Rodriguez George D, Warren Nathan, Yashayev Roman, Chitra Surya, Amodio-Groton Maria, Wright Kelly
Division of Antimicrobial Stewardship, New York-Presbyterian Queens, Flushing, NY, USA.
Columbia University School of Nursing, New York, NY, USA.
Infect Dis Ther. 2024 Dec;13(12):2637-2648. doi: 10.1007/s40121-024-01057-3. Epub 2024 Oct 26.
Appropriate oral antibiotic therapy for the treatment of acute bacterial skin and skin structure infections (ABSSSI) is a challenge, as current oral treatment guidelines do not fully cover the most common skin pathogens. Both linezolid and omadacycline are available as intravenous or bioequivalent oral formulations.
This post hoc analysis of the OASIS-1 (ClinicalTrials.gov identifier NCT02378480) and OASIS-2 (ClinicalTrials.gov identifier NCT02877927) phase 3 trials assessed safety and clinical efficacy of intravenous (IV)-start versus oral (PO)-start therapy in patients treated with omadacycline or linezolid for ABSSSI. In OASIS-1, patients were randomized to IV omadacycline or linezolid, with optional switch to oral therapy, while patients in OASIS-2 received oral omadacycline or linezolid. Treatment was provided for 7-14 days in both studies. The primary endpoint was an early clinical response (ECR) at 48 to 72 h, defined as survival and ≥ 20% reduction in lesion size, without rescue antibacterial therapy.
A total of 645 IV-start inpatients and 735 PO-start outpatients were assessed. Median age was 47 years for the IV-start group and 44 years for the PO-start group. Most patients had solely gram-positive infections (97% in each group; ECR [85.2% IV-start and 85.0% PO-start]), and the incidence of treatment-emergent adverse events (AEs) was similar between the groups. The most frequent AEs observed were nausea (11.2% [IV-start] versus 18.9% [PO-start]) and subcutaneous abscess (5.6% [IV-start] versus 1.9% [PO-start]). Discontinuation due to AEs was infrequent in both groups (2% [IV-start] versus 1.2% [PO-start]).
Oral therapy is equally efficacious to IV therapy when omadacycline or linezolid is used to treat ABSSSIs. These data strengthen the evidence for oral omadacycline as a therapeutic option for ABSSSI, particularly for patients who have experienced treatment failure because of the limitations of other therapies.
Clinicaltrials.gov, NCT02378480 and NCT02877927.
由于目前的口服治疗指南并未完全涵盖最常见的皮肤病原体，因此选择合适的口服抗生素治疗急性细菌性皮肤及皮肤结构感染（ABSSSI）颇具挑战。利奈唑胺和奥玛环素均有静脉注射剂型或生物等效的口服剂型。
本项对OASIS-1（ClinicalTrials.gov标识符NCT02378480）和OASIS-2（ClinicalTrials.gov标识符NCT02877927）这两项3期试验的事后分析，评估了奥玛环素或利奈唑胺治疗ABSSSI患者时，静脉起始治疗与口服起始治疗的安全性和临床疗效。在OASIS-1中，患者被随机分配接受静脉注射奥玛环素或利奈唑胺，并可选择转为口服治疗，而OASIS-2中的患者接受口服奥玛环素或利奈唑胺。两项研究的治疗时间均为7至14天。主要终点为48至72小时的早期临床反应（ECR），定义为存活且病变大小减少≥20%，且未接受挽救性抗菌治疗。
共评估了645例静脉起始治疗的住院患者和735例口服起始治疗的门诊患者。静脉起始治疗组的中位年龄为47岁，口服起始治疗组为44岁。大多数患者仅患有革兰氏阳性菌感染（每组97%；ECR[静脉起始治疗组为85.2%，口服起始治疗组为85.0%]），两组治疗期间出现的不良事件（AE）发生率相似。观察到的最常见AE为恶心（11.2%[静脉起始治疗组]对vs18.9%[口服起始治疗组]）和皮下脓肿（5.6%[静脉起始治疗组]对vs1.9%[口服起始治疗组]）。两组因AE停药的情况均不常见（2%[静脉起始治疗组]对vs1.2%[口服起始治疗组]）。
使用奥玛环素或利奈唑胺治疗ABSSSI时，口服治疗与静脉治疗同样有效。这些数据强化了口服奥玛环素作为ABSSSI治疗选择的证据，特别是对于因其他疗法存在局限性而治疗失败的患者。
Clinicaltrials.gov，NCT02378480和NCT02877927。
