A Novel Microbiome Therapeutic Increases Gut Microbial Diversity and Prevents Recurrent Clostridium difficile Infection
A Novel Microbiome Therapeutic Increases Gut Microbial Diversity and Prevents Recurrent Clostridium difficile Infection
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DOI：
10.1093/infdis/jiv766
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发表时间：
2016-07-15
影响因子：
6.4
通讯作者：
Hohmann, Elizabeth L.
中科院分区：
文献类型：
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作者：
Khanna, Sahil;Pardi, Darrell S.;Hohmann, Elizabeth L.
背景复发性艰难梭菌感染（CDI）患者的复发风险≥ 60%，因为常规治疗无法解决潜在的胃肠道生态失调。本探索性研究评价了细菌孢子预防复发性CDI的安全性和有效性。方法.用乙醇处理来自健康供体的粪便标本以消除病原体。将所得孢子分级并包封用于作为SER-109口服递送。在对标准护理抗生素有反应后，队列1中的患者连续2天用SER-109治疗（几何平均剂量，1.7 x 109个孢子），队列2中的患者在1天治疗（几何平均剂量，1.1 x 108个孢子）。主要疗效终点为C缺乏。艰难梭菌阳性腹泻在8周的随访期。评估了微生物组的变化。结果30例患者（中位年龄66.5岁; 67%为女性）入组，26例（86.7%）达到主要疗效终点。3例早期自限性C.艰难梭菌阳性腹泻不需要抗生素，C.在8周时出现艰难梭菌;因此，96.7%（29/30）达到临床消退。同时，肠道微生物群迅速多样化，在SER-109处理后发现孢子的持久植入和非孢子形成细菌的生长。不良反应包括轻度腹泻、腹痛和恶心。结论. SER-109成功地预防了CDI，并具有良好的安全性，支持一种新的基于微生物组的干预作为复发性CDI的潜在疗法。
Background. Patients with recurrent Clostridium difficile infection (CDI) have a = 60% risk of relapse, as conventional therapies do not address the underlying gastrointestinal dysbiosis. This exploratory study evaluated the safety and efficacy of bacterial spores for preventing recurrent CDI. Methods. Stool specimens from healthy donors were treated with ethanol to eliminate pathogens. The resulting spores were fractionated and encapsulated for oral delivery as SER-109. Following their response to standard-of-care antibiotics, patients in cohort 1 were treated with SER-109 on 2 consecutive days (geometric mean dose, 1.7 x 109 spores), and those in cohort 2 were treated on 1 day (geometric mean dose, 1.1 x 108 spores). The primary efficacy end point was absence of C. difficile-positive diarrhea during an 8-week follow-up period. Microbiome alterations were assessed. Results. Thirty patients (median age, 66.5 years; 67% female) were enrolled, and 26 (86.7%) met the primary efficacy end point. Three patients with early, self-limiting C. difficile-positive diarrhea did not require antibiotics and tested negative for C. difficile at 8 weeks; thus, 96.7% (29 of 30) achieved clinical resolution. In parallel, gut microbiota rapidly diversified, with durable engraftment of spores and no outgrowth of non-spore-forming bacteria found after SER-109 treatment. Adverse events included mild diarrhea, abdominal pain, and nausea. Conclusions. SER-109 successfully prevented CDI and had a favorable safety profile, supporting a novel microbiome-based intervention as a potential therapy for recurrent CDI.