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
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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.
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