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

Does Cytokine-Release Syndrome Induced by CAR T-Cell Treatment Have an Impact on the Pharmacokinetics of Meropenem and Piperacillin/Tazobactam in Patients with Hematological Malignancies? Findings from an Observational Case-Control Study

“…This finding is in contrast to expectations based on previous data, which shows that eGFR is a significant covariate on both meropenem and piperacillin/tazobactam clearance in different patients populations, including oncohematological patients [ 16 , 17 ]. However, eGFR was recently reported to account for no more than 54% of the variability of meropenem elimination in critically ill patients [ 43 ], as this antibiotic is also eliminated by tubular secretion [ 44 ]. With regard to piperacillin clearance, several studies show saturative elimination occurs at therapeutic dosages, which makes drug exposure unpredictable and uncorrelated to eGFR [ 17 ].…”

Meropenem PK/PD Variability and Renal Function: “We Go Together”

“…This confirms the clinical and pharmacological importance of renal function, which is one of the most important parameters that significantly influences exposure to meropenem, and our data suggest physicians take into consideration this parameter, especially in hospitals where TDM is not available. In our study, we used the Cockroft–Gault equation to estimate creatinine clearance, which we chose as the surrogate outcome of glomerular filtration rate, although the measured creatinine clearance should be preferred in critically ill patients because it is more accurate [ 35 ]. The relevance of the impact of renal function is shown by the differences we evidenced in terms of meropenem concentrations, normalized for the daily dose administered, when we compared patients grouped by glomerular function.…”