Clostridium difficile infection (CDI) is a significant and increasing problem, and it remains the most common cause of hospital acquired diarrhea.1 Clostridium difficile is a Gram-positive anaerobic spore-forming bacillus. It is known to be the sole cause in 20–30% of patients with antibiotic-associated diarrhea, in 50–70% of patients with antibiotic-associated colitis and in more than 90% of patients with antibiotic-associated pseudomembranous colitis. Oral metronidazole and oral vancomycin have been the primary therapeutic options in the management of CDI for the past 30 years.2
The major problem with regards to the management of CDI is recurrence of disease after the completion of treatment. Recurrence is common with both metronidazole and vancomycin, and has been reported to occur in up to 35% of cases within 30 days following treatment. With one recurrence, the rate of further CDI recurrences increases to 45–65%.2
One of the promising agents for the treatment of recurrent CDI is fidaxomicin. Fidaxomicin (Dificid®) is a macrocyclic antibiotic with a narrow spectrum of activity against gram-positive cocci.1 It was approved by the US Food and Drug Administration (FDA) in 2011 for the treatment of CDI.2 Fidaxomicin has been shown to have a comparable safety profile to vancomycin3 with potential advantages over other drugs used to treat CDI. Unlike vancomycin which is bacteriostatic, fidaxomicin is bactericidal. It has lower MICs against C. difficile when compared with vancomycin and metronidazole. In addition, fidaxomicin has a prolonged post-antibiotic effect of approximately 10 hours allowing for twice-daily dosing.2
In two large double-blind randomized Phase III trials (003 in the United States and Canada and 004 conducted at 45 sites in Europe and 41 sites in the United States and Canada), fidaxomicin was compared with vancomycin in the treatment of new onset or first recurrence of CDI. Patients received either fidaxomicin (200 mg twice daily) or vancomycin (125 mg four times daily) orally for a 10-day course of treatment. The first trial of 629 patients randomized to either fidaxomicin (n = 302) or vancomycin (n = 327) revealed no significant difference in the clinical cure rates: 88.2% for fidaxomicin and 85.8% for vancomycin. The overall recurrence rates, were lower in the fidaxomicin group at 15.4% compared to 25.3% in the vancomycin group (p= 0.005).4 The second trial also found fidaxomicin to be non-inferior with cure rates of 91.7% vs 90.6% for vancomycin.5
Most recently, a post-hoc intent to treat meta-analysis was performed on the results of the combined 003/004 Phase III trials. Of the 1164 patients included, fidaxomicin when compared to vancomycin was associated with a 40% reduction in persistent diarrhea, recurrence, or death through day 40 (95% CI: 26%-51%; p < 0.0001).6 The authors concluded that the data from these two licensing trials comparing fidaxomicin versus vancomycin suggest that this drug has the potential to substantially improve outcomes from this important healthcare-associated infection. Additional observational studies as it ...