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

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.