Centre for Medicine Use and Safety, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Drug Delivery, Disposition, and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Clin Pharmacol Ther. 2021 Apr;109(4):892-904. doi: 10.1002/cpt.2203. Epub 2021 Mar 6.
Early initiation of effective antibiotic therapy is vitally important for saving the lives of critically ill patients with sepsis or septic shock. The susceptibility of the infecting pathogen and the ability of the selected dosage regimen to safely achieve the required antibiotic exposure need to be carefully considered to achieve a high probability of a successful outcome. Critically ill patients commonly experience substantial pathophysiological changes that impact the functions of various organs, including the kidneys. Many antibiotics are predominantly renally eliminated and thus renal function is a major determinant of the regimen needed to achieve the required antibiotic exposure. However, currently, there is a paucity of guidelines to inform antibiotic dosing in critically ill patients, including those with sepsis or septic shock. This paper briefly reviews methods that are commonly used in critically ill patients to provide a measure of renal function, and approaches that describe the relationship between the exposure to an antibiotic and its antibacterial effects. Two common conditions that very substantially complicate the use of antibiotics in critically ill patients with sepsis, unstable renal function, and augmented renal clearance, are considered in detail and their potential therapeutic implications are explored. Suggestions are provided on how treatment of bacterial infections in critically ill patients with sepsis might be improved. Of high potential are model-informed approaches that aim to individualize initial treatment regimens based on patient and bacterial characteristics, with refinement of regimens during treatment in response to monitoring antibiotic concentrations, responsive measures of renal function, and other important clinical data.
早期开始有效的抗生素治疗对于拯救患有败血症或感染性休克的重症患者的生命至关重要。需要仔细考虑感染病原体的敏感性和所选剂量方案安全达到所需抗生素暴露的能力，以实现高成功率的结果。重症患者通常会经历大量影响包括肾脏在内的各种器官功能的病理生理变化。许多抗生素主要通过肾脏消除，因此肾功能是确定实现所需抗生素暴露所需方案的主要决定因素。然而，目前，缺乏指导重症患者（包括败血症或感染性休克患者）使用抗生素的指南。本文简要回顾了在重症患者中常用的方法，以提供衡量肾功能的指标，并介绍了描述抗生素暴露与抗菌作用之间关系的方法。详细考虑了两种非常严重的复杂重症感染患者使用抗生素的常见情况，即肾功能不稳定和增强的肾清除，并探讨了它们潜在的治疗意义。就如何改善重症败血症患者细菌感染的治疗提出了建议。具有很高潜力的是基于患者和细菌特征个体化初始治疗方案的模型指导方法，在治疗过程中根据监测抗生素浓度、对肾功能的响应性措施以及其他重要临床数据来调整方案。
