Antimicrobial profile and clinical evidence of fidaxomicin (Dafclir®), a therapeutic agent for clostridioides (clostridium) difficile infection

Abstract

Fidaxomicin (Dafclir® Tablets 200 mg) is a member of a novel class of oral, 18-membered macrocyclic antibiotic agents used for the treatment of patients with Clostridioides (Clostridium) difficile (C. difficile) infection (CDI), approved in Japan in July 2018. Preclinical studies demonstrated that fidaxomicin inhibits RNA synthesis by bacterial DNA-dependent RNA polymerase derived from C. difficile, shows antibacterial activities against C. difficile clinically isolated in Japan, and is bactericidal against C. difficile. Fidaxomicin was less likely to disrupt gut microflora due to its narrow antimicrobial spectrum, showing antibacterial activities against limited gram-positive bacteria including C. difficile, but not against gram-negative bacteria, as determined by minimum inhibitory concentration (MIC) measurement against American Type Culture Collection strains. Fidaxomicin inhibited spore production, subsequent spore recovery/ outgrowth after removal of fidaxomicin, outgrowth to vegetative cells, and toxin production under fidaxomicin at lower MIC. Additionally, it had protective effects on lethal CDI in animal models. In clinical studies conducted in Europe, US, and Japan, fidaxomicin 200 mg twice daily for 10 days showed higher clinical cure, higher global cure (cure with no recurrence), and lower recurrence rate compared with oral vancomycin 125 mg four times daily for 10 days. Adverse events observed in the fidaxomicin group were similar to those in the vancomycin group, and no clinically important findings regarding safety and tolerability were reported. In conclusion, in vitro, in vivo and clinical evidence indicate that fidaxomicin is an effective treatment for C. difficile, with limited disruption to gut microflora, for adult patients with CDI in Japan.