β-内酰胺酶抑制剂研究进展  

Research progress on β-lactamase inhibitors

作　　者：韩江雪[1] 刘忆霜[1] 肖春玲[1] Han Jiang-xue;Liu Yi-shuang;Xiao Chun-ling(Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050)

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所

出　　处：《中国抗生素杂志》2019年第6期647-653,共7页Chinese Journal of Antibiotics

基　　金：国家高技术研究发展计划(863计划)(No.2015AA020911)

摘　　要：细菌耐药问题日益严峻,已经引起了公众的广泛关注。β-内酰胺类抗生素是应用最广的抗生素,但是细菌对此类药物的耐药严重降低了药物的治疗效果,而产生β-内酰胺酶是β-内酰胺类药物耐药的主要机制,研制β-内酰胺酶抑制剂,以此作为增效剂与β-内酰胺类抗生素联用,可有效恢复细菌对β-内酰胺类药物的敏感性。临床上广泛传播的β-内酰胺酶有丝氨酸β-内酰胺酶和金属β-内酰胺酶。目前,在增效剂的研宄中,己经获得了多种有效的丝氨酸β-内酰胺酶抑制剂,许多金属β-内酰胺酶抑制剂仍处于研宄阶段。此外,为了应对由多种β-内酰胺酶引起的多重感染,研发丝氨酸β-内酰胺酶/金属β-内酰胺酶双重抑制剂也是逆转β-内酰胺类抗生素耐药性的新思路。本文综述了β-内酰胺酶抑制剂的研宄进展,为研制新型β-内酰胺酶抑制剂提供借鉴。The growing problem of bacterial resistance has caused widespread public concerns.β-Lactam antibiotics are the most widely used antibiotics, but the bacterial resistance severely reduces the therapeutic effects of drugs, and β-lactamases is the main mechanism of β-lactam resistance. The development of β-lactamase inhibitors and its use as a synergist with β-lactam antibiotics can effectively restore bacterial sensitivity to β-lactam drugs. Clinically widely disseminated β-lactamases are serine β-lactamases and metallo β-lactamases. At present, a variety of effective serine β-lactamases inhibitors have been obtained in the study of synergists, and many metallo β-lactamases inhibitors are still in the research stage. In addition, in order to cope with multiple infections of a variety of β-lactamases, the discovery of serine β-lactamases/metallo β-lactamases dual inhibitors is also a new way to reverse the resistance of β-lactam antibiotics. This article reviews the research progress of β-lactamase inhibitors and provides references for the development of novel β-lactamase inhibitors.

关 键 词：细菌耐药 Β-内酰胺酶 抑制剂 

分 类 号：R978.11[医药卫生—药品]