Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA, United States.
National Regional Reference Laboratory for Antimicrobial Resistance (NRL), Servicio Antimicrobianos, Instituto Nacional de Enfermedades Infecciosas, Administracion Nacional de Laboratorios e Institutos de Salud (ANLIS) "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.
Front Cell Infect Microbiol. 2022 Jul 8;12:918868. doi: 10.3389/fcimb.2022.918868. eCollection 2022.
Carbapenems are commonly used to treat infections caused by multidrug-resistant (MDR) bacteria. Unfortunately, carbapenem resistance is increasingly reported in many gram-negative bacteria, especially . Diazabicyclooctane (DBO) β-lactamase inhibitors, such as avibactam (AVI), when combined with sulbactam successfully restore sulbactam susceptibility against certain carbapenem-resistant (CRAB) isolates. In the present study, we tested zidebactam, a novel DBO with an additional mechanism of action, in combination with sulbactam against CRAB isolates, including strains that exhibited resistance against sulbactam/avibactam combination. A panel of 43 geographically and genetically distinct CRAB isolates recovered from different hospitals and containing different mechanisms of resistance were included in the present study. We also tested three reference strains (AB0057, AB5075, and AYE). Minimum inhibitory concentrations (MICs) for sulbactam (range 0.12-512 mg/l) and sulbactam plus 4 mg/l zidebactam were performed using microdilution according to CLSI Standards. A decrease ≥2 dilutions in sulbactam MICs was observed in 84% of the isolates when tested in combination with zidebactam. The sulbactam/zidebactam combination was able to restore sulbactam susceptibility in 91% of the isolates, including isolates that were resistant to sulbactam/avibactam combination. These data encouraged us to further explore sulbactam/zidebactam in other experimental models especially against CRAB isolates resistant to other DBOs.
碳青霉烯类药物通常用于治疗多重耐药（MDR）细菌引起的感染。不幸的是，许多革兰氏阴性菌中越来越多地报告出现碳青霉烯耐药性，尤其是肠杆菌科。二氮杂二环辛烷（DBO）β-内酰胺酶抑制剂，如阿维巴坦（AVI），与舒巴坦联合使用时，成功地恢复了某些耐碳青霉烯肠杆菌科（CRAB）分离株对舒巴坦的敏感性。在本研究中，我们测试了一种新型 DBO 齐他培南，它具有额外的作用机制，与舒巴坦联合用于 CRAB 分离株，包括对舒巴坦/阿维巴坦联合耐药的菌株。本研究纳入了来自不同医院的具有不同耐药机制的 43 个地理位置和遗传上不同的 CRAB 分离株。我们还测试了三个参考菌株（AB0057、AB5075 和 AYE）。根据 CLSI 标准，使用微量稀释法测定舒巴坦（范围 0.12-512 mg/L）和舒巴坦加 4 mg/L 齐他培南的最低抑菌浓度（MIC）。当与齐他培南联合检测时，84%的分离株的舒巴坦 MIC 值降低了 2 个稀释度。舒巴坦/齐他培南联合用药可使 91%的分离株恢复对舒巴坦的敏感性，包括对舒巴坦/阿维巴坦联合耐药的分离株。这些数据鼓励我们在其他实验模型中进一步探索舒巴坦/齐他培南，特别是针对对其他 DBO 耐药的 CRAB 分离株。
