Nuffield Department of Medicine, Oxford University, Oxford, UK.
Clin Infect Dis. 2012 Aug;55 Suppl 2(Suppl 2):S93-103. doi: 10.1093/cid/cis499.
Two recently completed phase 3 trials (003 and 004) showed fidaxomicin to be noninferior to vancomycin for curing Clostridium difficile infection (CDI) and superior for reducing CDI recurrences. In both studies, adults with active CDI were randomized to receive blinded fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times a day for 10 days. Post hoc exploratory intent-to-treat (ITT) time-to-event analyses were undertaken on the combined study 003 and 004 data, using fixed-effects meta-analysis and Cox regression models. ITT analysis of the combined 003/004 data for 1164 patients showed that fidaxomicin reduced persistent diarrhea, recurrence, or death by 40% (95% confidence interval [CI], 26%-51%; P < .0001) compared with vancomycin through day 40. A 37% (95% CI, 2%-60%; P = .037) reduction in persistent diarrhea or death was evident through day 12 (heterogeneity P = .50 vs 13-40 days), driven by 7 (1.2%) fidaxomicin versus 17 (2.9%) vancomycin deaths at <12 days. Low albumin level, low eosinophil count, and CDI treatment preenrollment were risk factors for persistent diarrhea or death at 12 days, and CDI in the previous 3 months was a risk factor for recurrence (all P < .01). Fidaxomicin has the potential to substantially improve outcomes from CDI.
两项最近完成的 3 期临床试验（003 和 004）表明， fidaxomicin 在治疗艰难梭菌感染（CDI）方面不劣于万古霉素，且在降低 CDI 复发方面优于万古霉素。在这两项研究中，患有活动性 CDI 的成年人被随机分配接受盲法 fidaxomicin 200mg，每日 2 次，或万古霉素 125mg，每日 4 次，共 10 天。对合并的 003 和 004 数据进行了事后探索性意向治疗（ITT）时间事件分析，采用固定效应荟萃分析和 Cox 回归模型。对合并的 003/004 数据中 1164 例患者的 ITT 分析表明， fidaxomicin 使持续性腹泻、复发或死亡的风险降低了 40%（95%置信区间 [CI]，26%-51%；P <.0001），与万古霉素相比，通过第 40 天。通过第 12 天（异质性 P =.50 与 13-40 天），持续性腹泻或死亡的风险降低了 37%（95%CI，2%-60%；P =.037），这是由第 12 天之前的 7 例（1.2%） fidaxomicin 与 17 例（2.9%）万古霉素死亡引起的。低白蛋白水平、低嗜酸性粒细胞计数和 CDI 治疗预登记是第 12 天持续性腹泻或死亡的危险因素，而在过去 3 个月内的 CDI 是复发的危险因素（所有 P <.01）。 fidaxomicin 有可能显著改善 CDI 的预后。
