Zhong P, Shortridge V
Abbott Laboratories, Abbott Park, IL 60064, USA.
Curr Drug Targets Infect Disord. 2001 Aug;1(2):125-31. doi: 10.2174/1568005014606071.
The bacterial ribosome is a target for a variety of drug classes including macrolides. Macrolide antibiotics are primarily used for the treatment of respiratory tract infections. One of the most important features of the macrolide class is the excellent safety profile allowing the drug to be used broadly across all age groups. The emergence of macrolide resistance, especially in S. pneumoniae, threatens the long-term usefulness of macrolide antibiotics. The newly developed ketolide class, including telithromycin and ABT-773, evolved from the macrolide class and displays significant improvements over macrolides while maintaining safety profiles similar to macrolides. The key improvement in antimicrobial spectrum is the in vitro potency against macrolide resistant pathogens, especially S. pneumoniae. This review outlines the key improvements of ketolides over macrolides in terms of in vitro microbiology, as well as the pharmacokinetic and pharmacodynamic profiles and updates the current understanding of drug-ribosome interactions. The application of cutting-edge technology such as ribosome structure-based rational drug design and genetic engineering are also briefly discussed.
细菌核糖体是包括大环内酯类在内的多种药物的作用靶点。大环内酯类抗生素主要用于治疗呼吸道感染。大环内酯类药物最重要的特点之一是安全性极佳，使得该药物可广泛应用于所有年龄组。大环内酯类耐药性的出现，尤其是肺炎链球菌中的耐药性，威胁着大环内酯类抗生素的长期有效性。新开发的酮内酯类药物，包括泰利霉素和ABT - 773，由大环内酯类药物衍生而来，在保持与大环内酯类相似安全性的同时，相较于大环内酯类有显著改进。抗菌谱的关键改进在于对大环内酯类耐药病原体，尤其是肺炎链球菌的体外抗菌效力。本综述概述了酮内酯类在体外微生物学方面相对于大环内酯类的关键改进，以及药代动力学和药效学特征，并更新了目前对药物 - 核糖体相互作用的认识。还简要讨论了基于核糖体结构的合理药物设计和基因工程等前沿技术的应用。
