Optimal loading dose of meropenem before continuous infusion in critically ill patients: a simulation study

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. Ma...

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Autores principales:	Uwe Liebchen, Hanna Salletmeier, Simon Kallee, Christina Scharf, Lucas Huebner, Alexandra Weber, Michael Zoller
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/35be4501d4fa47959d11c96691e45305
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spelling	oai:doaj.org-article:35be4501d4fa47959d11c96691e453052021-12-02T16:34:53ZOptimal loading dose of meropenem before continuous infusion in critically ill patients: a simulation study10.1038/s41598-021-96744-32045-2322https://doaj.org/article/35be4501d4fa47959d11c96691e453052021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96744-3https://doaj.org/toc/2045-2322Abstract 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.Uwe LiebchenHanna SalletmeierSimon KalleeChristina ScharfLucas HuebnerAlexandra WeberMichael ZollerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-6 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Uwe Liebchen Hanna Salletmeier Simon Kallee Christina Scharf Lucas Huebner Alexandra Weber Michael Zoller Optimal loading dose of meropenem before continuous infusion in critically ill patients: a simulation study
description	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.
format	article
author	Uwe Liebchen Hanna Salletmeier Simon Kallee Christina Scharf Lucas Huebner Alexandra Weber Michael Zoller
author_facet	Uwe Liebchen Hanna Salletmeier Simon Kallee Christina Scharf Lucas Huebner Alexandra Weber Michael Zoller
author_sort	Uwe Liebchen
title	Optimal loading dose of meropenem before continuous infusion in critically ill patients: a simulation study
title_short	Optimal loading dose of meropenem before continuous infusion in critically ill patients: a simulation study
title_full	Optimal loading dose of meropenem before continuous infusion in critically ill patients: a simulation study
title_fullStr	Optimal loading dose of meropenem before continuous infusion in critically ill patients: a simulation study
title_full_unstemmed	Optimal loading dose of meropenem before continuous infusion in critically ill patients: a simulation study
title_sort	optimal loading dose of meropenem before continuous infusion in critically ill patients: a simulation study
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/35be4501d4fa47959d11c96691e45305
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Optimal loading dose of meropenem before continuous infusion in critically ill patients: a simulation study

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