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The Epidemiologic and Pharmacodynamic Cutoff Values of Tilmicosin against Haemophilus parasuis
The aim of this study was to establish antimicrobial susceptibility breakpoints for tilmicosin against Haemophilus parasuis, which is an important pathogen of respiratory tract infections. The minimum inhibitory concentrations (MICs) of 103 H. parasuis isolates were determined by the agar dilution m...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802331/ https://www.ncbi.nlm.nih.gov/pubmed/27047487 http://dx.doi.org/10.3389/fmicb.2016.00385 |
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author | Zhang, Peng Hao, Haihong Li, Jun Ahmad, Ijaz Cheng, Guyue Chen, Dongmei Tao, Yanfei Huang, Lingli Wang, Yulian Dai, Menghong Liu, Zhenli Yuan, Zonghui |
author_facet | Zhang, Peng Hao, Haihong Li, Jun Ahmad, Ijaz Cheng, Guyue Chen, Dongmei Tao, Yanfei Huang, Lingli Wang, Yulian Dai, Menghong Liu, Zhenli Yuan, Zonghui |
author_sort | Zhang, Peng |
collection | PubMed |
description | The aim of this study was to establish antimicrobial susceptibility breakpoints for tilmicosin against Haemophilus parasuis, which is an important pathogen of respiratory tract infections. The minimum inhibitory concentrations (MICs) of 103 H. parasuis isolates were determined by the agar dilution method. The wild type (WT) distribution and epidemiologic cutoff value (ECV) were evaluated by statistical analysis. The new bronchoaveolar lavage was used to establish intrapulmonary pharmacokinetic (PK) model in swine. The pharmacokinetic (PK) parameters of tilmicosin, both in pulmonary epithelial lining fluid (PELF) and in plasma, were determined using high performance liquid chromatography method and WinNonlin software. The pharmacodynamic cutoff (CO(PD)) was calculated using Monte Carlo simulation. Our results showed that 100% of WT isolates were covered when the ECV was set at 16 μg/mL. The tilmicosin had concentration-dependent activity against H. parasuis. The PK data indicated that tilmicosin concentrations in PELF was rapidly increased to high levels at 4 h and kept stable until 48 h after drug administration, while the tilmicosin concentration in plasma reached maximum levels at 4 h and continued to decrease during 4–72 h. Using Monte Carlo simulation, CO(PD) was defined as 1 μg/mL. Conclusively, the ECV and CO(PD) of tilmicosin against H. parasuis were established for the first time based on the MIC distribution and PK-PD analysis in the target tissue, respectively. These values are of great importance for detection of tilmicosin-resistant H. parasuis and for effective treatment of clinical intrapulmonary infection caused by H. parasuis. |
format | Online Article Text |
id | pubmed-4802331 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48023312016-04-04 The Epidemiologic and Pharmacodynamic Cutoff Values of Tilmicosin against Haemophilus parasuis Zhang, Peng Hao, Haihong Li, Jun Ahmad, Ijaz Cheng, Guyue Chen, Dongmei Tao, Yanfei Huang, Lingli Wang, Yulian Dai, Menghong Liu, Zhenli Yuan, Zonghui Front Microbiol Microbiology The aim of this study was to establish antimicrobial susceptibility breakpoints for tilmicosin against Haemophilus parasuis, which is an important pathogen of respiratory tract infections. The minimum inhibitory concentrations (MICs) of 103 H. parasuis isolates were determined by the agar dilution method. The wild type (WT) distribution and epidemiologic cutoff value (ECV) were evaluated by statistical analysis. The new bronchoaveolar lavage was used to establish intrapulmonary pharmacokinetic (PK) model in swine. The pharmacokinetic (PK) parameters of tilmicosin, both in pulmonary epithelial lining fluid (PELF) and in plasma, were determined using high performance liquid chromatography method and WinNonlin software. The pharmacodynamic cutoff (CO(PD)) was calculated using Monte Carlo simulation. Our results showed that 100% of WT isolates were covered when the ECV was set at 16 μg/mL. The tilmicosin had concentration-dependent activity against H. parasuis. The PK data indicated that tilmicosin concentrations in PELF was rapidly increased to high levels at 4 h and kept stable until 48 h after drug administration, while the tilmicosin concentration in plasma reached maximum levels at 4 h and continued to decrease during 4–72 h. Using Monte Carlo simulation, CO(PD) was defined as 1 μg/mL. Conclusively, the ECV and CO(PD) of tilmicosin against H. parasuis were established for the first time based on the MIC distribution and PK-PD analysis in the target tissue, respectively. These values are of great importance for detection of tilmicosin-resistant H. parasuis and for effective treatment of clinical intrapulmonary infection caused by H. parasuis. Frontiers Media S.A. 2016-03-22 /pmc/articles/PMC4802331/ /pubmed/27047487 http://dx.doi.org/10.3389/fmicb.2016.00385 Text en Copyright © 2016 Zhang, Hao, Li, Ahmad, Cheng, Chen, Tao, Huang, Wang, Dai, Liu and Yuan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Zhang, Peng Hao, Haihong Li, Jun Ahmad, Ijaz Cheng, Guyue Chen, Dongmei Tao, Yanfei Huang, Lingli Wang, Yulian Dai, Menghong Liu, Zhenli Yuan, Zonghui The Epidemiologic and Pharmacodynamic Cutoff Values of Tilmicosin against Haemophilus parasuis |
title | The Epidemiologic and Pharmacodynamic Cutoff Values of Tilmicosin against Haemophilus parasuis |
title_full | The Epidemiologic and Pharmacodynamic Cutoff Values of Tilmicosin against Haemophilus parasuis |
title_fullStr | The Epidemiologic and Pharmacodynamic Cutoff Values of Tilmicosin against Haemophilus parasuis |
title_full_unstemmed | The Epidemiologic and Pharmacodynamic Cutoff Values of Tilmicosin against Haemophilus parasuis |
title_short | The Epidemiologic and Pharmacodynamic Cutoff Values of Tilmicosin against Haemophilus parasuis |
title_sort | epidemiologic and pharmacodynamic cutoff values of tilmicosin against haemophilus parasuis |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802331/ https://www.ncbi.nlm.nih.gov/pubmed/27047487 http://dx.doi.org/10.3389/fmicb.2016.00385 |
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