• 一项3期双盲随机对照试验,182名复发性艰难梭菌感染患者分2组,在常规抗生素治疗后,服用菌群药物SER-109或安慰剂胶囊,持续3天;
  • 干预后8周内,SER-109组的复发率显著低于安慰剂组(12% vs 40%, RR 0.32),且在不同年龄段和接受不同种类抗生素的患者中均显著降低复发风险;
  • SER-109所含菌种可快速、持续地在患者中定植,且次级胆汁酸(抑制艰难梭菌孢子萌发)浓度在SER-109组更高;
  • 两组的不良事件相似,主要是轻中度胃肠道症状。
抗生素是治疗艰难梭菌感染的常规疗法,但抗生素可能破坏肠道菌群,削弱菌群对艰难梭菌的定植抵抗,易引起感染复发。New England Journal of Medicine最新发表了微生态制药公司Seres Therapeutics开发的菌群药物SER-109(从健康人类供体中纯化的厚壁菌门细菌孢子制剂)的3期临床试验结果,表明在复发性艰难梭菌感染患者中,在常规抗生素治疗后服用SER-109以促进肠道菌群重建,能有效预防艰难梭菌感染复发。

SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection



2022-01-20, Article

Abstract & Authors:展开

BACKGROUND: Current therapies for recurrent Clostridioides difficile infection do not address the disrupted microbiome, which supports C. difficile spore germination into toxin-producing bacteria. SER-109 is an investigational microbiome therapeutic composed of purified Firmicutes spores for the treatment of recurrent C. difficile infection.
METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial in which patients who had had three or more episodes of C. difficile infection (inclusive of the qualifying acute episode) received SER-109 or placebo (four capsules daily for 3 days) after standard-of-care antibiotic treatment. The primary efficacy objective was to show superiority of SER-109 as compared with placebo in reducing the risk of C. difficile infection recurrence up to 8 weeks after treatment. Diagnosis by toxin testing was performed at trial entry, and randomization was stratified according to age and antibiotic agent received. Analyses of safety, microbiome engraftment, and metabolites were also performed.
RESULTS: Among the 281 patients screened, 182 were enrolled. The percentage of patients with recurrence of C. difficile infection was 12% in the SER-109 group and 40% in the placebo group (relative risk, 0.32; 95% confidence interval [CI], 0.18 to 0.58; P<0.001 for a relative risk of <1.0; P<0.001 for a relative risk of <0.833). SER-109 led to less frequent recurrence than placebo in analyses stratified according to age stratum (relative risk, 0.24 [95% CI, 0.07 to 0.78] for patients <65 years of age and 0.36 [95% CI, 0.18 to 0.72] for those ≥65 years) and antibiotic received (relative risk, 0.41 [95% CI, 0.22 to 0.79] with vancomycin and 0.09 [95% CI, 0.01 to 0.63] with fidaxomicin). Most adverse events were mild to moderate and were gastrointestinal in nature, with similar numbers in the two groups. SER-109 dose species were detected as early as week 1 and were associated with bile-acid profiles that are known to inhibit C. difficile spore germination.
CONCLUSIONS: In patients with symptom resolution of C. difficile infection after treatment with standard-of-care antibiotics, oral administration of SER-109 was superior to placebo in reducing the risk of recurrent infection. The observed safety profile of SER-109 was similar to that of placebo. (Funded by Seres Therapeutics; ECOSPOR III number, NCT03183128. opens in new tab.)

First Authors:
Paul Feuerstadt

Correspondence Authors:
Barbara H McGovern

All Authors:
Paul Feuerstadt,Thomas J Louie,Bret Lashner,Elaine EL Wang,Liyang Diao,Jessica A Bryant,Matthew Sims,Colleen S Kraft,Stuart H Cohen,Charles S Berenson,Louis Y Korman,Christopher B Ford,Kevin D Litcofsky,Mary‑Jane Lombardo,Jennifer R Wortman,Henry Wu,John G Auniņš,Christopher WJ McChalicher,Jonathan A Winkler,Barbara H McGovern,Michele Trucksis,Matthew R Henn,Lisa von Moltke

Nature Reviews Gastroenterology and Hepatology期刊

Oral microbiome therapy efficacious for recurrent C. difficile infection