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Development of a Predictive Dosing Nomogram to Achieve PK/PD Targets of Amikacin Initial Dose in Critically Ill Patients: A Non-Parametric Approach

French guidelines recommend reaching an amikacin concentration of ≥8 × MIC 1 h after beginning infusion (C(1h)), with MIC = 8 mg/L for probabilistic therapy. We aimed to elaborate a nomogram guiding clinicians in choosing the right first amikacin dose for ICU patients in septic shock. A total of 138...

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Autores principales: Coste, Anne, Bellouard, Ronan, Deslandes, Guillaume, Jalin, Laurence, Roger, Claire, Ansart, Séverine, Dailly, Eric, Bretonnière, Cédric, Grégoire, Matthieu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854650/
https://www.ncbi.nlm.nih.gov/pubmed/36671324
http://dx.doi.org/10.3390/antibiotics12010123
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author Coste, Anne
Bellouard, Ronan
Deslandes, Guillaume
Jalin, Laurence
Roger, Claire
Ansart, Séverine
Dailly, Eric
Bretonnière, Cédric
Grégoire, Matthieu
author_facet Coste, Anne
Bellouard, Ronan
Deslandes, Guillaume
Jalin, Laurence
Roger, Claire
Ansart, Séverine
Dailly, Eric
Bretonnière, Cédric
Grégoire, Matthieu
author_sort Coste, Anne
collection PubMed
description French guidelines recommend reaching an amikacin concentration of ≥8 × MIC 1 h after beginning infusion (C(1h)), with MIC = 8 mg/L for probabilistic therapy. We aimed to elaborate a nomogram guiding clinicians in choosing the right first amikacin dose for ICU patients in septic shock. A total of 138 patients with 407 observations were prospectively recruited. A population pharmacokinetic model was built using a non-parametric, non-linear mixed-effects approach. The total body weight (TBW) influenced the central compartment volume, and the glomerular filtration rate (according to the CKD–EPI formula) influenced its clearance. A dosing nomogram was produced using Monte Carlo simulations of the amikacin amount needed to achieve a C(1h) ≥ 8 × MIC. The dosing nomogram recommended amikacin doses from 1700 mg to 4200 mg and from 28 mg/kg to 49 mg/kg depending on the patient’s TBW and renal clearance. However, a C(through) ≤ 2.5 mg/L 24 h and 48 h after an optimal dose of amikacin was obtained with probabilities of 0.20 and 0.81, respectively. Doses ≥ 30 mg/kg are required to achieve a C(1h) ≥ 8 × MIC with MIC = 8 mg/L. Targeting a MIC = 8 mg/L should depend on local ecology.
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spelling pubmed-98546502023-01-21 Development of a Predictive Dosing Nomogram to Achieve PK/PD Targets of Amikacin Initial Dose in Critically Ill Patients: A Non-Parametric Approach Coste, Anne Bellouard, Ronan Deslandes, Guillaume Jalin, Laurence Roger, Claire Ansart, Séverine Dailly, Eric Bretonnière, Cédric Grégoire, Matthieu Antibiotics (Basel) Article French guidelines recommend reaching an amikacin concentration of ≥8 × MIC 1 h after beginning infusion (C(1h)), with MIC = 8 mg/L for probabilistic therapy. We aimed to elaborate a nomogram guiding clinicians in choosing the right first amikacin dose for ICU patients in septic shock. A total of 138 patients with 407 observations were prospectively recruited. A population pharmacokinetic model was built using a non-parametric, non-linear mixed-effects approach. The total body weight (TBW) influenced the central compartment volume, and the glomerular filtration rate (according to the CKD–EPI formula) influenced its clearance. A dosing nomogram was produced using Monte Carlo simulations of the amikacin amount needed to achieve a C(1h) ≥ 8 × MIC. The dosing nomogram recommended amikacin doses from 1700 mg to 4200 mg and from 28 mg/kg to 49 mg/kg depending on the patient’s TBW and renal clearance. However, a C(through) ≤ 2.5 mg/L 24 h and 48 h after an optimal dose of amikacin was obtained with probabilities of 0.20 and 0.81, respectively. Doses ≥ 30 mg/kg are required to achieve a C(1h) ≥ 8 × MIC with MIC = 8 mg/L. Targeting a MIC = 8 mg/L should depend on local ecology. MDPI 2023-01-09 /pmc/articles/PMC9854650/ /pubmed/36671324 http://dx.doi.org/10.3390/antibiotics12010123 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Coste, Anne
Bellouard, Ronan
Deslandes, Guillaume
Jalin, Laurence
Roger, Claire
Ansart, Séverine
Dailly, Eric
Bretonnière, Cédric
Grégoire, Matthieu
Development of a Predictive Dosing Nomogram to Achieve PK/PD Targets of Amikacin Initial Dose in Critically Ill Patients: A Non-Parametric Approach
title Development of a Predictive Dosing Nomogram to Achieve PK/PD Targets of Amikacin Initial Dose in Critically Ill Patients: A Non-Parametric Approach
title_full Development of a Predictive Dosing Nomogram to Achieve PK/PD Targets of Amikacin Initial Dose in Critically Ill Patients: A Non-Parametric Approach
title_fullStr Development of a Predictive Dosing Nomogram to Achieve PK/PD Targets of Amikacin Initial Dose in Critically Ill Patients: A Non-Parametric Approach
title_full_unstemmed Development of a Predictive Dosing Nomogram to Achieve PK/PD Targets of Amikacin Initial Dose in Critically Ill Patients: A Non-Parametric Approach
title_short Development of a Predictive Dosing Nomogram to Achieve PK/PD Targets of Amikacin Initial Dose in Critically Ill Patients: A Non-Parametric Approach
title_sort development of a predictive dosing nomogram to achieve pk/pd targets of amikacin initial dose in critically ill patients: a non-parametric approach
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854650/
https://www.ncbi.nlm.nih.gov/pubmed/36671324
http://dx.doi.org/10.3390/antibiotics12010123
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