From eStudySite, San Diego (W.O., J.S.O.), and AD Stats Consulting, Guerneville (A.F.D.) - both in California; First Choice Emergency Room, Austin, TX (S.G.); University Hospital for Infectious Diseases "Dr. F. Mihaljević," Zagreb, Croatia (I.P.); AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece (S.M.); Riga Stradins University, Paula Stradins Clinical Hospital, Riga, Latvia (J.G.); and Paratek Pharmaceuticals, King of Prussia, PA (L.G.-R., E.T., P.B.E., A.M., S.A.V., J.N.S., E.L.).
N Engl J Med. 2019 Feb 7;380(6):528-538. doi: 10.1056/NEJMoa1800170.
Acute bacterial skin and skin-structure infections are associated with substantial morbidity and health care costs. Omadacycline, an aminomethylcycline antibiotic that can be administered once daily either orally or intravenously, is active against pathogens that commonly cause such infections, including antibiotic-resistant strains.
In this double-blind trial, we randomly assigned adults with acute bacterial skin and skin-structure infections (in a 1:1 ratio) to receive omadacycline (100 mg given intravenously every 12 hours for two doses, then 100 mg given intravenously every 24 hours) or linezolid (600 mg given intravenously every 12 hours). A transition to oral omadacycline (300 mg every 24 hours) or oral linezolid (600 mg every 12 hours) was allowed after 3 days; the total treatment duration was 7 to 14 days. The primary end point was an early clinical response at 48 to 72 hours, defined as survival with a reduction in lesion size of at least 20% without rescue antibacterial therapy. A secondary end point was an investigator-assessed clinical response at the post-treatment evaluation 7 to 14 days after the last dose, with clinical response defined as survival with resolution or improvement in signs or symptoms of infection to the extent that further antibacterial therapy was unnecessary. For both end points, the noninferiority margin was 10 percentage points.
In the modified intention-to-treat population, omadacycline (316 patients) was noninferior to linezolid (311 patients) with respect to early clinical response (rate of response, 84.8% and 85.5%, respectively; difference, -0.7 percentage points; 95% confidence interval [CI], -6.3 to 4.9). Omadacycline also was noninferior to linezolid with respect to investigator-assessed clinical response at the post-treatment evaluation in the modified intention-to-treat population (rate of response, 86.1% and 83.6%, respectively; difference, 2.5 percentage points; 95% CI, -3.2 to 8.2) and in the clinical per-protocol population (96.3% and 93.5%, respectively; difference, 2.8 percentage points; 95% CI, -1.0 to 6.9). In both groups, the efficacy of the trial drug was similar for methicillin-susceptible and methicillin-resistant Staphylococcus aureus infections. Adverse events were reported in 48.3% of the patients in the omadacycline group and in 45.7% of those in the linezolid group; the most frequent adverse events in both groups were gastrointestinal (in 18.0% and 15.8% of the patients in the respective groups).
Omadacycline was noninferior to linezolid for the treatment of acute bacterial skin and skin-structure infections and had a similar safety profile. (Funded by Paratek Pharmaceuticals; OASIS-1 ClinicalTrials.gov number, NCT02378480 .).
急性细菌性皮肤和皮肤结构感染与较高的发病率和医疗保健费用相关。奥马环素是一种可每日一次口服或静脉内给药的氨甲基环素抗生素，对引起此类感染的常见病原体具有活性，包括具有抗药性的菌株。
在这项双盲试验中，我们以 1:1 的比例随机分配患有急性细菌性皮肤和皮肤结构感染的成年人（静脉内给予 100mg，每 12 小时一次，共 2 剂，然后每 24 小时静脉内给予 100mg）或利奈唑胺（每 12 小时静脉内给予 600mg）。在第 3 天后可以转为口服奥马环素（每 24 小时 300mg）或口服利奈唑胺（每 12 小时 600mg）；总的治疗时间为 7 至 14 天。主要终点是在 48 至 72 小时的早期临床应答，定义为无挽救性抗菌治疗时，生存且病变大小缩小至少 20%。次要终点是治疗后评估 7 至 14 天的研究者评估临床应答，临床应答定义为生存且感染的体征或症状得到缓解或改善，以致无需进一步的抗菌治疗。对于这两个终点，非劣效性边界为 10 个百分点。
在改良意向治疗人群中，奥马环素（316 例患者）在早期临床应答方面不劣于利奈唑胺（311 例患者）（应答率分别为 84.8%和 85.5%，差异为 -0.7 个百分点；95%置信区间 [CI]，-6.3 至 4.9）。在改良意向治疗人群和临床方案人群中，奥马环素也不劣于利奈唑胺的治疗后评估的研究者评估临床应答（应答率分别为 86.1%和 83.6%，差异为 2.5 个百分点；95%CI，-3.2 至 8.2）和（分别为 96.3%和 93.5%，差异为 2.8 个百分点；95%CI，-1.0 至 6.9）。在两组中，试验药物对甲氧西林敏感和耐甲氧西林金黄色葡萄球菌感染的疗效相似。奥马环素组有 48.3%的患者报告了不良事件，利奈唑胺组有 45.7%的患者报告了不良事件；两组中最常见的不良事件是胃肠道（奥马环素组和利奈唑胺组分别为 18.0%和 15.8%的患者）。
奥马环素治疗急性细菌性皮肤和皮肤结构感染不劣于利奈唑胺，且具有相似的安全性。（由 Paratek Pharmaceuticals 资助；OASIS-1 ClinicalTrials.gov 编号，NCT02378480）。
