E-study Site, Chula Vista, California.
North Estonia Medical Centre Foundation, Tallinn.
Clin Infect Dis. 2018 Aug 16;67(5):657-666. doi: 10.1093/cid/ciy165.
Delafloxacin is an intravenous (IV)/oral anionic fluoroquinolone with activity against gram-positive (including methicillin-resistant Staphylococcus aureus [MRSA]), gram-negative, atypical, and anaerobic organisms. It is approved in the United States for acute bacterial skin and skin structure infections (ABSSSIs) caused by designated susceptible gram-positive and gram-negative organisms, and is in development for the treatment of community-acquired bacterial pneumonia.
A multicenter, randomized, double-blind trial of 850 adults with ABSSSI compared delafloxacin 300 mg IV every 12 hours for 3 days with a switch to 450 mg oral delafloxacin, to vancomycin 15 mg/kg IV with aztreonam for 5-14 days. The primary endpoint was objective response at 48-72 hours. Investigator-assessed response based on resolution of signs and symptoms at follow-up (day 14 ± 1), and late follow-up (day 21-28) were secondary endpoints.
In the intent-to-treat analysis set, the objective response was 83.7% in the delafloxacin arm and 80.6% in the comparator arm. Investigator-assessed success was similar at follow-up (87.2% vs 84.4%) and late follow-up (83.5% vs 82.2%). Delafloxacin was comparable to vancomycin + aztreonam in eradication of MRSA at 96.0% vs 97.0% at follow-up. Frequency of treatment-emergent adverse events between the groups was similar. Treatment-emergent adverse events leading to study drug discontinuation was higher in the vancomycin + aztreonam group (1.2% vs 2.4%).
In ABSSSI patients, IV/oral delafloxacin monotherapy was noninferior to IV vancomycin + aztreonam combination therapy for both the objective response and the investigator-assessed response at follow-up and late follow-up. Delafloxacin was well tolerated as monotherapy in treatment of ABSSSIs.
NCT01984684.
德拉沙星是一种静脉注射（IV）/口服的阴离子氟喹诺酮类药物，对革兰阳性（包括耐甲氧西林金黄色葡萄球菌[MRSA]）、革兰阴性、非典型和厌氧生物具有活性。它在美国被批准用于治疗由指定敏感的革兰阳性和革兰阴性生物引起的急性细菌性皮肤和皮肤结构感染（ABSSSIs），并正在开发用于治疗社区获得性细菌性肺炎。
一项多中心、随机、双盲试验，纳入 850 例 ABSSSI 成人患者，比较德拉沙星 300mg IV 每 12 小时给药 3 天与转换为 450mg 口服德拉沙星，以及万古霉素 15mg/kg IV 与氨曲南 5-14 天。主要终点是 48-72 小时的客观反应。基于随访（±1 天 14 天）和晚期随访（天 21-28）时体征和症状的消退，研究者评估的反应是次要终点。
在意向治疗分析集中，德拉沙星组的客观反应率为 83.7%，对照组为 80.6%。随访时（87.2% vs 84.4%）和晚期随访时（83.5% vs 82.2%），研究者评估的成功率相似。德拉沙星与万古霉素+氨曲南在随访时对 MRSA 的清除率相当，分别为 96.0%和 97.0%。两组之间治疗中出现的不良事件的频率相似。万古霉素+氨曲南组因治疗中出现的不良事件而导致停药的发生率较高（1.2% vs 2.4%）。
在 ABSSSI 患者中，IV/口服德拉沙星单药治疗与 IV 万古霉素+氨曲南联合治疗在客观反应和随访以及晚期随访时的研究者评估反应方面均不劣效。德拉沙星作为 ABSSSIs 的单药治疗耐受性良好。
NCT01984684。
