Treatment of first recurrence of Clostridium difficile infection: fidaxomicin versus vancomycin

Abstract

Recurrence of Clostridium difficile infection (CDI) occurs in approximately 25% of successfully treated patients. Two phase 3 randomized, double-blind trials were conducted at 154 sites in the United States, Canada, and Europe to compare fidaxomicin vs vancomycin in treating CDI. Patients with CDI received fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times daily for 10 days. The primary end point was clinical cure of CDI at end of treatment, and a secondary end point was recurrence during the 28 days following clinical cure. In all, 1164 subjects were enrolled, of which a subgroup of 128 in the per-protocol population had another recent episode of CDI prior to the CDI diagnosis at study enrollment. In the analysis of this subgroup, initial response to therapy was similar for both drugs (>90% cure). However, recurrence within 28 days occurred in 35.5% of patients treated with vancomycin and 19.7% of patients treated with fidaxomicin (-15.8% difference; 95% confidence interval, -30.4% to -0.3%; P = .045). Early recurrence (within 14 days) was reported in 27% of patients treated with vancomycin and 8% of patients treated with fidaxomicin (P = .003). In patients with a first recurrence of CDI, fidaxomicin was similar to vancomycin in achieving a clinical response at end of therapy but superior in preventing a second recurrence within 28 days.

Trial registration: ClinicalTrials.gov NCT00314951 NCT00468728.

Figure 1.

Disposition of patients. Patients could have >1 reason for exclusion from an analysis population. Abbreviations: BID, twice daily; CDI, Clostridium difficile infection; mITT, modified intent to treat; QID, 4 times daily.

Figure 2.

Time to recurrence by treatment group in patients with a prior episode of Clostridium difficile infection. Kaplan–Meier analysis of the probability of recurrence according to treatment group (per-protocol population). Day 0 is defined as the day the patient received the last dose of either fidaxomicin or vancomycin. The difference between treatment groups was statistically significant by both log rank (P = .02) and Wilcoxon (P = .01) tests.

Figure 3.

Time to recurrence by age group in patients with a prior episode of Clostridium difficile infection. Kaplan–Meier analysis of the probability of recurrence according to age group (per-protocol population). Day 0 is defined as the day the patient received the last dose of either fidaxomicin or vancomycin. The difference between age groups was statistically significant by both log rank (P = .006) and Wilcoxon (P = .01) tests.