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Liebchen, Uwe; Salletmeier, Hanna; Kallee, Simon; Scharf, Christina; Huebner, Lucas; Weber, Alexandra und Zoller, Michael (2021): Optimal loading dose of meropenem before continuous infusion in critically ill patients: a simulation study. In: Scientific reports, Bd. 11, Nr. 1, 17211 [PDF, 1MB]

Abstract

The aim of this study was to investigate optimal loading doses prior to continuous infusion of meropenem in critically ill patients. A previously published and successfully evaluated pharmacokinetic model of critically ill patients was used for stochastic simulations of virtual patients. Maintenance doses administered as continuous infusion of 1.5-6~g/24~h with preceding loading doses (administered as 30~min infusion) of 0.15-2~g were investigated. In addition to the examination of the influence of individual covariates, a best-case and worst-case scenario were simulated. Dosing regimens were considered adequate if the 5th percentile of the concentration-time profile did not drop at any time below four times the S/I breakpoint (= 2~mg/L) of Pseudomonas aeruginosa according to the EUCAST definition. Low albumin concentrations, high body weight and high creatinine clearances increased the required loading dose. A maximum loading dose of 0.33~g resulted in sufficient plasma concentrations when only one covariate showed extreme values. If all three covariates showed extreme values (= worst-case scenario), a loading dose of 0.5~g was necessary. Higher loading doses did not lead to further improvements of target attainment. We recommend the administration of a loading dose of 0.5~g meropenem over 30~min immediately followed by continuous infusion.

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