Probiotic bacterial spores reduce the likelihood of C. diff relapse in the short term (NNT = 4) in frequent relapsers

Reference

Feuerstadt P, Louie TJ, Lashner B, et al. SER-109, an oral microbiome therapy for recurrent Clostridioides difficile infection. N Engl J Med 2022;386:220-229.

Synopsis

Although antibiotics like vancomycin kill toxin-producing C. difficile (CD) bacteria, they do not kill the spores, so relapses are common. SER-109 consists of live purified Firmicutes spores; Firmicutes are a type of bacteria found in the normal gut microbiome and, in theory, should inhibit the germination of CD spores. The authors identified 281 adults with at least 3 confirmed episodes of CD infection in the past 12 months who were experiencing a relapse. A total of 182 met inclusion criteria and were randomized to receive SER-109 capsules (4 capsules given once daily for 3 days). Treatment was started immediately after standard antibiotic therapy with vancomycin or fidaxomicin. The most common reason for exclusion was a negative test result for CD toxin at the time of screening. The mean age of participants was 65 years, 93% were White, and 34% in the SER-109 group and 34% in the placebo group had experienced 4 or more relapses. There was also an imbalance in the percentage of women, with more women in the SER-109 group (67% vs 53%). Analysis was by intention to treat. In the 8 weeks following treatment, CD infection recurred less often in the SER-109 group (12% vs 40%; P < .001; number needed to treat [NNT] = 4). Secondary analyses using multiple imputation for missing data and adjusting for sex and the number of previous relapses had similar results; the benefit was similar for persons younger versus older than 65 years and also did not differ by type of antibiotic. Adverse events were similar between groups. There were 3 deaths in the treatment group, due to previously diagnosed glioblastoma, an exacerbation of previously diagnosed heart failure, and a fall leading to a subdural hematoma. None were felt to be associated with the probiotic.