β-内酰胺酶抑制剂复方制剂研究进展  

An update on the combinations with β-lactamase inhibitors

作　　者：宗辉 孙钰芳 陈思敏[1] 安毛毛[1] 慎慧 ZONG Hui;SUN Yu-fang;CHEN Si-min;AN Mao-mao;SHEN Hui(Department of Pharmacy,Tenth Peopled Hospital Affiliated to Tongji University 5 Shanghai 200072,China;Department of Laboratory Medicine,Tenth Peopled Hospital Affiliated to Tongji University,Shanghai 200072,China)

机构地区：[1]同济大学附属第十人民医院药学部,上海200072 [2]同济大学附属第十人民医院检验科,上海200072

出　　处：《中国新药杂志》2022年第4期343-351,共9页Chinese Journal of New Drugs

基　　金：国家自然基金面上项目(81671989);上海市科技创新计划课题(18411951302)。

摘　　要：近年来,临床上多重耐药革兰阴性菌引起感染的死亡率居高不下。β-内酰胺酶是革兰阴性菌对多种β-内酰胺类抗生素耐药的主要原因。目前,治疗耐药革兰阴性菌感染的抗菌药物研发遭遇瓶颈,21世纪以来未见基于新靶点的小分子药物上市。近年来,新药研发机构逐渐聚焦于开发β-内酰胺酶抑制剂,旨在通过克服β-内酰胺酶介导的耐药性提高现有抗菌药物的临床疗效。头孢他啶-阿维巴坦在临床上的成功应用,使β-内酰胺类抗生素/β-内酰胺酶抑制剂复方制剂成为最有望解决临床多重耐药革兰阴性菌感染的策略。本文对近年来有关β-内酰胺类抗生素/β-内酰胺酶抑制剂复方制剂的相关研究和临床应用进展进行综述,并对未来β-内酰胺酶抑制剂复方制剂的研究方向进行了展望。In recent years, the mortality rate of infection caused by multidrug-resistant Gram-negative bacteria has been staying at a high level. The production of β-lactamases is the main mechanism of gram-negative bacteria resistant to β-lactam antibiotics. The research and development of antibacterial drugs for drug-resistant gram-negative bacteria infection is currently encountering a bottleneck. Since the 21 st century, no small molecule drugs based on new targets have been marketed. In recent years, new drug research and development institutions have gradually focused on the development of inhibitors of β-lactamase, aiming to improve the clinical therapeutic effect of existing antibacterial drugs by overcoming β-lactamase-mediated resistance. The successful clinical application of ceftazidime/avibactam makes the combinations of β-lactam antibiotics/β-lactamase inhibitors the most promising strategy to solve clinical multidrug-resistant gram-negative bacteria infections. In this article, the progress in the combinations of β-lactam antibiotics and β-lactamase inhibitors in the past several years is reviewed and the future research of combinations with β-lactamase inhibitors was prospected.

关 键 词：Β-内酰胺酶 Β-内酰胺酶抑制剂 阿维巴坦 氨曲南 美罗培南 

分 类 号：R978.1[医药卫生—药品]