Measuring Creatinine Clearance Is the Most Accurate Way for Calculating the Proper Continuous Infusion Meropenem Dose for Empirical Treatment of Severe Gram-Negative Infections among Critically Ill Patients

Abstract

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_CR) or estimated by the CKDEPI (eGFR_CKDEPI), Cockcroft-Gault (eGFR_CG), and MDRD (eGFR_MDRD) 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_M) was regressed against mCL_CR, and meropenem daily dose was calculated based on the equation infusion rate = daily dose/CL_M. eGFR_CKDEPI, eGFR_CG, and eGFR_CKDEPI were regressed against mCL_CR in order to estimate CL_M. Forty-six patients who provided 133 meropenem Css were included. eGFR_CKDEPI overestimated mCL_CR up to 90 mL/min, then mCL_CR was underestimated. eGFR_CG and eGFR_MDRD overestimated mCL_CR across the entire range of GFR. In critically ill patients, dose adjustments of 24 h-CI meropenem should be based on mCL_CR. 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.

Keywords: continuous infusion meropenem; critically ill patients; therapeutic drug monitoring.