University of Calgary, Calgary, AB, Canada.
N Engl J Med. 2011 Feb 3;364(5):422-31. doi: 10.1056/NEJMoa0910812.
Clostridium difficile infection is a serious diarrheal illness associated with substantial morbidity and mortality. Patients generally have a response to oral vancomycin or metronidazole; however, the rate of recurrence is high. This phase 3 clinical trial compared the efficacy and safety of fidaxomicin with those of vancomycin in treating C. difficile infection.
Adults with acute symptoms of C. difficile infection and a positive result on a stool toxin test were eligible for study entry. We randomly assigned patients to receive fidaxomicin (200 mg twice daily) or vancomycin (125 mg four times daily) orally for 10 days. The primary end point was clinical cure (resolution of symptoms and no need for further therapy for C. difficile infection as of the second day after the end of the course of therapy). The secondary end points were recurrence of C. difficile infection (diarrhea and a positive result on a stool toxin test within 4 weeks after treatment) and global cure (i.e., cure with no recurrence).
A total of 629 patients were enrolled, of whom 548 (87.1%) could be evaluated for the per-protocol analysis. The rates of clinical cure with fidaxomicin were noninferior to those with vancomycin in both the modified intention-to-treat analysis (88.2% with fidaxomicin and 85.8% with vancomycin) and the per-protocol analysis (92.1% and 89.8%, respectively). Significantly fewer patients in the fidaxomicin group than in the vancomycin group had a recurrence of the infection, in both the modified intention-to-treat analysis (15.4% vs. 25.3%, P=0.005) and the per-protocol analysis (13.3% vs. 24.0%, P=0.004). The lower rate of recurrence was seen in patients with non–North American Pulsed Field type 1 strains. The adverse-event profile was similar for the two therapies.
The rates of clinical cure after treatment with fidaxomicin were noninferior to those after treatment with vancomycin. Fidaxomicin was associated with a significantly lower rate of recurrence of C. difficile infection associated with non–North American Pulsed Field type 1 strains. (Funded by Optimer Pharmaceuticals; ClinicalTrials.gov number, NCT00314951.)
艰难梭菌感染是一种严重的腹泻病，与大量发病率和死亡率有关。患者通常对口服万古霉素或甲硝唑有反应；然而，复发率很高。这项 3 期临床试验比较了 fidaxomicin 与万古霉素治疗艰难梭菌感染的疗效和安全性。
有急性艰难梭菌感染症状且粪便毒素检测阳性的成年人符合研究入选标准。我们将患者随机分配接受 fidaxomicin（每日 2 次，每次 200mg）或甲硝唑（每日 4 次，每次 125mg）口服治疗 10 天。主要终点是临床治愈（治疗结束后第二天起症状缓解且无需进一步艰难梭菌感染治疗）。次要终点是艰难梭菌感染复发（治疗后 4 周内腹泻和粪便毒素检测阳性）和总体治愈（即无复发治愈）。
共纳入 629 例患者，其中 548 例（87.1%）可进行意向治疗分析。在改良意向治疗分析（fidaxomicin 组为 88.2%，万古霉素组为 85.8%）和方案分析（fidaxomicin 组为 92.1%，万古霉素组为 89.8%）中，fidaxomicin 的临床治愈率均不劣于万古霉素。在改良意向治疗分析（fidaxomicin 组为 15.4%，万古霉素组为 25.3%，P=0.005）和方案分析（fidaxomicin 组为 13.3%，万古霉素组为 24.0%，P=0.004）中，fidaxomicin 组感染复发的患者明显少于万古霉素组。这种较低的复发率见于非北美脉冲场 1 型菌株的患者。两种治疗方法的不良事件谱相似。
fidaxomicin 治疗后的临床治愈率不劣于万古霉素治疗后的临床治愈率。fidaxomicin 与非北美脉冲场 1 型菌株相关的艰难梭菌感染复发率显著降低。（由 Optimer 制药公司资助；ClinicalTrials.gov 编号，NCT00314951。）
