Fidaxomicin for C. difficile infections

Fidaxomicin for C. difficile infections

A new option may soon be availiable for treating Clostridia difficile infections. Fidaxomicin (not yet approved in this country) is a non-systemic (poorly absorbed) narrow spectrum macrolide antibiotic that is bacteriocidal against C. difficile infections. It recently was compared to vancomycin in a head-to-head Phase 3 noninferiority study of 629 adults. Patients with a positive stool toxin test to C. difficile were randomized to fidaxomicin 200 mg twice a day or vancomycin 125 mg four times a day. The primary endpoint was clinical cure and the secondary endpoint was recurrence within 4 weeks and global cure (no recurrence). Fidaxomicin was noninferior to vancomycin in both the intention-to-treat (88.2% cure rate with fidaxomicin vs 85.8% with vancomycin) and per-protocol analysis (92.1% and 89.8%, respectively). Significantly fewer patients had recurrence with fidaxomicin in both groups (15.4% vs 25.3%, P = 0.005 intention-to-treat, and 13.3% vs 24.0%, P = 0.004 per protocol) although the lower rate of recurrence was in the less virulent strains. For the more virulent strains, the recurrence rate was about 25% for both drugs. Fidaxomicin was associated with a higher rate of hyperuricemia and elevated transaminases (N Engl J Med 2011;364:422-431). An accompanying editorial points out that the incidence and virulence of C. difficile infections is increasing at an alarming rate in this country. Fidaxomicin inhibits vegetative forms of C. difficile while preseving intestinal flora, a combination that holds promise, and if borne out "this new agent could become a recommended therapy for C. difficile infection" (N Engl J Med 2011;364:473-475).