Troisi Carla, Cojutti Pier Giorgio, Rinaldi Matteo, Laici Cristiana, Siniscalchi Antonio, Viale Pierluigi, Pea Federico
Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy.
Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
Pharmaceutics. 2023 Feb 7;15(2):551. doi: 10.3390/pharmaceutics15020551.
Assessment of glomerular filtration rate (GFR) is necessary for dose adjustments of beta-lactam that are excreted by the kidneys, such as meropenem. The aim of this study was to compare the daily dose of 24 h-continuous infusion (CI) meropenem when GFR was calculated by means of measured creatinine clearance (mCL) or estimated by the CKDEPI (eGFR), Cockcroft-Gault (eGFR), and MDRD (eGFR) equations. Adult critically ill patients who underwent therapeutic drug monitoring (TDM) for the assessment of 24 h-CI meropenem steady state concentration (Css) and for whom a 24 h-urine collection was performed were retrospectively enrolled. Meropenem clearance (CL) was regressed against mCL, and meropenem daily dose was calculated based on the equation infusion rate = daily dose/CL. eGFR, eGFR, and eGFR were regressed against mCL in order to estimate CL. Forty-six patients who provided 133 meropenem Css were included. eGFR overestimated mCL up to 90 mL/min, then mCL was underestimated. eGFR and eGFR overestimated mCL across the entire range of GFR. In critically ill patients, dose adjustments of 24 h-CI meropenem should be based on mCL. Equations for estimation of GFR may lead to gross under/overestimates of meropenem dosages. TDM may be highly beneficial, especially for critically ill patients with augmented renal clearance.
评估肾小球滤过率(GFR)对于调整经肾脏排泄的β-内酰胺类药物(如美罗培南)的剂量是必要的。本研究的目的是比较当通过测量的肌酐清除率(mCL)计算GFR或通过CKDEPI(eGFR)、Cockcroft-Gault(eGFR)和MDRD(eGFR)方程估算GFR时,24小时持续输注(CI)美罗培南的每日剂量。回顾性纳入了接受治疗药物监测(TDM)以评估24小时CI美罗培南稳态浓度(Css)且进行了24小时尿液收集的成年重症患者。将美罗培南清除率(CL)与mCL进行回归分析,并根据输注速率=每日剂量/CL的公式计算美罗培南的每日剂量。将eGFR、eGFR和eGFR与mCL进行回归分析以估算CL。纳入了提供133次美罗培南Css的46例患者。eGFR在GFR高达90 mL/min时高估了mCL,然后mCL被低估。在整个GFR范围内,eGFR和eGFR均高估了mCL。在重症患者中,24小时CI美罗培南的剂量调整应基于mCL。估算GFR的方程可能导致美罗培南剂量的严重低估/高估。TDM可能非常有益,尤其是对于肾清除率增加的重症患者。