Antibiotic resistance, and the emergence of pan-resistant clinical isolates, seriously threatens our capability to treat bacterial diseases, including potentially deadly hospital-acquired infections. This growing issue certainly requires multiple adequate responses, including the improvement of both diagnosis methods and use of antibacterial agents, and obviously the development of novel antibacterial drugs, especially active against Gram-negative pathogens, which represent an urgent medical need.

Considering the clinical relevance of both β-lactam antibiotics and β-lactamase-mediated resistance, the discovery and development of combinations including a β-lactamase inhibitor seems to be particularly attractive, despite being extremely challenging due to the enormous diversity, both structurally and mechanistically, of the potential β-lactamase targets. This review will cover the evolution of currently available β-lactamase inhibitors along with the most recent research leading to new β-lactamase inhibitors of potential clinical interest or already in the stage of clinical development.

抗生素耐药性和泛耐药临床分离株的出现严重威胁我们治疗细菌性疾病的能力，包括可能致命的医院获得性感染。这个不断增长的问题当然需要多种适当的应对措施，包括诊断方法的改进和抗菌剂的使用，以及显然特别是对革兰氏阴性病原体有活性的新型抗菌药物的开发，这代表了迫切的医疗需求。

考虑到β-内酰胺类抗生素和β-内酰胺酶介导的耐药性在临床上的相关性，包括β-内酰胺酶抑制剂在内的组合的发现和开发似乎特别具有吸引力，尽管由于结构和机械方面的巨大多样性而极具挑战性潜在的β-内酰胺酶靶标。这篇综述将涵盖当前可用的β-内酰胺酶抑制剂的发展，以及最新的研究，这些研究导致了具有潜在临床兴趣或已经处于临床开发阶段的新型β-内酰胺酶抑制剂。