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Probability of Target Attainment of Tobramycin Treatment in Acute and Chronic Pseudomonas aeruginosa Lung Infection Based on Preclinical Population Pharmacokinetic Modeling

Biofilms and infectious process may alter free antimicrobial concentrations at the site of infection. Tobramycin (TOB), an aminoglycoside used to treat lung infections caused by Pseudomonas aeruginosa, binds to alginate present in biofilm extracellular matrix increasing its minimum inhibitory concen...

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Autores principales: Dias, Bruna Bernar, Carreño, Fernando, Helfer, Victória Etges, Garzella, Priscila Martini Bernardi, de Lima, Daiane Maria Fonseca, Barreto, Fabiano, de Araújo, Bibiana Verlindo, Dalla Costa, Teresa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228144/
https://www.ncbi.nlm.nih.gov/pubmed/35745809
http://dx.doi.org/10.3390/pharmaceutics14061237
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author Dias, Bruna Bernar
Carreño, Fernando
Helfer, Victória Etges
Garzella, Priscila Martini Bernardi
de Lima, Daiane Maria Fonseca
Barreto, Fabiano
de Araújo, Bibiana Verlindo
Dalla Costa, Teresa
author_facet Dias, Bruna Bernar
Carreño, Fernando
Helfer, Victória Etges
Garzella, Priscila Martini Bernardi
de Lima, Daiane Maria Fonseca
Barreto, Fabiano
de Araújo, Bibiana Verlindo
Dalla Costa, Teresa
author_sort Dias, Bruna Bernar
collection PubMed
description Biofilms and infectious process may alter free antimicrobial concentrations at the site of infection. Tobramycin (TOB), an aminoglycoside used to treat lung infections caused by Pseudomonas aeruginosa, binds to alginate present in biofilm extracellular matrix increasing its minimum inhibitory concentration (MIC). This work aimed to investigate the impact of biofilm-forming P. aeruginosa infection on TOB lung and epithelial lining fluid (ELF) penetration, using microdialysis, and to develop a population pharmacokinetic (popPK) model to evaluate the probability of therapeutic target attainment of current dosing regimens employed in fibrocystic and non-fibrocystic patients. The popPK model developed has three compartments including the lung. The ELF concentrations were described by a penetration factor derived from the lung compartment. Infection was a covariate in lung volume (V3) and only chronic infection was a covariate in central volume (V1) and total clearance (CL). Simulations of the recommended treatments for acute and chronic infection achieved >90% probability of target attainment (PTA) in the lung with 4.5 mg/kg q24h and 11 mg/kg q24h, respectively, for the most prevalent P. aeruginosa MIC (0.5 mg/mL). The popPK model was successfully applied to evaluate the PTA of current TOB dosing regimens used in the clinic, indicating the need to investigate alternative posology.
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spelling pubmed-92281442022-06-25 Probability of Target Attainment of Tobramycin Treatment in Acute and Chronic Pseudomonas aeruginosa Lung Infection Based on Preclinical Population Pharmacokinetic Modeling Dias, Bruna Bernar Carreño, Fernando Helfer, Victória Etges Garzella, Priscila Martini Bernardi de Lima, Daiane Maria Fonseca Barreto, Fabiano de Araújo, Bibiana Verlindo Dalla Costa, Teresa Pharmaceutics Article Biofilms and infectious process may alter free antimicrobial concentrations at the site of infection. Tobramycin (TOB), an aminoglycoside used to treat lung infections caused by Pseudomonas aeruginosa, binds to alginate present in biofilm extracellular matrix increasing its minimum inhibitory concentration (MIC). This work aimed to investigate the impact of biofilm-forming P. aeruginosa infection on TOB lung and epithelial lining fluid (ELF) penetration, using microdialysis, and to develop a population pharmacokinetic (popPK) model to evaluate the probability of therapeutic target attainment of current dosing regimens employed in fibrocystic and non-fibrocystic patients. The popPK model developed has three compartments including the lung. The ELF concentrations were described by a penetration factor derived from the lung compartment. Infection was a covariate in lung volume (V3) and only chronic infection was a covariate in central volume (V1) and total clearance (CL). Simulations of the recommended treatments for acute and chronic infection achieved >90% probability of target attainment (PTA) in the lung with 4.5 mg/kg q24h and 11 mg/kg q24h, respectively, for the most prevalent P. aeruginosa MIC (0.5 mg/mL). The popPK model was successfully applied to evaluate the PTA of current TOB dosing regimens used in the clinic, indicating the need to investigate alternative posology. MDPI 2022-06-11 /pmc/articles/PMC9228144/ /pubmed/35745809 http://dx.doi.org/10.3390/pharmaceutics14061237 Text en © 2022 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
Dias, Bruna Bernar
Carreño, Fernando
Helfer, Victória Etges
Garzella, Priscila Martini Bernardi
de Lima, Daiane Maria Fonseca
Barreto, Fabiano
de Araújo, Bibiana Verlindo
Dalla Costa, Teresa
Probability of Target Attainment of Tobramycin Treatment in Acute and Chronic Pseudomonas aeruginosa Lung Infection Based on Preclinical Population Pharmacokinetic Modeling
title Probability of Target Attainment of Tobramycin Treatment in Acute and Chronic Pseudomonas aeruginosa Lung Infection Based on Preclinical Population Pharmacokinetic Modeling
title_full Probability of Target Attainment of Tobramycin Treatment in Acute and Chronic Pseudomonas aeruginosa Lung Infection Based on Preclinical Population Pharmacokinetic Modeling
title_fullStr Probability of Target Attainment of Tobramycin Treatment in Acute and Chronic Pseudomonas aeruginosa Lung Infection Based on Preclinical Population Pharmacokinetic Modeling
title_full_unstemmed Probability of Target Attainment of Tobramycin Treatment in Acute and Chronic Pseudomonas aeruginosa Lung Infection Based on Preclinical Population Pharmacokinetic Modeling
title_short Probability of Target Attainment of Tobramycin Treatment in Acute and Chronic Pseudomonas aeruginosa Lung Infection Based on Preclinical Population Pharmacokinetic Modeling
title_sort probability of target attainment of tobramycin treatment in acute and chronic pseudomonas aeruginosa lung infection based on preclinical population pharmacokinetic modeling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228144/
https://www.ncbi.nlm.nih.gov/pubmed/35745809
http://dx.doi.org/10.3390/pharmaceutics14061237
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