From Duke University Medical Center, Durham, NC (G.R.C.); Sunrise Hospital and Medical Center, Las Vegas (H.K.); Sharp Chula Vista Medical Center, Chula Vista (P.M., W.O.), and Sharp Grossmont Hospital, San Diego (J.S.O.) - both in California; MV Hospital and Research Center, Lucknow (S. Gupta), and Inamdar Multispecialty Hospital, Pune (A. Porwal) - both in India; Orlando Health, Orlando, FL (P.G.); and South Jersey Infectious Disease, Somers Point (C.L.), and the Medicines Company, Parsippany (A. Perez, S. Good, H.J., G.M.) - both in New Jersey.
N Engl J Med. 2014 Jun 5;370(23):2180-90. doi: 10.1056/NEJMoa1310422.
Oritavancin is a lipoglycopeptide with bactericidal activity against gram-positive bacteria. Its concentration-dependent activity and prolonged half-life allow for single-dose treatment.
We conducted a randomized, double-blind trial in which adults with acute bacterial skin and skin-structure infections received either a single intravenous dose of 1200 mg of oritavancin or a regimen of intravenous vancomycin twice daily for 7 to 10 days. Three efficacy end points were tested for noninferiority. The primary composite end point was defined as cessation of spreading or reduction in lesion size, absence of fever, and no need for administration of a rescue antibiotic 48 to 72 hours after administration of oritavancin. Secondary end points were clinical cure 7 to 14 days after the end of treatment, as determined by a study investigator, and a reduction in lesion size of 20% or more 48 to 72 hours after administration of oritavancin.
The modified intention-to-treat population comprised 475 patients who received oritavancin and 479 patients who received vancomycin. All three efficacy end points met the prespecified noninferiority margin of 10 percentage points for oritavancin versus vancomycin: primary end point, 82.3% versus 78.9% (95% confidence interval [CI] for the difference, -1.6 to 8.4 percentage points); investigator-assessed clinical cure, 79.6% versus 80.0% (95% CI for the difference, -5.5 to 4.7 percentage points); and proportion of patients with a reduction in lesion area of 20% or more, 86.9% versus 82.9% (95% CI for the difference, -0.5 to 8.6 percentage points). Efficacy outcomes measured according to type of pathogen, including methicillin-resistant Staphylococcus aureus, were similar in the two treatment groups. The overall frequency of adverse events was also similar, although nausea was more common among those treated with oritavancin.
A single dose of oritavancin was noninferior to twice-daily vancomycin administered for 7 to 10 days for the treatment of acute bacterial skin and skin-structure infections caused by gram-positive pathogens. (Funded by the Medicines Company; SOLO I ClinicalTrials.gov number, NCT01252719.).
奥他万星是一种具有杀菌活性的糖肽类抗生素，对革兰阳性菌具有杀菌作用。其浓度依赖性活性和较长的半衰期允许单剂量治疗。
我们进行了一项随机、双盲试验，将患有急性细菌性皮肤和皮肤结构感染的成年人分别给予单次静脉注射 1200mg 奥他万星或静脉注射万古霉素，每天 2 次，持续 7 至 10 天。我们测试了 3 个疗效终点的非劣效性。主要复合终点定义为奥他万星给药后 48 至 72 小时内停止扩散或病变缩小、无发热且无需使用挽救性抗生素。次要终点为治疗结束后 7 至 14 天时研究人员评估的临床治愈率，以及奥他万星给药后 48 至 72 小时病变面积缩小 20%或更多。
接受奥他万星和万古霉素治疗的 475 例患者和 479 例患者进入改良意向治疗人群。所有 3 个疗效终点均达到奥他万星与万古霉素相比 10 个百分点的预设非劣效性边界：主要终点，82.3%比 78.9%（差异的 95%置信区间，-1.6 至 8.4 个百分点）；研究者评估的临床治愈率，79.6%比 80.0%（差异的 95%置信区间，-5.5 至 4.7 个百分点）；病变面积缩小 20%或更多的患者比例，86.9%比 82.9%（差异的 95%置信区间，-0.5 至 8.6 个百分点）。两组治疗的病原体类型（包括耐甲氧西林金黄色葡萄球菌）的疗效结果相似。两组不良反应的总发生率也相似，虽然奥他万星组更常见恶心。
对于由革兰阳性病原体引起的急性细菌性皮肤和皮肤结构感染，单次剂量的奥他万星与连续 7 至 10 天每日 2 次给予万古霉素治疗的效果相当。（由美纳里尼公司资助；SOLO I ClinicalTrials.gov 编号，NCT01252719）。
