Ridinilazole potentially effective for C. difficile infection
The novel, targeted-spectrum antimicrobial ridinilazole showed potential in the treatment of initial Clostridium difficile (C. difficile) infection compared with vancomycin, a new study has found.
In a phase 2, double-blind trial, 100 C. difficile-positive patients were randomized to receive ridinilazole 200 mg/12 hours (n=50) or vancomycin 125 mg/6 hours for 10 days (n=50). A total of 69 patients (n=36 and 33 in the ridinilazole and vancomycin arms, respectively) were included in the modified intention-to-treat (ITT) population. [Lancet Infect Dis 2017;17:735-744]
Clinical response at test of cure in the ridinilazole and vancomycin arms had an estimated treatment difference (ETD) of 8.3 percent (90 percent confidence interval [CI], −9.3 to 25.8), translating to noninferiority of ridinilazole to vancomycin. In addition, sustained clinical response established superiority of ridinilazole over vancomycin (ETD, 21.1 percent, 90 percent CI 3.1–39.1; p=0.0004).
“The superiority of ridinilazole [over] vancomycin with regard to sustained clinical response was driven by a marked reduction in recurrent C. difficile infection, which is likely due to the highly selective activity of ridinilazole against C. difficile and the absence of collateral damage to the microbiota during therapy,” said the researchers.
On subgroup analysis, ridinilazole remained associated with more sustained clinical responses than vancomycin in patients >75 years (ETD, 42.7 percent), those with severe disease (ETD, 15.9 percent), and those with previous episodes of C. difficile infection (ETD, 19.9 percent).
“[These subgroups were evaluated as] all are at increased risk of infection and of disease recurrence following treatment,” said the researchers, adding that having faecal-toxin-positive subjects adds significance to their evaluation given the worse clinical outcomes associated with the presence of faecal toxins.
It is important to treat C. difficile infection as it entails a significant economic burden, noted the researchers. “[Furthermore, recurrence] places a substantial burden on patient welfare, is associated with increased morbidity and mortality, and is difficult to treat.”
Given the high recurrence rates associated with other antibiotics recommended for C. difficile, such as metronidazole and vancomycin, and the lack of improvement against other C. difficile strains (ie, BI/NAP1/027) with fidaxomicin, it is imperative to evaluate other drugs that could mitigate these outcomes, noted the researchers.
“[S]afe and effective alternatives that do not negatively affect the normal gut microbiota [may facilitate the] prevention of recurrent C. difficile infection … Ridinilazole has potential as a new treatment of C. difficile infection, owing to its good sustained clinical response rates … probably as a result of decreased disturbance of the normally protective intestinal microbiota,” they said.
Although the results are encouraging, the researchers called for larger studies with longer follow-up periods to further confirm the findings.