Optimization of meropenem dosage in the critically ill population based on renal function

Abstract

This pharmacokinetic model is capable of accurately estimating meropenem concentrations in critically ill patients over a range of CrCl values. Compared with 0.5 h infusions, regimens employing prolonged infusions improved target attainment across all CrCl ranges.

Comparison of the Accuracy and Precision of Pharmacokinetic Equations To Predict Free Meropenem Concentrations in Critically Ill Patients

“…Subjects with a serum creatinine concentration of Ͻ0.4 mg/dl had their creatinine concentration set to 0.4 mg/dl (7). Subjects aged 65 years or older with a serum creatinine concentration of Ͻ0.9 mg/dl had their creatinine values set to 0.9 mg/dl to estimate their creatinine clearance for predictions using the Crandon et al method (9). Dosage and blood sampling histories, including the date, time, dosage, and duration of infusion were also collected.…”

“…Population pharmacokinetic models that quantify the effect of demographic, pathophysiological, and other drug-related factors on drug disposition should be considered valuable in the critical care setting for accurately predicting individualized and optimized antibiotic doses for patients who exhibit profoundly altered and rapidly changing pharmacokinetics. The models can be applied to predict appropriate empirical doses or be used to guide dose adaptation as part of a therapeutic drug monitoring (TDM) intervention.Several pharmacokinetic models have been developed for meropenem from different subpopulations of patients (7)(8)(9)(10)(11)(12)(13)(14). In order to establish a TDM program for meropenem to optimize meropenem dosing, the question arises as to which pharmacokinetic model best predicts the meropenem concentrations in a heterogeneous cohort of critically ill patients.…”

“…Several pharmacokinetic models have been developed for meropenem from different subpopulations of patients (7)(8)(9)(10)(11)(12)(13)(14). In order to establish a TDM program for meropenem to optimize meropenem dosing, the question arises as to which pharmacokinetic model best predicts the meropenem concentrations in a heterogeneous cohort of critically ill patients.…”

Pharmacodynamic Evaluation of the Potential Clinical Utility of Fosfomycin and Meropenem in Combination Therapy against KPC-2-Producing Klebsiella pneumoniae

“…Other studies used a two-compartment model to characterize the total concentration of meropenem in plasma (55)(56)(57)(58). These models were shown to underpredict free meropenem concentrations in critically ill patients, and a onecompartment model had the least bias in predicting free meropenem concentration (21).…”

Optimizing Antibiotic Pharmacodynamics for Clinical Practice

“…In general, the most effective way to optimize these agents, particularly for higher MIC organisms, is to both increase the administered dose and prolong the infusion, thereby maintaining a concentration above higher MICs for the required bactericidal exposure time. This has been applied to β-lactams such as cefepime and meropenem in clinical studies [52,53] Dosages of 2 grams every 8 hours (each dose administered as a 3 hour prolonged infusion) in patients with normal kidney function achieve a high probability of treating organisms considered resistant with MICs of 16 µg/ml and 32 µg/ml for meropenem and cefepime, respectively, which is significantly greater than if the same dosage regimen were infused over the standard 30 minutes.…”