美罗培南的药代动力学/药效学变异性与肾功能：“我们紧密相连”

Meropenem PK/PD Variability and Renal Function: "We Go Together".

作者信息

Angelini Jacopo, Giuliano Simone, Flammini Sarah, Pagotto Alberto, Lo Re Francesco, Tascini Carlo, Baraldo Massimo

机构信息

Clinical Pharmacology and Toxicology Institute, University Hospital Friuli Centrale ASUFC, 33100 Udine, Italy.

Department of Medicine, University of Udine (UNIUD), 33100 Udine, Italy.

出版信息

Pharmaceutics. 2023 Aug 30;15(9):2238. doi: 10.3390/pharmaceutics15092238.

BACKGROUND

Meropenem is a carbapenem antibiotic widely employed for serious bacterial infections. Therapeutic drug monitoring (TDM) is a strategy to optimize dosing, especially in critically ill patients. This study aims to show how TDM influences the management of meropenem in a real-life setting, not limited to intensive care units.

METHODS

From December 2021 to February 2022, we retrospectively analyzed 195 meropenem serum concentrations (Css). We characterized patients according to meropenem exposure, focusing on the renal function impact.

RESULTS

A total of 36% ( = 51) of the overall observed patients ( = 144) were in the therapeutic range (8-16 mg/L), whereas 64% ( = 93) required a meropenem dose modification (37 patients (26%) underexposed; 53 (38%) overexposed). We found a strong relationship between renal function and meropenem concentrations (correlation coefficient = -0.7; -value < 0.001). We observed different dose-normalized meropenem exposure (Css/D) among renal-impaired (severe and moderate), normal, and hyperfiltrating patients, with a median (interquartile range) of 13.1 (10.9-20.2), 7.9 (6.1-9.5), 3.8 (2.6-6.0), and 2.4 (1.6-2.7), respectively (-value < 0.001).

CONCLUSIONS

Meropenem TDM in clinical practice allows modification of dosing in patients inadequately exposed to meropenem to maximize antibiotic efficacy and minimize the risk of antibiotic resistance, especially in renal alterations despite standard dose adaptations.

背景

美罗培南是一种广泛用于治疗严重细菌感染的碳青霉烯类抗生素。治疗药物监测（TDM）是一种优化给药剂量的策略，尤其适用于重症患者。本研究旨在展示TDM如何在现实环境中影响美罗培南的管理，且不限于重症监护病房。

方法

2021年12月至2022年2月，我们回顾性分析了195份美罗培南血清浓度（Css）。我们根据美罗培南暴露情况对患者进行特征描述，重点关注肾功能的影响。

结果

在总共观察的144例患者中，有36%（n = 51）处于治疗范围（8 - 16 mg/L），而64%（n = 93）需要调整美罗培南剂量（37例患者（26%）暴露不足；53例（38%）暴露过度）。我们发现肾功能与美罗培南浓度之间存在很强的相关性（相关系数 = -0.7；P值 < 0.001）。我们观察到肾功能受损（重度和中度）、正常和高滤过患者之间不同的剂量标准化美罗培南暴露（Css/D），中位数（四分位间距）分别为13.1（10.9 - 20.2）、7.9（6.1 - 9.5）、3.8（2.6 - 6.0）和2.4（1.6 - 2.7）（P值 < 0.001）。