Entasis Therapeutics Inc., an affiliate of Innoviva Specialty Therapeutics, Inc., Waltham, Massachusetts, USA.
Antimicrob Agents Chemother. 2024 May 2;68(5):e0169823. doi: 10.1128/aac.01698-23. Epub 2024 Apr 3.
s complex (ABC) causes severe, difficult-to-treat infections that are frequently antibiotic resistant. Sulbactam-durlobactam (SUL-DUR) is a targeted β-lactam/β-lactamase inhibitor combination antibiotic designed to treat ABC infections, including those caused by multidrug-resistant strains. In a global, pathogen-specific, randomized, controlled phase 3 trial (ATTACK), the efficacy and safety of SUL-DUR were compared to colistin, both dosed with imipenem-cilastatin as background therapy, in patients with serious infections caused by carbapenem-resistant ABC. Results from ATTACK showed that SUL-DUR met the criteria for non-inferiority to colistin for the primary efficacy endpoint of 28-day all-cause mortality with improved clinical and microbiological outcomes compared to colistin. This report describes the characterization of the baseline ABC isolates from patients enrolled in ATTACK, including an analysis of the correlation of microbiological outcomes with SUL-DUR MIC values and the molecular drivers of SUL-DUR resistance.
s 复杂 (ABC) 导致严重且难以治疗的感染,这些感染经常对抗生素产生耐药性。舒巴坦-多利巴坦 (SUL-DUR) 是一种靶向 β-内酰胺/β-内酰胺酶抑制剂联合抗生素,旨在治疗 ABC 感染,包括由多药耐药株引起的感染。在一项全球性、病原体特异性、随机、对照的 3 期试验 (ATTACK) 中,SUL-DUR 与多粘菌素的疗效和安全性进行了比较,两者均与亚胺培南-西司他丁联合作为背景治疗,用于治疗由碳青霉烯类耐药 ABC 引起的严重感染患者。ATTACK 的结果表明,SUL-DUR 在 28 天全因死亡率的主要疗效终点上不劣于多粘菌素,与多粘菌素相比,SUL-DUR 具有更好的临床和微生物学结局,达到了非劣效性标准。本报告描述了 ATTACK 入组患者基线 ABC 分离株的特征,包括对微生物学结局与 SUL-DUR MIC 值的相关性分析,以及 SUL-DUR 耐药的分子驱动因素。