Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany.
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Clin Pharmacol Ther. 2021 Apr;109(4):928-941. doi: 10.1002/cpt.2202. Epub 2021 Mar 16.
Therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD) have evolved as important tools to inform rational dosing of antibiotics in individual patients with infections. In particular, critically ill patients display altered, highly variable pharmacokinetics and often suffer from infections caused by less susceptible bacteria. Consequently, TDM has been used to individualize dosing in this patient group for many years. More recently, there has been increasing research on the use of MIPD software to streamline the TDM process, which can increase the flexibility and precision of dose individualization but also requires adequate model validation and re-evaluation of existing workflows. In parallel, new minimally invasive and noninvasive technologies such as microneedle-based sensors are being developed, which-together with MIPD software-have the potential to revolutionize how patients are dosed with antibiotics. Nonetheless, carefully designed clinical trials to evaluate the benefit of TDM and MIPD approaches are still sparse, but are critically needed to justify the implementation of TDM and MIPD in clinical practice. The present review summarizes the clinical pharmacology of antibiotics, conventional TDM and MIPD approaches, and evidence of the value of TDM/MIPD for aminoglycosides, beta-lactams, glycopeptides, and linezolid, for which precision dosing approaches have been recommended.
治疗药物监测(TDM)和基于模型的精准给药(MIPD)已发展成为为感染患者个体化合理给药提供信息的重要工具。特别是危重症患者的药代动力学发生改变且高度可变,且常患有对较少敏感的细菌引起的感染。因此,多年来 TDM 已被用于为该患者群体进行个体化给药。最近,越来越多的研究关注使用 MIPD 软件来简化 TDM 过程,这可以提高剂量个体化的灵活性和精准度,但也需要充分验证模型并重新评估现有工作流程。与此同时,新的微创和非侵入性技术(如基于微针的传感器)正在开发中,这些技术与 MIPD 软件相结合,有可能彻底改变抗生素的给药方式。尽管如此,评估 TDM 和 MIPD 方法益处的精心设计的临床试验仍然很少,但对于在临床实践中证明 TDM 和 MIPD 的实施是必要的。本综述总结了抗生素的临床药理学、传统 TDM 和 MIPD 方法,以及 TDM/MIPD 对氨基糖苷类、β-内酰胺类、糖肽类和利奈唑胺的价值的证据,这些药物已被推荐采用精准给药方法。