头孢洛扎他唑巴坦与左氧氟沙星治疗包括肾盂肾炎在内的复杂性尿路感染的随机、双盲、3 期试验（ASPECT-cUTI）。

Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI).

机构信息

Clinic for Urology, Paediatric Urology and Andrology, Justus-Liebig University, Giessen, Germany.

Cubist Pharmaceuticals, Lexington, MA, USA.

出版信息

Lancet. 2015 May 16;385(9981):1949-56. doi: 10.1016/S0140-6736(14)62220-0. Epub 2015 Apr 27.

DOI:10.1016/S0140-6736(14)62220-0

PMID:25931244

Abstract

BACKGROUND

Treatment of complicated urinary-tract infections is challenging due to rising antimicrobial resistance. We assessed the efficacy and safety of ceftolozane-tazobactam, a novel antibacterial with Gram-negative activity, in the treatment of patients with complicated lower-urinary-tract infections or pyelonephritis.

METHODS

ASPECT-cUTI was a randomised, double-blind, double-dummy, non-inferiority trial done in 209 centres in 25 countries. Between July, 2011, and September, 2013, hospital inpatients aged 18 years or older who had pyuria and a diagnosis of a complicated lower-urinary-tract infection or pyelonephritis were randomly assigned in a 1:1 ratio to receive intravenous 1·5 g ceftolozane-tazobactam every 8 h or intravenous high-dose (750 mg) levofloxacin once daily for 7 days. The randomisation schedule was computer generated in blocks of four and stratified by study site. The next allocation was obtained by the study site pharmacist via an interactive voice-response system. The primary endpoint was a composite of microbiological eradication and clinical cure 5-9 days after treatment in the microbiological modified intention-to-treat (MITT) population, with a non-inferiority margin of 10%. This study is registered with ClinicalTrials.gov, numbers NCT01345929 and NCT01345955.

FINDINGS

Of 1083 patients enrolled, 800 (73·9%), of whom 656 (82·0%) had pyelonephritis, were included in the microbiological MITT population. Ceftolozane-tazobactam was non-inferior to levofloxacin for composite cure (306 [76·9%] of 398 vs 275 [68·4%] of 402, 95% CI 2·3-14·6) and, as the lower bound of the two-sided 95% CI around the treatment difference was positive and greater than zero, superiority was indicated. Adverse event profiles were similar in the two treatment groups and were mainly non-serious.

INTERPRETATION

Treatment with ceftolozane-tazobactam led to better responses than high-dose levofloxacin in patients with complicated lower-urinary-tract infections or pyelonephritis.

FUNDING

Cubist Pharmaceuticals.

摘要

背景

由于抗菌药物耐药性的上升，治疗复杂尿路感染具有挑战性。我们评估了新型革兰氏阴性活性抗菌药物头孢洛扎他唑巴坦治疗复杂性下尿路感染或肾盂肾炎患者的疗效和安全性。

方法

ASPECT-cUTI 是一项在 25 个国家的 209 个中心进行的随机、双盲、双模拟、非劣效性试验。2011 年 7 月至 2013 年 9 月，年龄 18 岁或以上的住院患者，有脓尿且诊断为复杂下尿路感染或肾盂肾炎，按 1:1 比例随机分配，接受静脉注射 1.5g 头孢洛扎他唑巴坦，每 8 小时一次，或静脉注射高剂量（750mg）左氧氟沙星，每日一次，疗程 7 天。随机分组方案以 4 为一组，以研究地点分层。通过交互式语音应答系统，由研究地点药剂师获取下一个分组。主要终点为微生物改良意向治疗（MITT）人群中治疗后 5-9 天的微生物学清除和临床治愈率的复合指标，非劣效性边界为 10%。这项研究在 ClinicalTrials.gov 注册，编号为 NCT01345929 和 NCT01345955。

结果

在纳入的 1083 例患者中，800 例（73.9%），其中 656 例（82.0%）患有肾盂肾炎，被纳入微生物学 MITT 人群。头孢洛扎他唑巴坦治疗的复合治愈率不劣于左氧氟沙星（306[76.9%]例 398 例 vs 275[68.4%]例 402 例，95%CI 2.3-14.6），并且由于治疗差异的双侧 95%CI 的下限为正且大于零，表明存在优越性。两组的不良事件谱相似，主要为非严重事件。