Department of Pharmacy, Nanjing Drum Tower Hospital, Traditional Chinese and Western Medicine Clinical College, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Pharmacy, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Jul;397(7):4791-4798. doi: 10.1007/s00210-023-02909-4. Epub 2023 Dec 28.
The primary objective of this study was to evaluate the predictors associated with target concentration (non-)attainment of imipenem in critically ill patients. The secondary objective was to explore the correlation between achieving imipenem target concentrations and clinical outcomes of therapy. A retrospective cohort study was conducted in critically ill patients treated with imipenem. Clinical data were extracted from the patients' electronic medical records. The pharmacokinetic/pharmacodynamic target was defined as free imipenem concentrations above the minimum inhibitory concentration (MIC) of the pathogen at 100% (100%fT>MIC) of the dosing interval. Factors associated with the non-attainment of target concentrations were evaluated using binomial logistic regression. Kaplan-Meier analysis was used to investigate the correlation between (non-)attainment targets and 30-day mortality. A total of 406 patients were included, and 55.4% achieved the target of 100%fT>MIC. Regression analysis identified an initial daily dose of imipenem ≤ 2 g/day, augmented renal clearance, age ≤ 60 years, recent surgery, and absence of positive microbiology culture as risk factors for target non-attainment. Achieving the 100%fT>MIC target was significantly associated with clinical efficacy but not with 30-day mortality. Selective application of therapeutic drug monitoring in the early stages of imipenem treatment for critically ill patients can improve clinical outcomes. Further research should explore the potential benefits of TDM-guided dosing strategies for imipenem in critical care settings.
本研究的主要目的是评估与重症患者中碳青霉烯类药物(美罗培南)目标浓度(未)达标相关的预测因素。次要目的是探讨达到美罗培南目标浓度与治疗临床结局的相关性。本研究采用回顾性队列研究方法,纳入接受美罗培南治疗的重症患者。临床数据从患者的电子病历中提取。药代动力学/药效学目标定义为给药间隔 100%时间(fT)时游离美罗培南浓度超过病原体最低抑菌浓度(MIC)的 100%(100%fT>MIC)。使用二项逻辑回归评估与未达标相关的因素。采用 Kaplan-Meier 分析探讨(未)达标与 30 天死亡率之间的关系。共纳入 406 例患者,其中 55.4%达到 100%fT>MIC 的目标。回归分析确定美罗培南初始日剂量≤2 g/天、增强的肾清除率、年龄≤60 岁、近期手术和无阳性微生物培养是未达标目标的危险因素。达到 100%fT>MIC 目标与临床疗效显著相关,但与 30 天死亡率无关。在重症患者美罗培南治疗的早期阶段选择性应用治疗药物监测可改善临床结局。进一步的研究应探索治疗药物监测指导美罗培南剂量策略在重症监护环境中的潜在获益。