Comparison of the accuracy and precision of pharmacokinetic equations to predict free meropenem concentrations in critically ill patients

Gloria Wong, Andras Farkas, Rachel Sussman, Gergely Daroczi, William W. Hope, Jeffrey Lipman, Jason A. Roberts*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract (may include machine translation)

Population pharmacokinetic analyses can be applied to predict optimized dosages for individual patients. The aim of this study was to compare the prediction performance of the published population pharmacokinetic models for meropenem in critically ill patients. We coded the published population pharmacokinetic models with covariate relationships into dosing software to predict unbound meropenem concentrations measured in a separate cohort of critically ill patients. The agreements between the observed and predicted concentrations were evaluated with Bland-Altman plots. The absolute and relative bias and precision of the models were determined. The clinical implications of the results were evaluated according to whether dose adjustments were required from the predictions to achieve a meropenem concentration of > 2 mg/liter throughout the dosing interval. A total of 157 free meropenem concentrations from 56 patients were analyzed. Eight published population pharmacokinetic models were compared. The models showed an absolute bias in predicting the unbound meropenem concentrations from a mean percent difference (95% confidence interval [CI]) of -108.5% (-119.9% to-97.3%) to 19.9% (7.3% to 32.7%), while absolute precision ranged from-249.1% (-263.4% to-234.8%) to 31.9% (17.6% to 46.2%) and-178.9% (-196.9% to-160.9%) to 175.0% (157.0% to 193.0%). A dose change was required in 44% to 64% of the concentration results. Seven of the eight equations evaluated underpredicted free meropenem concentrations. In conclusion, the overall accuracy of these models supports their inclusion in dosing software and application for individualizing meropenem doses in critically ill patients to increase the likelihood of achievement of optimal antibiotic exposures.

Original languageEnglish
Pages (from-to)1411-1417
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume59
Issue number3
DOIs
StatePublished - 1 Mar 2015
Externally publishedYes

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