Carbapenem resistance presents a major challenge for the global public health network, as clinical infections caused by carbapenem-resistant organisms (CRO) are frequently associated with significant morbidity and mortality. Ceftazidime–avibactam (CAZ–AVI) is a novel cephalosporin/β-lactamase inhibitor combination offering an important advance in the treatment of CRO infections. CAZ–AVI has been reported to inhibit the activities of Ambler classes A, C, and some class D enzymes. However, bacterial resistance has been emerging shortly after the introduction of this combination in clinical use, with an increasing trend. Understanding these resistance mechanisms is crucial for guiding the development of novel treatments and aiding in the prediction of underlying resistance mechanisms. This review aims to systematically summarize the epidemiology of CAZ–AVI-resistant strains and recently identified resistance mechanisms of CAZ–AVI, with a focus on the production of β-lactamase variants, the hyperexpression of β-lactamases, reduced permeability, and overexpressed efflux pumps. The various mechanisms of CAZ–AVI resistance that have emerged within a short timescale emphasize the need to optimize the use of current agents, as well as the necessity for the surveillance of CAZ–AVI-resistant pathogens.

碳青霉烯类耐药性对全球公共卫生网络构成重大挑战，因为由耐碳青霉烯类微生物 (CRO) 引起的临床感染通常与显着的发病率和死亡率相关。头孢他啶-阿维巴坦 (CAZ-AVI) 是一种新型头孢菌素/β-内酰胺酶抑制剂组合，在治疗 CRO 感染方面取得了重要进展。据报道，CAZ-AVI 可抑制 Ambler A、C 类和一些 D 类酶的活性。然而，这种组合在临床使用后不久就出现了细菌耐药性，并且呈上升趋势。了解这些耐药机制对于指导新疗法的开发和帮助预测潜在的耐药机制至关重要。本综述旨在系统总结 CAZ-AVI 耐药菌株的流行病学和最近确定的 CAZ-AVI 耐药机制，重点关注 β-内酰胺酶变体的产生、β-内酰胺酶的过度表达、通透性降低和外排过度表达泵。在短时间内出现的各种 CAZ-AVI 抗性机制强调了优化当前药物使用的必要性，以及对 CAZ-AVI 抗性病原体进行监测的必要性。