through June 2014 at Massachusetts General Hospital, Boston. Twenty patients (median age, 64.5 years; range, 11-89 years) with at least 3 episodes of mild to moderate C. difficile infection and failure of a 6- to 8-week taper with vancomycin or at least 2 episodes of severe C. difficile infection requiring hospitalization were enrolled.
Healthy volunteers were screened as potential donors and FMT capsules were generated and stored at -80°C (-112°F). Patients received 15 capsules on 2 consecutive days and were followed up for symptom resolution and adverse events for up to 6 months.
The primary end points were safety, assessed by adverse events of grade 2 or above, and clinical resolution of diarrhea with no relapse at 8 weeks. Secondary end points included improvement in subjective well-being per standardized questionnaires and daily number of bowel movements.
No serious adverse events attributed to FMT were observed. Resolution of diarrhea was achieved in 14 patients (70%; 95% CI, 47%-85%) after a single capsule-based FMT. All 6 nonresponders were re-treated; 4 had resolution of diarrhea, resulting in an overall 90% (95% CI, 68%-98%) rate of clinical resolution of diarrhea (18/20). Daily number of bowel movements decreased from a median of 5 (interquartile range [IQR], 3-6) the day prior to administration to 2 (IQR, 1-3) at day 3 (P = .001) and 1 (IQR, 1-2) at 8 weeks (P < .001). Self-ranked health scores improved significantly on a scale of 1 to 10 from a median of 5 (IQR, 5-7) for overall health and 4.5 (IQR, 3-7) for gastrointestinal-specific health on the day prior to FMT to 8 (IQR, 7-9) after FMT administration for both overall and gastrointestinal health (P = .001). Patients needing a second treatment to obtain resolution of diarrhea had lower pretreatment health scores (median, 6.5 [IQR, 5-7.3] vs 5 [IQR, 2.8-5]; P = .02).
This preliminary study among patients with relapsing C. difficile infection provides data on adverse events and rates of resolution of diarrhea following administration of FMT using frozen encapsulated inoculum from unrelated donors. Larger studies are needed to confirm these results and to evaluate long-term safety and effectiveness.
clinicaltrials.gov Identifier: NCT01914731.
粪便微生物群移植（FMT）已被证明可有效治疗复发性或难治性艰难梭菌感染，但实际障碍和安全问题阻止了其广泛应用。
评估从预先筛选的无关供体冷冻 FMT 胶囊给予患有复发性艰难梭菌感染的患者后腹泻的缓解率和安全性。
设计、地点和参与者：2013 年 8 月至 2014 年 6 月在马萨诸塞州总医院进行的开放性、单组、初步可行性研究。纳入了 20 名（中位年龄 64.5 岁；范围 11-89 岁）至少经历过 3 次轻度至中度艰难梭菌感染且万古霉素 6-8 周减量失败或至少经历过 2 次严重艰难梭菌感染需要住院的患者。
筛选健康志愿者作为潜在供体，并生成和储存 FMT 胶囊在-80°C（-112°F）。患者连续 2 天服用 15 个胶囊，并在 6 个月内跟踪症状缓解和不良反应。
主要终点是安全性，根据 2 级或以上的不良事件评估，以及 8 周内无腹泻复发的临床缓解。次要终点包括使用标准化问卷和每日排便次数评估主观幸福感的改善。
未观察到与 FMT 相关的严重不良事件。单次 FMT 后，14 名患者（70%；95%CI，47%-85%）实现了腹泻缓解。所有 6 名无反应者均接受了重新治疗；4 名患者腹泻缓解，总腹泻缓解率为 90%（95%CI，68%-98%）（18/20）。每日排便次数从治疗前的中位数 5（四分位距 [IQR]，3-6）降至第 3 天的 2（IQR，1-3）（P = .001）和第 8 周的 1（IQR，1-2）（P < .001）。自我评分健康评分在 1 到 10 分的范围内显著提高，总体健康从治疗前的中位数 5（IQR，5-7）和胃肠道特定健康的 4.5（IQR，3-7）提高到治疗后的 8（IQR，7-9）（P = .001）。需要第二次治疗以缓解腹泻的患者治疗前健康评分较低（中位数 6.5[IQR，5-7.3]与 5[IQR，2.8-5]；P = .02）。
这项在复发性艰难梭菌感染患者中的初步研究提供了关于使用来自无关供体的冷冻封装接种物进行 FMT 后不良反应和腹泻缓解率的数据。需要更大规模的研究来证实这些结果，并评估长期安全性和有效性。
clinicaltrials.gov 标识符：NCT01914731。
