Department of Pharmacy Practice, University of Illinois Chicago, Chicago, IL, USA.
Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany.
Lancet Microbe. 2022 Oct;3(10):e795-e802. doi: 10.1016/S2666-5247(22)00121-5. Epub 2022 Jun 28.
Antibiotic resistance presents an incessant threat to our drug armamentarium that necessitates novel approaches to therapy. Over the past several decades, investigation of pharmacokinetic and pharmacodynamic (PKPD) principles has substantially improved our understanding of the relationships between the antibiotic, pathogen, and infected patient. However, crucial gaps in our understanding of the pharmacology of antibacterials and their optimal use in the care of patients continue to exist; simply attaining antibiotic exposures that are considered adequate based on traditional targets can still result in treatment being unsuccessful and resistance proliferation for some infections. It is this salient paradox that points to key future directions for research in antibiotic therapeutics. This Personal View discusses six priority areas for antibiotic pharmacology research: (1) antibiotic-pathogen interactions, (2) antibiotic targets for combination therapy, (3) mechanistic models that describe the time-course of treatment response, (4) understanding and modelling of host response to infection, (5) personalised medicine through therapeutic drug management, and (6) application of these principles to support development of novel therapies. Innovative approaches that enhance our understanding of antibiotic pharmacology and facilitate more accurate predictions of treatment success, coupled with traditional pharmacology research, can be applied at the population level and to individual patients to improve outcomes.
抗生素耐药性不断威胁着我们的药物储备,这需要我们采用新的治疗方法。在过去的几十年中,对药代动力学和药效学(PKPD)原理的研究极大地提高了我们对抗生素、病原体和感染患者之间关系的理解。然而,我们对抗菌药物药理学及其在患者治疗中最佳应用的理解仍存在关键的差距;仅仅根据传统靶点获得被认为足够的抗生素暴露,仍然可能导致某些感染的治疗失败和耐药性扩散。正是这种明显的悖论,为抗生素治疗学的研究指明了未来的重点方向。本个人观点讨论了抗生素药理学研究的六个优先领域:(1)抗生素-病原体相互作用;(2)联合治疗的抗生素靶点;(3)描述治疗反应时间过程的机制模型;(4)理解和建模宿主对感染的反应;(5)通过治疗药物管理实现个体化医学;(6)应用这些原则支持新型疗法的开发。增强我们对抗生素药理学理解的创新方法,以及更准确地预测治疗成功的方法,加上传统的药理学研究,可以应用于人群和个体患者,以改善治疗效果。