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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9228144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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