Oral, Capsulized, Frozen Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection
Oral, Capsulized, Frozen Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection
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DOI：
10.1001/jama.2014.13875
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发表时间：
2014-11-05
影响因子：
120.7
通讯作者：
Hohmann, Elizabeth L.
中科院分区：
文献类型：
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作者：
Youngster, Ilan;Russell, George H.;Hohmann, Elizabeth L.
粪便微生物群移植（FMT）已被证明对治疗复发或难治性艰难梭菌感染有效，但实际障碍和安全性问题阻碍了其广泛应用。目的评价反复难辨梭菌感染患者给予预先筛选的非亲属供者冷冻FMT胶囊后腹泻的安全性和治愈率。设计、环境和参与者开放标签、单组、初步可行性研究于2013年8月至2014年6月在波士顿麻省总医院进行。纳入了20例患者（中位年龄64.5岁，范围11-89岁），这些患者至少有3次轻度至中度艰难梭菌感染发作，6- 8周万古霉素逐渐减少治疗失败，或至少2次严重艰难梭菌感染需要住院治疗。干预措施筛选健康志愿者作为潜在的供体，制作FMT胶囊并储存在-80摄氏度（-112华氏度）。患者连续2天服用15粒胶囊，随访6个月，观察症状缓解情况和不良事件。主要结局和措施主要终点是安全性，通过2级或以上不良事件评估，以及腹泻的临床缓解，8周无复发。次要终点包括每个标准化问卷的主观幸福感和每日排便次数的改善。结果未观察到FMT引起的严重不良事件。14例患者（70%;95% CI, 47%-85%）在单胶囊FMT后腹泻得到缓解。所有6名无反应者再次接受治疗；4例腹泻缓解，导致腹泻临床缓解率总体为90% (95% CI, 68%-98%)（18/20）。每日排便次数从给药前一天的中位数5次（四分位数范围[IQR]， 3-6）减少到第3天的2次（IQR, 1-3） （P = 0.001）和8周时的1次（IQR, 1-2） （P < 0.001）。在1到10的量表上，自我排名的健康得分显著改善，从FMT前一天整体健康的中位数5分（IQR, 5-7）和胃肠道特异性健康的中位数4.5分（IQR, 3-7）到FMT给药后整体和胃肠道健康的中位数8分（IQR, 7-9） （P = .001）。需要第二次治疗以获得腹泻缓解的患者预处理健康评分较低（中位数为6.5 [IQR, 5-7.3] vs 5 [IQR, 2.8-5]; P = .02）。结论和相关性这项针对难辨梭菌复发感染患者的初步研究提供了使用无亲缘关系供者冷冻包封接种FMT后不良事件和腹泻解决率的数据。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。版权所有2014美国医学协会。版权所有。
IMPORTANCE 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.OBJECTIVE 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.INTERVENTIONS Healthy volunteers were screened as potential donors and FMT capsules were generated and stored at -80 degrees C (-112 degrees F). Patients received 15 capsules on 2 consecutive days and were followed up for symptom resolution and adverse events for up to 6 months.MAIN OUTCOMES AND MEASURES 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.RESULTS 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).CONCLUSIONS AND RELEVANCE 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. Copyright 2014 American Medical Association. All rights reserved.