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.