Moran Gregory J, Chitra Surya, McGovern Paul C
Olive View-UCLA Medical Center, 14445 Olive View Dr, Sylmar, CA, 91342, USA.
Paratek Pharmaceuticals, Inc., King of Prussia, PA, USA.
Infect Dis Ther. 2022 Feb;11(1):517-531. doi: 10.1007/s40121-021-00587-4. Epub 2022 Jan 11.
Acute bacterial skin and skin structure infections (ABSSSI) represent one of the most common reasons for emergency department visits, and are frequent complications of intravenous drug use in persons who inject drugs (PWID). This study examined the efficacy and safety of omadacycline, versus linezolid, in PWID and persons who do not inject drugs, in the Phase 3 Omadacycline in Acute Skin and Skin Structure Infection (OASIS-1, OASIS-2) studies.
Eligible participants were aged ≥ 18 years with qualifying skin infections: wound infection, cellulitis, erysipelas, or major abscess. The primary efficacy endpoint was early clinical response (ECR) in the modified intent-to-treat (mITT) population, defined as survival with ≥ 20% reduction in lesion size at 48-72 h after the first dose of omadacycline or linezolid. Key secondary endpoints included investigator-assessed clinical response at the post-treatment evaluation (PTE) in the mITT and clinical per-protocol populations, and clinical response at PTE in the micro-mITT population. Safety was assessed based on adverse events (AEs) and standard clinical laboratory tests. Efficacy endpoints of clinical response at ECR and PTE were analyzed for the mITT and clinically evaluable (CE) PTE populations.
In total, 1380 patients (822 PWID, 558 non-PWID) were included in this secondary analysis. Wound infections were reported more frequently in the PWID subgroup (72.8%) at baseline; cellulitis or erysipelas (43.9%) and major abscess (37.4%) were the most frequently reported baseline infections in the non-PWID subgroup. Clinical success rates at ECR and PTE in the mITT population, and at PTE in the CE population, were high for patients receiving omadacycline or linezolid. Severe or serious treatment-emergent AEs (TEAEs), and TEAEs leading to discontinuation, were infrequent.
This subgroup analysis showed that omadacycline was effective and well tolerated, regardless of PWID status.
急性细菌性皮肤和皮肤结构感染（ABSSSI）是急诊就诊的最常见原因之一，也是注射吸毒者（PWID）静脉吸毒的常见并发症。本研究在急性皮肤和皮肤结构感染的奥玛环素3期研究（OASIS - 1、OASIS - 2）中，考察了奥玛环素对比利奈唑胺在注射吸毒者和非注射吸毒者中的疗效和安全性。
符合条件的参与者年龄≥18岁，患有符合条件的皮肤感染：伤口感染、蜂窝织炎、丹毒或大脓肿。主要疗效终点是改良意向性治疗（mITT）人群中的早期临床反应（ECR），定义为在首次服用奥玛环素或利奈唑胺后48 - 72小时内，病变大小减少≥20%且存活。关键次要终点包括mITT和临床符合方案人群中治疗后评估（PTE）时研究者评估的临床反应，以及微mITT人群中PTE时的临床反应。根据不良事件（AE）和标准临床实验室检查评估安全性。对mITT和临床可评估（CE）PTE人群分析了ECR和PTE时临床反应的疗效终点。
本二次分析共纳入1380例患者（822例注射吸毒者，558例非注射吸毒者）。基线时，伤口感染在注射吸毒者亚组中报告更为频繁（72.8%）；蜂窝织炎或丹毒（43.9%）和大脓肿（37.4%）是在非注射吸毒者亚组中最常报告的基线感染。接受奥玛环素或利奈唑胺的患者在mITT人群中的ECR和PTE以及CE人群中PTE的临床成功率较高。严重或导致停药的治疗中出现的不良事件（TEAE）并不常见。
该亚组分析表明，无论是否为注射吸毒者，奥玛环素均有效且耐受性良好。
