Abbanat Darren, Morrow Brian, Bush Karen
Johnson & Johnson Pharmaceutical Research and Development, L.L.C. 1000 Rte. 202, Raritan, NJ 08869, USA.
Curr Opin Pharmacol. 2008 Oct;8(5):582-92. doi: 10.1016/j.coph.2008.08.001. Epub 2008 Sep 18.
New antibacterial agents to treat infections caused by antibiotic-susceptible and antibiotic-resistant pathogens are in various stages of clinical development. In this review are compounds with demonstrated activity against methicillin-resistant staphylococci including investigational cephalosporins, carbapenems, and a new tetracycline, as well as glycopeptides effective against vancomycin-resistant enterococci (VRE), and fluoroquinolones with improved potency against respiratory pathogens and multidrug-resistant Gram-positive bacteria. Although most recent progress has occurred in the identification of agents for Gram-positive infections, broad-spectrum carbapenems are described for the treatment of multidrug-resistant Gram-negative pathogens. Also discussed are agents with mechanisms of action other than inhibition of protein synthesis, penicillin-binding proteins, and DNA topoisomerases; among these are inhibitors of bacterial fatty acid biosynthesis, peptidoglycan synthesis, and dihydrofolate reductase.
用于治疗由对抗生素敏感和耐药病原体引起的感染的新型抗菌剂正处于临床开发的不同阶段。本综述涵盖了对耐甲氧西林葡萄球菌具有已证实活性的化合物，包括研究中的头孢菌素、碳青霉烯类以及一种新型四环素，还有对万古霉素耐药肠球菌（VRE）有效的糖肽类，以及对呼吸道病原体和多重耐药革兰氏阳性菌效力增强的氟喹诺酮类。尽管最近在革兰氏阳性感染药物的鉴定方面取得了最大进展，但也描述了用于治疗多重耐药革兰氏阴性病原体的广谱碳青霉烯类。还讨论了作用机制并非抑制蛋白质合成、青霉素结合蛋白和DNA拓扑异构酶的药物；其中包括细菌脂肪酸生物合成、肽聚糖合成和二氢叶酸还原酶的抑制剂。
