Ridinilazole: a novel, narrow-spectrum antimicrobial agent targeting Clostridium (Clostridioides) difficile

Abstract

Clostridium (Clostridioides) difficile infection (CDI) remains an urgent threat to patients in health systems worldwide. Recurrent CDI occurs in up to 30% of cases due to sustained dysbiosis of the gut microbiota which normally protects against CDI. Associated costs of initial and recurrent episodes of CDI impose heavy financial burdens on health systems. Vancomycin and metronidazole have been the mainstay of therapy for CDI for many years; however, these agents continue to cause significant disruption to the gut microbiota and thus carry a high risk of recurrence for CDI patients. Treatment regimens are now turning towards novel narrow spectrum antimicrobial agents which target C. difficile while conserving the commensal gut microbiota, thus significantly reducing risk of recurrence. One such agent, fidaxomicin, has been in therapeutic use for several years and is now recommended as a first-line treatment for CDI, as it is superior to vancomycin in reducing risk of recurrence. Another narrow spectrum agent, ridnilazole, was recently developed and is undergoing evaluation of its potential clinical utility. This review aimed to summarize experimental reports of ridinilazole and assess its potential as a first-line agent for treatment of CDI. Reported results from in vitro assessments, and from hamster models of CDI, show potent activity against C. difficile, non-inferiority to vancomycin for clinical cure and non-susceptibility among most gut commensal bacteria. Phase I and II clinical trials have been completed with ridinilazole showing high tolerability and efficacy in treatment of CDI, and superiority over vancomycin in reducing recurrence of CDI within 30 days of treatment completion. Phase III trials are currently underway, the results of which may prove its potential to reduce recurrent CDI and lessen the heavy health and financial burden C. difficile imposes on patients and healthcare systems.

What are the missing pieces needed to stop antibiotic resistance?

“…This feature has not explored in detail because most efforts in the field have gone to broad spectrum antibiotics. Narrow spectrum antimicrobials (Collins & Riley, 2022 ) inhibiting species‐specific targets might be useful for reducing their general impact on the microbiome as long as fast methods for the identification of the agent causing the infection are developed (see below).…”

From signal transduction to protein toxins—a narrative review about milestones on the research route of C. difficile toxins

“…What are further developments? Another narrow spectrum agent, ridinilazole, is presently studied in clinical trials (Collins and Riley 2022 ). The molecular mechanism of this compound is different, as it appears to inhibit septum formation of clostridia and to impair cell division of C. difficile (Basseres et al 2016 ).…”