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[NEJM发表论文]:Omadacycline治疗社区获得性细菌性肺炎
2019年03月15日 时讯速递, 进展交流 暂无评论

Omadacycline for Community-Acquired Bacterial Pneumonia

Roman Stets, Monica Popescu, Joven R. Gonong, et al

N Engl J Med 2019; 380:517-527
DOI: 10.1056/NEJMoa1800201

Abstract

BACKGROUND 背景

Omadacycline, a new once-daily aminomethylcycline antibiotic agent that can be administered intravenously or orally, reaches high concentrations in pulmonary tissues and is active against common pathogens that cause community-acquired bacterial pneumonia.

Omadacycline是一种新的每日一剂甘酰氨环素类氨甲环素抗生素,可静脉或口服,在肺部可达到较高浓度,对于引起社区获得性细菌性肺炎的常见致病菌有效。

METHODS 方法

In a double-blind trial, we randomly assigned (in a 1:1 ratio) adults with community-acquired bacterial pneumonia (Pneumonia Severity Index risk class II, III, or IV) to receive omadacycline (100 mg intravenously every 12 hours for two doses, then 100 mg intravenously every 24 hours), or moxifloxacin (400 mg intravenously every 24 hours). A transition to oral omadacycline (300 mg every 24 hours) or moxifloxacin (400 mg every 24 hours), respectively, was allowed after 3 days; the total treatment duration was 7 to 14 days. The primary end point was early clinical response, defined as survival with improvement in at least two of four symptoms (cough, sputum production, pleuritic chest pain, and dyspnea) and no worsening of symptoms at 72 to 120 hours, without receipt of rescue antibacterial therapy. A secondary end point was investigator-assessed clinical response at a post-treatment evaluation 5 to 10 days after the last dose, with clinical response defined as resolution or improvement in signs or symptoms to the extent that further antibacterial therapy was unnecessary. A noninferiority margin of 10 percentage points was used.

在这项双盲临床试验中,我们将社区获得性细菌性肺炎成年患者(肺炎严重程度指数风险分级II、III或IV)按照1:1的比例随机分组,分别使用omadacycline(100 mg iv q12h共2剂,然后100 mg iv qd)或莫西沙星(400 mg iv qd)。治疗3天后允许分别改为口服omadacycline (300 mg qd)或莫西沙星(400 mg qd);治疗总疗程为7-14天。主要终点为早期临床反应,定义为存活且4种症状(咳嗽,咯痰,胸膜疼痛及呼吸困难)中至少2项改善,72至120小时症状没有恶化,且无需接受挽救性抗生素治疗。次要终点为治疗后评估时(最后一剂抗生素后5-10天)研究者判断的临床反应,定义为症状体征消失或改善从而无需继续抗生素治疗。采用10个百分点作为非劣效分析边界。

RESULTS 结果

The intention-to-treat population included 386 patients in the omadacycline group and 388 patients in the moxifloxacin group. Omadacycline was noninferior to moxifloxacin for early clinical response (81.1% and 82.7%, respectively; difference, −1.6 percentage points; 95% confidence interval [CI], −7.1 to 3.8), and the rates of investigator-assessed clinical response at the post-treatment evaluation were 87.6% and 85.1%, respectively (difference, 2.5 percentage points; 95% CI, −2.4 to 7.4). Adverse events that emerged after treatment initiation were reported in 41.1% of the patients in the omadacycline group and 48.5% of the patients in the moxifloxacin group; the most frequent events were gastrointestinal (10.2% and 18.0%, respectively), and the largest difference was for diarrhea (1.0% and 8.0%). Twelve deaths (8 in the omadacycline group and 4 in the moxifloxacin group) occurred during the trial.

意向治疗分析人群包括omadacycline组386名患者及莫西沙星组388名患者。omadacycline的早期临床反应不劣于莫西沙星(分别位81.1% 和 82.7%;差异,−1.6个百分点;95% 可信区间[CI], −7.1 to 3.8),治疗后评估时研究者评价临床反应分别为87.6% 和 85.1%(差异,2.5个百分点;95% CI, −2.4 to 7.4)。治疗开始后 omadacycline组41.1%的患者以及莫西沙星组48.5%的患者报告不良事件;最常见的不良事件为胃肠道(分别为10.2% 和 18.0%),差异最大的不良事件为腹泻(分别为1.0% 和 8.0%)。在试验期间共有12例患者死亡(omadacycline组8例,莫西沙星组4例)。

CONCLUSIONS 结论

Omadacycline was noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia in adults. (Funded by Paratek Pharmaceuticals; OPTIC ClinicalTrials.gov number, NCT02531438.)

Omadacycline治疗成年社区获得性细菌性肺炎患者的疗效不劣于莫西沙星。

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