From City Clinical Hospital #6, Zaporizhzhia, Ukraine (R.S.); Sf. Pantelimon Clinical Emergency Hospital, Bucharest, Romania (M.P.); Lung Center of the Philippines, Manila (J.R.G.); Lakeview Hospital, Benoni, South Africa (I.M.); EMMS, Nazareth Hospital, Nazareth, and Faculty of Medicine in the Galilee, Bar-Ilan University, Safed - both in Israel (W.N.); the Department of Internal Medicine and Pharmacology, Andrzej Frycz Modrzewski Krakow University, Krakow, Poland (A. Madej); AD Stats Consulting, Guerneville, CA (A.F.D.); and Paratek Pharmaceuticals, King of Prussia, PA (C.K., L.G.-R., J.N.S., A. Manley, P.B.E., E.T., P.C.M., E.L.).
N Engl J Med. 2019 Feb 7;380(6):517-527. doi: 10.1056/NEJMoa1800201.
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.
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.
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.
Omadacycline was noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia in adults. (Funded by Paratek Pharmaceuticals; OPTIC ClinicalTrials.gov number, NCT02531438 .).
奥马环素是一种新型的每日一次的氨甲基环素类抗生素，可静脉注射或口服给药，在肺部组织中达到高浓度，对引起社区获得性细菌性肺炎的常见病原体具有活性。
在一项双盲试验中，我们将患有社区获得性细菌性肺炎（肺炎严重指数风险类别 II、III 或 IV）的成年人随机分为（1:1 比例）接受奥马环素（100 mg 静脉注射，每 12 小时一次，共 2 剂，然后每 24 小时静脉注射 100 mg）或莫西沙星（400 mg 静脉注射，每 24 小时一次）。允许在第 3 天后分别转为口服奥马环素（300 mg 每 24 小时一次）或莫西沙星（400 mg 每 24 小时一次），总治疗时间为 7 至 14 天。主要终点是早期临床反应，定义为在 72 至 120 小时内没有改善症状且无恶化的情况下，至少有咳嗽、咳痰、胸膜炎胸痛和呼吸困难 4 种症状中的 2 种症状改善的生存，无需接受挽救性抗菌治疗。次要终点是在最后一次给药后 5 至 10 天进行治疗后评估时，研究者评估的临床反应，临床反应定义为体征或症状改善或消退到无需进一步抗菌治疗的程度。使用 10 个百分点的非劣效性边界。
意向治疗人群包括奥马环素组 386 例和莫西沙星组 388 例患者。奥马环素在早期临床反应方面不劣于莫西沙星（分别为 81.1%和 82.7%；差异为-1.6 个百分点；95%置信区间 [CI]，-7.1 至 3.8），治疗后评估的研究者评估临床反应率分别为 87.6%和 85.1%（差异为 2.5 个百分点；95%CI，-2.4 至 7.4）。奥马环素组和莫西沙星组分别有 41.1%和 48.5%的患者出现治疗开始后出现的不良事件；最常见的事件是胃肠道（分别为 10.2%和 18.0%），最大的差异是腹泻（1.0%和 8.0%）。在试验期间，有 12 例死亡（奥马环素组 8 例，莫西沙星组 4 例）。
奥马环素在治疗成人社区获得性细菌性肺炎方面不劣于莫西沙星。（由 Paratek 制药公司资助；OPTI C 临床试验.gov 编号，NCT02531438）。
