An investigational antibiotic developed for treating Clostridioides difficile infection (CDI) did not meet superiority for sustained clinical response (SCR) in a randomized clinical trial but significantly reduced CDI recurrence and preserved microbiome diversity compared with vancomycin, researchers reported today in Clinical Infectious Diseases.
![C diff bacteria](https://www.cidrap.umn.edu/sites/default/files/c_diff_bacteria_3.jpg)
For the trial, which was conducted at 157 sites in 26 countries, adults with CDI were randomized 1:1 to receive 10 days of ridinilazole—a narrow-spectrum antibiotic with targeted activity against C difficile—or 10 days of vancomycin. The primary endpoint was SCR, defined as clinical response and no recurrent CDI (rCDI) through 30 days after end of treatment, in the modified intention-to-treat (mITT) population. Secondary endpoints included rCDI and change in relative abundance of microbiome-derived secondary bile acids (SBAs).
53% reduction in rCDI
Ridinilazole and vancomycin achieved an SCR of 70% and 73%, respectively, for an absolute treatment difference of 2.2% (95% confidence interval [CI], –4.2% to 8.6%), which did not meet the superiority criteria. But ridinilazole resulted in a relative 53% reduction in the rCDI rate compared with vancomycin (8.1% in the ridinilazole group vs 17.3% in the vancomycin group; absolute treatment difference, –9.2%), with subgroup analyses showing a consistent benefit for ridinilazole in high-risk groups.
Ridinilazole also increased microbiome diversity and SBAs and did not increase the resistome, while vancomycin worsened CDI-associated dysbiosis, reduced SBAs, and increased the resistome. Adverse events were similar for both treatment groups (47.1% for ridinilazole vs 47.2% for vancomycin), with the majority considered mild to moderate in severity, and adverse events leading to discontinuation of the study drug were lower in the ridinilazole group (0.8%) than in the vancomycin group (2.9%).
Trial investigators say the reduction in CDI recurrence is likely related to ridinilazole's microbiome-sparing specificity, which has been demonstrated in previous studies.
"The observed reduction in rCDI is supportive of the mechanism of action of this highly selective antibiotic that has a minimal impact on the human microbiome," they wrote.