A Randomized, Double-Blind, Phase 3 Safety and Efficacy Study of Ridinilazole Versus Vancomycin for Treatment of Clostridioides difficile Infection: Clinical Outcomes With Microbiome and Metabolome Correlates of Response

作者：Pablo C. Okhuysen, Mayur Ramesh, Thomas Louie, Nino Kiknadze, Julián Torre‐Cisneros, Cláudia Murta de Oliveira, Christophe Van Steenkiste, Alena Stychneuskaya, Kevin W. Garey, Julia Garcia‐Diaz, Jianling Li, Esther Duperchy, Betty Chang, Juthamas Sukbuntherng, José G. Montoya, Lori Styles, Fong Clow, Danelle F. James, Erik R. Dubberke, Mark H. Wilcox · 发表于：Clinical Infectious Diseases · 年份：2024 · DOI：10.1093/cid/ciad792 · 被引用次数：35 · 研究领域：Clostridium difficile and Clostridium perfringens research、Gut microbiota and health、Antibiotic Use and Resistance

BACKGROUND: Exposure to antibiotics predisposes to dysbiosis and Clostridioides difficile infection (CDI) that can be severe, recurrent (rCDI), and life-threatening. Nonselective drugs that treat CDI and perpetuate dysbiosis are associated with rCDI, in part due to loss of microbiome-derived secondary bile acid (SBA) production. Ridinilazole is a highly selective drug designed to treat CDI and prevent rCDI. METHODS: In this phase 3 superiority trial, adults with CDI, confirmed with a stool toxin test, were randomized to receive 10 days of ridinilazole (200 mg twice daily) or vancomycin (125 mg 4 times daily). The primary endpoint was sustained clinical response (SCR), defined as clinical response and no rCDI through 30 days after end of treatment. Secondary endpoints included rCDI and change in relative abundance of SBAs. RESULTS: Ridinilazole and vancomycin achieved an SCR rate of 73% versus 70.7%, respectively, a treatment difference of 2.2% (95% CI: -4.2%, 8.6%). Ridinilazole resulted in a 53% reduction in recurrence compared with vancomycin (8.1% vs 17.3%; 95% CI: -14.1%, -4.5%; P = .0002). Subgroup analyses revealed consistent ridinilazole benefit for reduction in rCDI across subgroups. Ridinilazole preserved microbiota diversity, increased SBAs, and did not increase the resistome. Conversely, vancomycin worsened CDI-associated dysbiosis, decreased SBAs, increased Proteobacteria abundance (∼3.5-fold), and increased the resistome. CONCLUSIONS: Although ridinilazole did no...