The current epidemic of antibiotic resistant bacterial infections has fueled the demand for novel antibiotics exhibiting both antibacterial efficacy and anti-antibiotic resistance. This need has not been fully satisfied by the conventional “one target–one molecule” approach. Consequently, there has been rising interest in the development of multi-target antibiotics. Over the past two decades, 52% (14 out of 27) of the FDA approved antibiotics have demonstrated synergistic, multi-target mechanisms of action. Among these are three second-generation lipoglycopeptides, five new generation quinolones and six modernized β-lactams. This review focuses on the structure-activity relationship (SAR) analysis and the polypharmacological drug action of these antibiotics, to reveal how these multi-target antibiotics achieve the dual objectives of maximizing bactericidal efficacy and minimizing antibiotic resistance. The entrance of multi-target antibiotics into the FDA-approved regimens represents a milestone in the evolution of drug discovery as it has transcended from chemical library screening to rational drug design.

当前对抗生素抗性细菌感染的流行推动了对既具有抗菌功效又具有抗抗生素抗性的新型抗生素的需求。常规的“一个靶标一个分子”方法尚未完全满足这种需求。因此，人们对开发多靶标抗生素越来越感兴趣。在过去的二十年中，FDA批准的抗生素中有52％（27个中的14个）显示出协同的多目标作用机制。其中包括三个第二代脂肽，五个新一代喹诺酮和六个现代化的β-内酰胺。这篇综述着重于这些抗生素的结构-活性关系（SAR）分析和多药理药物作用，揭示这些多目标抗生素如何实现最大化杀菌效力和最小化抗生素耐药性的双重目标。由于多靶点抗生素已从化学文库筛选过渡到合理的药物设计，因此进入FDA批准的治疗方案代表着药物发现发展的一个里程碑。