Abstract：
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.
摘要：
本研究的主要目的是评估危重患者中与亚胺培南目标浓度（非）达到相关的预测因子。次要目的是探讨达到亚胺培南目标浓度与治疗临床结果之间的相关性。在接受亚胺培南治疗的危重患者中进行了一项回顾性队列研究。从患者的电子病历中提取临床数据。药代动力学/药效学目标定义为在给药间隔的100%(100%fT>MIC)时高于病原体的最小抑制浓度(MIC)的游离亚胺培南浓度。使用二项逻辑回归评估与未达到目标浓度相关的因素。使用Kaplan-Meier分析来研究(非)达到目标与30天死亡率之间的相关性。共纳入406例患者，55.4%达到100%fT>MIC的目标。回归分析确定亚胺培南的初始日剂量≤2g/天，增强肾脏清除率，年龄≤60岁，最近的手术,以及缺乏阳性微生物学培养作为目标未达到的危险因素。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。在危重患者亚胺培南治疗早期选择性应用治疗药物监测可改善临床预后。进一步的研究应探索TDM指导的亚胺培南给药策略在重症监护环境中的潜在益处。
