C. difficile is a significant cause of diarrhoea in hospitalised patients, particularly the elderly. The current standard of care in the UK for C. difficile-associated diarrhoea is metronidazole or vancomycin, depending on the severity of infection. However, both treatments are linked with recurrence of infection and have significant side-effects.
Fidaxomicin is a macrocyclic antibacterial which has a narrow spectrum of activity and exerts its bactericidal effect by inhibiting bacterial RNA polymerase. It has 8-fold higher activity than vancomycin against C. difficile.
"Fidaxomicin is minimally absorbed in the intestinal tract, which means it stays in the gut where C. difficile resides," says Mark Miller, Chief of the Department of Microbiology at the Jewish General Hospital in Montreal. "Fidaxomicin is also a narrow spectrum antibiotic, meaning that it acts selectively on C. difficile with minimal disruption to the healthy, protective bacteria in the gut."
Fidaxomicin was compared with vancomycin in a phase 3, double-blind, non-inferiority study published in the New England Journal of Medicine earlier this year. Investigators randomised patients (n=629) with acute symptomatic C. difficile infection to receive fidaxomicin 200mg twice daily or vancomycin 125mg four times daily for 10 days. Two days after the last dose of study drug, the researchers assessed patients for clinical cure, the primary endpoint.
The intention-to-treat analysis included 596 patients. Fidaxomicin was non-inferior to vancomycin, with similar rates of clinical cure (88.2% and 85.8%, respectively). Rates of recurrence were significantly lower with fidaxomicin than with vancomycin (15.4% vs 25.3%, p=0.005).
Similar rates of adverse effects, most commonly minor gastrointestinal symptoms such as nausea and vomiting, were observed in both treatment arms. No participant withdrew from the study as a result of intolerance or allergy.
The European Medicines Agency issued a positive opinion in September on the approval of fidaxomicin.