University of Queensland Centre for Clinical Research, Faculty of Medicine, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, Queensland, Australia.
Pharmacy Department, Sunshine Coast University Hospital, Birtinya, Queensland, Australia.
Semin Respir Crit Care Med. 2019 Aug;40(4):476-487. doi: 10.1055/s-0039-1693498. Epub 2019 Oct 4.
Despite therapeutic advances over recent decades, the mortality rate for sepsis and septic shock is still approximately 25% worldwide. Early administration of appropriate intravenous antibiotics in the right dose is one of the cornerstones of treatment of sepsis. β-Lactam antibiotics are the most commonly prescribed in critically ill patients, and dosages that do not achieve specific pharmacokinetic/pharmacodynamic targets may increase the likelihood of treatment failure and even emergence of antibiotic resistance. Fluctuations in physiological parameters are often observed in critically ill patients, leading to altered pharmacokinetics and increased risk of suboptimal exposures, especially if standard dosing according to the product information is prescribed. Contemporary evidence illustrates that therapeutic β-lactam concentrations are inconsistently achieved at steady state. This review will investigate alternative β-lactam dose optimization strategies including prolonged infusions, guideline-based dosing, therapeutic drug monitoring (TDM), and the use of dose optimization software, all of which aim to increase the likelihood of achieving therapeutic drug concentrations and improve clinical outcomes as compared with the standard dosing approach. These dose optimization strategies have been the subject of a growing body of evidence; however, further investigation into the outcome benefits and validity of both non-TDM and TDM dosing strategies is required. For the clinician, it is important to select a feasible dosing strategy tailored for the individual patient, which will maximize the likelihood of achieving therapeutic concentrations at steady state and maintain these exposures throughout the course of therapy.
尽管近几十年来治疗方法有所进步，但全球脓毒症和感染性休克的死亡率仍约为 25%。早期给予适当剂量的静脉内抗生素是治疗脓毒症的基石之一。在重症患者中，最常开的β-内酰胺类抗生素，如果剂量不能达到特定的药代动力学/药效学目标，可能会增加治疗失败的可能性，甚至出现抗生素耐药性。重症患者经常观察到生理参数的波动，导致药代动力学改变和暴露不足的风险增加，尤其是如果根据产品信息规定了标准剂量。目前的证据表明，在稳态时，治疗性β-内酰胺浓度不一致。这篇综述将探讨替代β-内酰胺剂量优化策略，包括延长输注、基于指南的剂量、治疗药物监测（TDM）和使用剂量优化软件，所有这些都旨在提高达到治疗药物浓度的可能性，并改善临床结局，与标准剂量方法相比。这些剂量优化策略已经成为越来越多证据的主题；然而，需要进一步研究非 TDM 和 TDM 剂量策略的获益和有效性。对于临床医生来说，选择适合个体患者的可行剂量策略很重要，这将最大限度地提高在稳态时达到治疗浓度的可能性，并在整个治疗过程中维持这些暴露。
