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Dosing Regimen of Aditoprim and Sulfamethoxazole Combination for the Glaesserella parasuis Containing Resistance and Virulence Genes

Glaesserella parasuis (G. parasuis) causes Glasser’s disease in pigs and causes high mortality in piglets. The new drug Aditoprim (ADP) alone or combined with Sulfamethoxazole (SMZ) is one of the good choices for treating respiratory infections. The objective of this study was to recommend the optim...

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Autores principales: Huang, Anxiong, Huang, Xiao, Zhang, Zhihao, Yuan, Zonghui, Huang, Lingli, Wang, Yulian, Tao, Yanfei, Chen, Dongmei, Liu, Zhenli, Hao, Haihong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9607282/
https://www.ncbi.nlm.nih.gov/pubmed/36297496
http://dx.doi.org/10.3390/pharmaceutics14102058
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author Huang, Anxiong
Huang, Xiao
Zhang, Zhihao
Yuan, Zonghui
Huang, Lingli
Wang, Yulian
Tao, Yanfei
Chen, Dongmei
Liu, Zhenli
Hao, Haihong
author_facet Huang, Anxiong
Huang, Xiao
Zhang, Zhihao
Yuan, Zonghui
Huang, Lingli
Wang, Yulian
Tao, Yanfei
Chen, Dongmei
Liu, Zhenli
Hao, Haihong
author_sort Huang, Anxiong
collection PubMed
description Glaesserella parasuis (G. parasuis) causes Glasser’s disease in pigs and causes high mortality in piglets. The new drug Aditoprim (ADP) alone or combined with Sulfamethoxazole (SMZ) is one of the good choices for treating respiratory infections. The objective of this study was to recommend the optimal dosing regimen for the treatment of G. parasuis infection which contains resistance and virulence genes by ADP/SMZ compound through pharmacokinetics–pharmacodynamics (PK-PD) modeling. The whole genome of the virulent strain G. parasuis H78 was obtained and annotated by whole genome sequencing. The results show that G. parasuis H78 consists of a unilateral circular chromosome with prophages in the genome. The annotation results of G. parasuis H78 showed that the genome contained a large number of virulence-related genes and drug resistance-related genes. The in vitro PD study showed that the antibacterial effect of ADP/SMZ compound against G. parasuis was time-dependent, and AUC/MIC was selected as the PK-PD modeling parameter. The PK study showed that the content of ADP/SMZ compound in pulmonary epithelial lining fluid (PELF) was higher than plasma, and there were no significant differences in ADP and SMZ PK parameters between the healthy and infected group. The dose equation to calculate the optimal dosing regimen of ADP/SMZ compound administration for control of G. parasuis infection was 5/25 mg/kg b.w., intramuscular injection once a day for 3~5 consecutive days. The results of this study provide novel therapeutic options for the treatment of G. parasuis infection to decrease the prevalence and disease burden caused by G. parasuis.
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spelling pubmed-96072822022-10-28 Dosing Regimen of Aditoprim and Sulfamethoxazole Combination for the Glaesserella parasuis Containing Resistance and Virulence Genes Huang, Anxiong Huang, Xiao Zhang, Zhihao Yuan, Zonghui Huang, Lingli Wang, Yulian Tao, Yanfei Chen, Dongmei Liu, Zhenli Hao, Haihong Pharmaceutics Article Glaesserella parasuis (G. parasuis) causes Glasser’s disease in pigs and causes high mortality in piglets. The new drug Aditoprim (ADP) alone or combined with Sulfamethoxazole (SMZ) is one of the good choices for treating respiratory infections. The objective of this study was to recommend the optimal dosing regimen for the treatment of G. parasuis infection which contains resistance and virulence genes by ADP/SMZ compound through pharmacokinetics–pharmacodynamics (PK-PD) modeling. The whole genome of the virulent strain G. parasuis H78 was obtained and annotated by whole genome sequencing. The results show that G. parasuis H78 consists of a unilateral circular chromosome with prophages in the genome. The annotation results of G. parasuis H78 showed that the genome contained a large number of virulence-related genes and drug resistance-related genes. The in vitro PD study showed that the antibacterial effect of ADP/SMZ compound against G. parasuis was time-dependent, and AUC/MIC was selected as the PK-PD modeling parameter. The PK study showed that the content of ADP/SMZ compound in pulmonary epithelial lining fluid (PELF) was higher than plasma, and there were no significant differences in ADP and SMZ PK parameters between the healthy and infected group. The dose equation to calculate the optimal dosing regimen of ADP/SMZ compound administration for control of G. parasuis infection was 5/25 mg/kg b.w., intramuscular injection once a day for 3~5 consecutive days. The results of this study provide novel therapeutic options for the treatment of G. parasuis infection to decrease the prevalence and disease burden caused by G. parasuis. MDPI 2022-09-27 /pmc/articles/PMC9607282/ /pubmed/36297496 http://dx.doi.org/10.3390/pharmaceutics14102058 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
Huang, Anxiong
Huang, Xiao
Zhang, Zhihao
Yuan, Zonghui
Huang, Lingli
Wang, Yulian
Tao, Yanfei
Chen, Dongmei
Liu, Zhenli
Hao, Haihong
Dosing Regimen of Aditoprim and Sulfamethoxazole Combination for the Glaesserella parasuis Containing Resistance and Virulence Genes
title Dosing Regimen of Aditoprim and Sulfamethoxazole Combination for the Glaesserella parasuis Containing Resistance and Virulence Genes
title_full Dosing Regimen of Aditoprim and Sulfamethoxazole Combination for the Glaesserella parasuis Containing Resistance and Virulence Genes
title_fullStr Dosing Regimen of Aditoprim and Sulfamethoxazole Combination for the Glaesserella parasuis Containing Resistance and Virulence Genes
title_full_unstemmed Dosing Regimen of Aditoprim and Sulfamethoxazole Combination for the Glaesserella parasuis Containing Resistance and Virulence Genes
title_short Dosing Regimen of Aditoprim and Sulfamethoxazole Combination for the Glaesserella parasuis Containing Resistance and Virulence Genes
title_sort dosing regimen of aditoprim and sulfamethoxazole combination for the glaesserella parasuis containing resistance and virulence genes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9607282/
https://www.ncbi.nlm.nih.gov/pubmed/36297496
http://dx.doi.org/10.3390/pharmaceutics14102058
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