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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-9854650 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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