Pediatric Gastroenterology, Hepatology and Nutrition, Valley Children's Hospital, Madera, California, USA.
Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Cochrane Database Syst Rev. 2023 Apr 25;4(4):CD013871. doi: 10.1002/14651858.CD013871.pub2.
BACKGROUND: Clostridioides difficile (formerly known as Clostridium difficile) is a bacterium that can cause potentially life-threatening diarrheal illness in individuals with an unhealthy mixture of gut bacteria, known as dysbiosis, and can cause recurrent infections in nearly a third of infected individuals. The traditional treatment of recurrent C difficile infection (rCDI) includes antibiotics, which may further exacerbate dysbiosis. There is growing interest in correcting the underlying dysbiosis in rCDI using of fecal microbiota transplantation (FMT); and there is a need to establish the benefits and harms of FMT for the treatment of rCDI based on data from randomized controlled trials. OBJECTIVES: To evaluate the benefits and harms of donor-based fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile infection in immunocompetent people. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 31 March 2022. SELECTION CRITERIA: We considered randomized trials of adults or children with rCDI for inclusion. Eligible interventions must have met the definition of FMT, which is the administration of fecal material containing distal gut microbiota from a healthy donor to the gastrointestinal tract of a person with rCDI. The comparison group included participants who did not receive FMT and were given placebo, autologous FMT, no intervention, or antibiotics with activity against C difficile. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. proportion of participants with resolution of rCDI and 2. serious adverse events. Our secondary outcomes were 3. treatment failure, 4. all-cause mortality, 5. withdrawal from study, 6. rate of new CDI infection after a successful FMT, 7. any adverse event, 8. quality of life, and 9. colectomy. We used the GRADE criteria to assess certainty of evidence for each outcome. MAIN RESULTS: We included six studies with 320 participants. Two studies were conducted in Denmark, and one each in the Netherlands, Canada, Italy, and the US. Four were single-center and two were multicenter studies. All studies included only adults. Five studies excluded people who were severely immunocompromised, with only one study including 10 participants who were receiving immunosuppressive therapy out of the 64 enrolled; these were similarly distributed between the FMT arm (4/24 or 17%) and comparison arms (6/40 or 15%). The route of administration was the upper gastrointestinal tract via a nasoduodenal tube in one study, two studies used enema only, two used colonoscopic only delivery, and one used either nasojejunal or colonoscopic delivery, depending on a clinical determination of whether the recipient could tolerate a colonoscopy. Five studies had at least one comparison group that received vancomycin. The risk of bias (RoB 2) assessments did not find an overall high risk of bias for any outcome. All six studies assessed the efficacy and safety of FMT for the treatment of rCDI. Pooled results from six studies showed that the use of FMT in immunocompetent participants with rCDI likely leads to a large increase in resolution of rCDI in the FMT group compared to control (risk ratio (RR) 1.92, 95% confidence interval (CI) 1.36 to 2.71; P = 0.02, I = 63%; 6 studies, 320 participants; number needed to treat for an additional beneficial outcome (NNTB) 3; moderate-certainty evidence). Fecal microbiota transplantation probably results in a slight reduction in serious adverse events; however, the CIs around the summary estimate were wide (RR 0.73, 95% CI 0.38 to 1.41; P = 0.24, I² = 26%; 6 studies, 320 participants; NNTB 12; moderate-certainty evidence). Fecal microbiota transplantation may result in a reduction in all-cause mortality; however, the number of events was small, and the CIs of the summary estimate were wide (RR 0.57, 95% CI 0.22 to 1.45; P = 0.48, I = 0%; 6 studies, 320 participants; NNTB 20; low-certainty evidence). None of the included studies reported colectomy rates. AUTHORS' CONCLUSIONS: In immunocompetent adults with rCDI, FMT likely leads to a large increase in the resolution of recurrent Clostridioides difficile infection compared to alternative treatments such as antibiotics. There was no conclusive evidence regarding the safety of FMT for the treatment of rCDI as the number of events was small for serious adverse events and all-cause mortality. Additional data from large national registry databases might be required to assess any short-term or long-term risks with using FMT for the treatment of rCDI. Elimination of the single study that included some immunocompromised people did not alter these conclusions. Due to the low number of immunocompromised participants enrolled, conclusions cannot be drawn about the risks or benefits of FMT for rCDI in the immunocompromised population.
背景:艰难梭菌(以前称为艰难梭菌)是一种细菌,它会导致肠道细菌失衡(称为生态失调)的个体出现潜在危及生命的腹泻病,并可能导致近三分之一的感染个体反复感染。复发性艰难梭菌感染(rCDI)的传统治疗包括抗生素,这可能会进一步加重生态失调。越来越多的人对使用粪便微生物群移植(FMT)纠正 rCDI 中的潜在生态失调感兴趣;并且需要根据随机对照试验的数据来确定 FMT 治疗 rCDI 的益处和危害。 目的:评估供体粪便微生物群移植治疗免疫功能正常的人复发性艰难梭菌感染的益处和危害。 搜索方法:我们使用了标准的、广泛的 Cochrane 搜索方法。最新的搜索日期是 2022 年 3 月 31 日。 选择标准:我们考虑纳入患有 rCDI 的成人或儿童的随机试验。合格的干预措施必须符合 FMT 的定义,即从健康供体的远端肠道微生物群中提取粪便物质并将其施用于 rCDI 患者的胃肠道。对照组包括未接受 FMT 并接受安慰剂、自体 FMT、无干预或具有抗艰难梭菌活性的抗生素的参与者。 数据收集和分析:我们使用了标准的 Cochrane 方法。我们的主要结局是 1. rCDI 缓解的参与者比例和 2. 严重不良事件。我们的次要结局是 3. 治疗失败,4. 全因死亡率,5. 从研究中退出,6. 成功 FMT 后新 CDI 感染的发生率,7. 任何不良事件,8. 生活质量和 9. 结肠切除术。我们使用 GRADE 标准评估每个结局的证据确定性。 主要结果:我们纳入了六项研究,共 320 名参与者。两项研究在丹麦进行,一项在荷兰、加拿大、意大利和美国进行。四项为单中心研究,两项为多中心研究。所有研究均仅纳入成年人。五项研究排除了严重免疫功能低下的人群,其中只有一项研究纳入了 64 名参与者中的 10 名正在接受免疫抑制治疗;这些参与者在 FMT 组(4/24 或 17%)和对照组(6/40 或 15%)中分布相似。给药途径是上消化道,通过鼻十二指肠管,一项研究仅使用灌肠,两项研究仅使用结肠镜,一项研究根据患者是否能够耐受结肠镜检查,决定使用经鼻空肠管或结肠镜给药。五项研究均有至少一个对照组接受万古霉素。所有六项研究均评估了 FMT 治疗 rCDI 的疗效和安全性。六项研究的汇总结果表明,与对照组相比,FMT 治疗免疫功能正常的 rCDI 患者可能会大大增加 rCDI 的缓解率(RR 1.92,95%CI 1.36 至 2.71;P = 0.02,I = 63%;6 项研究,320 名参与者;需要治疗的额外获益数(NNTB)为 3;中等确定性证据)。粪便微生物群移植可能会略微降低严重不良事件的发生率;然而,汇总估计值的置信区间较宽(RR 0.73,95%CI 0.38 至 1.41;P = 0.24,I² = 26%;6 项研究,320 名参与者;NNTB 12;中等确定性证据)。粪便微生物群移植可能会降低全因死亡率;然而,事件数量较少,汇总估计值的置信区间较宽(RR 0.57,95%CI 0.22 至 1.45;P = 0.48,I = 0%;6 项研究,320 名参与者;NNTB 20;低确定性证据)。纳入的研究均未报告结肠切除术的发生率。 作者结论:在免疫功能正常的 rCDI 成人中,与替代治疗(如抗生素)相比,FMT 可能会大大增加复发性艰难梭菌感染的缓解率。由于严重不良事件和全因死亡率的事件数量较少,因此关于 FMT 治疗 rCDI 的安全性尚无确凿证据。可能需要来自大型国家登记数据库的额外数据来评估使用 FMT 治疗 rCDI 的任何短期或长期风险。消除纳入一些免疫功能低下人群的单一研究并未改变这些结论。由于纳入的免疫功能低下参与者数量较少,因此无法得出关于 FMT 治疗 rCDI 对免疫功能低下人群的风险或益处的结论。
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