粪菌移植与万古霉素治疗原发性感染的随机对照试验

Fecal Microbiota Transplantation Versus Vancomycin for Primary Infection : A Randomized Controlled Trial.

作者信息

Juul Frederik Emil, Bretthauer Michael, Johnsen Peter H, Samy Faye, Tonby Kristian, Berdal Jan Erik, Hoff Dag Arne L, Ofstad Eirik H, Abraham Awet, Seip Birgitte, Wiig Håvard, Rognstad Øyvind Bakken, Glad Ida F, Valeur Jørgen, Nissen-Lie Axel E, Ness-Jensen Eivind, Lund Kristine M A, Skjevling Linn K, Hanevik Kurt, Skudal Hilde, Melsom Ellen J, Boyar Raziye, Cooper Trond J, Ranheim Trond E, Riise Esben M, Adami Hans-Olov, Kalager Mette, Løberg Magnus, Garborg Kjetil K

机构信息

Clinical Effectiveness Research Group, Oslo University Hospital, Oslo, Norway; Clinical Effectiveness Research Group, University of Oslo, Oslo, Norway; and Vestre Viken Bærum Hospital, Gjettum, Norway (F.E.J.).

Clinical Effectiveness Research Group, Oslo University Hospital, and Clinical Effectiveness Research Group, University of Oslo, Oslo, Norway (M.B., M.K., M.L., K.K.G.).

出版信息

Ann Intern Med. 2025 Jul;178(7):940-947. doi: 10.7326/ANNALS-24-03285. Epub 2025 Jun 17.

DOI:10.7326/ANNALS-24-03285

PMID:40523286

Abstract

BACKGROUND

Fecal microbiota transplantation (FMT) is recommended for recurrent infection (CDI), but its role in primary CDI is unclear.

OBJECTIVE

To investigate the efficacy and safety of FMT in primary CDI.

DESIGN

Randomized, open-label, noninferiority, multicenter trial. (ClinicalTrials.gov: NCT03796650).

SETTING

Hospitals and primary care facilities in Norway.

PATIENTS

Adults with CDI ( toxin in stool and ≥3 loose stools daily) and no previous CDI within 365 days before enrollment.

INTERVENTION

FMT without antibiotic pretreatment versus oral vancomycin, 125 mg 4 times daily for 10 days.

MEASUREMENTS

The primary end point was clinical cure (firm stools or <3 bowel movements daily) at day 14 and no disease recurrence within 60 days with the assigned treatment alone.

RESULTS

Of 104 randomly assigned patients, 100 received FMT or the first dose of vancomycin and were eligible for analysis. Clinical cure and no disease recurrence within 60 days without additional treatment was observed in 34 of 51 patients (66.7%) with FMT versus 30 of 49 (61.2%) with vancomycin (difference, 5.4 percentage points [95.2% CI, -13.5 to 24.4 percentage points]; for noninferiority < 0.001, rejecting the hypothesis that response to FMT is 25 percentage points lower than response to vancomycin). Eleven patients in the FMT group and 4 in the vancomycin group had additional treatment. Clinical cure at day 14 and no recurrence with or without additional treatment was observed in 40 of 51 patients (78.4%) with FMT and 30 of 49 (61.2%) with vancomycin (difference, 17.2 percentage points [95.2% CI, -0.7 to 35.1 percentage points]). No significant differences in adverse events were observed between groups.

LIMITATIONS

Open-label design and reliance on clinical end points.

CONCLUSION

FMT may be considered as first-line therapy in primary CDI.

PRIMARY FUNDING SOURCE

South-East Norway Health Trust.

摘要

背景

粪便微生物群移植（FMT）被推荐用于复发性艰难梭菌感染（CDI），但其在原发性CDI中的作用尚不清楚。

目的

研究FMT治疗原发性CDI的疗效和安全性。

设计

随机、开放标签、非劣效性、多中心试验。（ClinicalTrials.gov：NCT03796650）。

地点

挪威的医院和初级保健机构。

患者

患有CDI（粪便中有毒素且每日≥3次稀便）且在入组前365天内无既往CDI病史的成年人。

干预

不进行抗生素预处理的FMT与口服万古霉素对比，口服万古霉素剂量为每日4次，每次125mg，共10天。

测量指标

主要终点为第14天时临床治愈（大便成形或每日排便<3次）且仅接受指定治疗的情况下60天内无疾病复发。

结果

104例随机分组的患者中，100例接受了FMT或第一剂万古霉素并符合分析条件。FMT组51例患者中有34例（66.7%）在第14天时临床治愈且60天内未接受额外治疗无疾病复发，万古霉素组49例中有30例（61.2%）如此（差异为5.4个百分点[95.2%CI，-13.5至24.4个百分点]；非劣效性P<0.001，拒绝FMT反应比万古霉素反应低25个百分点的假设）。FMT组有11例患者和万古霉素组有4例患者接受了额外治疗。FMT组51例患者中有40例（78.4%）无论是否接受额外治疗在第14天时临床治愈且无复发，万古霉素组49例中有30例（61.2%）如此（差异为17.2个百分点[95.2%CI，-0.7至35.1个百分点]）。两组间不良事件无显著差异。