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

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...

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Autores principales: Liebchen, Uwe, Salletmeier, Hanna, Kallee, Simon, Scharf, Christina, Huebner, Lucas, Weber, Alexandra, Zoller, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390684/
https://www.ncbi.nlm.nih.gov/pubmed/34446780
http://dx.doi.org/10.1038/s41598-021-96744-3
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author Liebchen, Uwe
Salletmeier, Hanna
Kallee, Simon
Scharf, Christina
Huebner, Lucas
Weber, Alexandra
Zoller, Michael
author_facet Liebchen, Uwe
Salletmeier, Hanna
Kallee, Simon
Scharf, Christina
Huebner, Lucas
Weber, Alexandra
Zoller, Michael
author_sort Liebchen, Uwe
collection PubMed
description 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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spelling pubmed-83906842021-09-01 Optimal loading dose of meropenem before continuous infusion in critically ill patients: a simulation study Liebchen, Uwe Salletmeier, Hanna Kallee, Simon Scharf, Christina Huebner, Lucas Weber, Alexandra Zoller, Michael Sci Rep Article 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. Nature Publishing Group UK 2021-08-26 /pmc/articles/PMC8390684/ /pubmed/34446780 http://dx.doi.org/10.1038/s41598-021-96744-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Liebchen, Uwe
Salletmeier, Hanna
Kallee, Simon
Scharf, Christina
Huebner, Lucas
Weber, Alexandra
Zoller, Michael
Optimal loading dose of meropenem before continuous infusion in critically ill patients: a simulation study
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390684/
https://www.ncbi.nlm.nih.gov/pubmed/34446780
http://dx.doi.org/10.1038/s41598-021-96744-3
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