Current and emerging management options for Clostridium difficile infection: what is the role of fidaxomicin?

Abstract

Until recently, treatment of Clostridium difficile infection (CDI) was mainly limited to oral metronidazole and vancomycin, neither of which is optimal. Up to 25% of patients with CDI experience recurrence of infection within 30 days following treatment with these agents, while c. 45-65% of these patients experience further (and sometimes multiple) recurrences. Recurrent CDI represents a major treatment challenge for which new therapeutic options are sorely needed. Fidaxomicin is a first-in-class, oral macrocyclic antibiotic with targeted bactericidal activity against C. difficile and minimal effect on the constituents of the normal colonic microflora. This microflora-sparing activity allows for more rapid restoration of the normal colonic microflora in patients with CDI. In two separate, but almost identical, phase 3 clinical trials in which patients with CDI were treated with either fidaxomicin or vancomycin, fidaxomicin demonstrated superior clinical outcomes in comparison with the current best available treatment. While non-inferiority was demonstrated with respect to rates of clinical cure at end of treatment, significantly fewer fidaxomicin-treated patients experienced disease recurrence, which translated into clinically significant improvements in sustained clinical cure. Subsequent sub-population analyses suggest that these benefits extend to older patients, patients with severe CDI, renally impaired patients and patients with a prior episode of CDI. For CDI patients receiving concomitant antibiotics, fidaxomicin achieved significantly better rates of clinical cure and sustained clinical cure than vancomycin recipients. Fidaxomicin has a safety profile similar to oral vancomycin and appears generally well tolerated. Fidaxomicin represents an important addition to current treatment options for CDI.