Otsuka Yasunari
Institute of Microbial Chemistry (BIKAKEN), Numazu.
Chem Pharm Bull (Tokyo). 2020;68(3):182-190. doi: 10.1248/cpb.c19-00842.
The emergence of multidrug-resistant (MDR) Gram-negative bacteria has become a global problem. Among MDR Gram-negative bacteria, carbapenem-resistant Enterobacteriaceae (CRE), MDR Pseudomonas aeruginosa, and MDR Acinetobacter baumannii have limited treatment options and present serious threats. Therefore, strong countermeasures must be taken against these bacteria immediately. Accordingly, the focus of this review is on recent advances in the development of promising antibacterial agents against MDR Gram-negative bacteria. These agents include novel tetracyclines, polymyxins, β-lactams, β-lactam/β-lactamase inhibitors, aminoglycosides, and peptide mimetics that have been recently approved or have shown promising results in clinical and preclinical development. This review summarizes these potent antibiotics in terms of their development status, mode of action, spectra of activity, and structure-activity relationship.
多重耐药革兰氏阴性菌的出现已成为一个全球性问题。在多重耐药革兰氏阴性菌中,耐碳青霉烯类肠杆菌科细菌(CRE)、多重耐药铜绿假单胞菌和多重耐药鲍曼不动杆菌的治疗选择有限,并构成严重威胁。因此,必须立即针对这些细菌采取强有力的对策。相应地,本综述的重点是针对多重耐药革兰氏阴性菌开发有前景的抗菌剂的最新进展。这些药物包括新型四环素类、多粘菌素类、β-内酰胺类、β-内酰胺/β-内酰胺酶抑制剂、氨基糖苷类以及在临床和临床前开发中最近已获批准或显示出有前景结果的肽模拟物。本综述根据这些强效抗生素的开发状态、作用方式、活性谱和构效关系对其进行了总结。