Single-Dose Oritavancin Versus 7-10 Days of Vancomycin in the Treatment of Gram-Positive Acute Bacterial Skin and Skin Structure Infections: The SOLO II Noninferiority Study
Single-Dose Oritavancin Versus 7-10 Days of Vancomycin in the Treatment of Gram-Positive Acute Bacterial Skin and Skin Structure Infections: The SOLO II Noninferiority Study
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DOI：
10.1093/cid/ciu778
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发表时间：
2015-01-15
影响因子：
11.8
通讯作者：
O'Riordan, William
中科院分区：
文献类型：
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作者：
Corey, G. Ralph;Good, Samantha;O'Riordan, William
背景。奥利万星是一种脂糖肽抗生素，对革兰氏阳性菌具有快速杀菌活性。其浓度依赖性活性和长半衰期允许单剂量治疗。方法。在一项随机、双盲试验中，患有急性细菌性皮肤和皮肤结构感染 (ABSSSI) 的成年人接受单次静脉注射 1200 毫克剂量的奥利万星或每日两次的万古霉素 7-10 天。测试了三个疗效终点的非劣效性：(1) 48-72 小时的主要复合终点（停止扩散或病灶尺寸缩小、不发烧、不使用救援抗生素）； (2) 治疗结束后7-14天研究者评估临床治愈； (3) 48-72 小时病变面积减少 >= 20%。结果。奥利万星和万古霉素的改良意向治疗人群分别包括 503 名和 502 名患者。所有 3 个疗效终点均达到 10% 非劣效性界限：主要复合终点（80.1% vs 82.9%；95% 置信区间 [CI]，-7.5 至 2.0）、研究者评估的临床治愈率（82.7% vs 80.5%；95% CI，-2.6 至 7.0）以及病灶面积减少 >= 20% 的患者比例奥利万星与万古霉素分别为（85.9% vs 85.3%；95% CI，-3.7 至 5.0）。不同病原体（包括耐甲氧西林金黄色葡萄球菌和不良事件发生频率）的疗效结果在治疗组之间相似。结论。单次 1200 mg 剂量的奥利万星在治疗由革兰氏阳性病原体引起的 ABSSSI 方面不劣于 7-10 天的万古霉素，并且耐受性良好。奥利万星为治疗 ABSSSI 提供了多剂量疗法的单剂量替代方案。
Background. Oritavancin is a lipoglycopeptide antibiotic with rapid bactericidal activity against gram-positive bacteria. Its concentration-dependent activity and long half-life allow for single-dose treatment.Methods. In a randomized, double-blind trial, adults with acute bacterial skin and skin structure infections (ABSSSIs) received either a single intravenous 1200-mg dose of oritavancin or 7-10 days of twice-daily vancomycin. Three efficacy endpoints were tested for noninferiority: (1) primary composite endpoint at 48-72 hours (cessation of spreading or reduction in lesion size, absence of fever, and no rescue antibiotic); (2) investigator-assessed clinical cure 7-14 days after end of treatment; and (3) >= 20% reduction in lesion area at 48-72 hours.Results. A total of 503 and 502 patients comprised the modified intent-to-treat population for oritavancin and vancomycin, respectively. All 3 efficacy endpoints met the 10% noninferiority margin: the primary composite endpoint (80.1% vs 82.9%; 95% confidence interval [CI], -7.5 to 2.0), investigator-assessed clinical cure (82.7% vs 80.5%; 95% CI, -2.6 to 7.0), and proportion of patients attaining >= 20% reduction in lesion area (85.9% vs 85.3%; 95% CI, -3.7 to 5.0) for oritavancin vs vancomycin, respectively. Efficacy outcomes by pathogen, including methicillin-resistant Staphylococcus aureus and the frequency of adverse events, were similar between treatment groups.Conclusions. A single 1200-mg dose of oritavancin was noninferior to 7-10 days of vancomycin in treating ABSSSIs caused by gram-positive pathogens, and was well tolerated. Oritavancin provides a single-dose alternative to multidose therapies for the treatment of ABSSSIs.