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 (CLM) was regressed against mCL(CR), and meropenem daily dose was calculated based on the equation infusion rate = daily dose/CLM. eGFR(CKDEPI), eGFR(CG), and eGFR(CKDEPI) were regressed against mCL(CR) in order to estimate CLM. 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.