Fidaxomicin versus Vancomycin for Clostridium difficile Infection
Fidaxomicin versus Vancomycin for Clostridium difficile Infection
复制标题
DOI：
10.1056/nejmoa0910812
复制
发表时间：
2011-02-03
影响因子：
158.5
通讯作者：
Shue, Youe-Kong
中科院分区：
文献类型：
--
作者：
Louie, Thomas J.;Miller, Mark A.;Shue, Youe-Kong
艰难梭菌感染是一种严重的肠道疾病，与大量的发病率和死亡率相关。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期临床试验比较了非达霉素和万古霉素治疗C。艰难梭菌感染的急性症状。艰难梭菌感染和粪便毒素试验阳性结果符合研究入组条件。我们将患者随机分配接受非达霉素（200 mg，每日两次）或万古霉素（125 mg，每日四次）口服10天。主要终点是临床治愈（症状消退，不需要进一步治疗C。在疗程结束后的第二天出现艰难梭菌感染）。次要终点为C.艰难梭菌感染（治疗后4周内腹泻和粪便毒素试验阳性结果）和总体治愈（即，共招募了629名患者，其中548名（87.1%）可以进行符合方案分析。在改良意向治疗分析（非达霉素为88.2%，万古霉素为85.8%）和符合方案分析（分别为92.1%和89.8%）中，非达霉素的临床治愈率均不劣于万古霉素。在改良意向治疗分析（15.4% vs. 25.3%，P = 0.005）和符合方案分析（13.3% vs. 24.0%，P = 0.004）中，非达霉素组感染复发的患者显著少于万古霉素组。在非北美脉冲场1型菌株患者中观察到较低的复发率。两种治疗方法的不良事件特征相似。CONCLUSIONSSThe率与非达霉素治疗后的临床治愈与万古霉素治疗后的非劣效。非达霉素与C.与非北美脉冲场1型菌株相关的艰难梭菌感染。
BACKGROUNDClostridium 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.METHODSAdults 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).RESULTSA 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.CONCLUSIONSThe 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.