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In vivo evaluation of mutant selection window of cefquinome against Escherichia coli in piglet tissue-cage model

BACKGROUND: The resistance of cephalosporins is significantly serious in veterinary clinic. In order to inhibit the bacterial resistance production, the mutant selection window (MSW) hypothesis with Escherichia coli (E. coli) ATCC 25922 exposed to cefquinome in an animal tissue-cage model was invest...

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Autores principales: Zhang, Bingxu, Gu, Xiaoyan, Li, Yafei, Li, Xiaohong, Gu, Mengxiao, Zhang, Nan, Shen, Xiangguang, Ding, Huanzhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279896/
https://www.ncbi.nlm.nih.gov/pubmed/25511985
http://dx.doi.org/10.1186/s12917-014-0297-1
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author Zhang, Bingxu
Gu, Xiaoyan
Li, Yafei
Li, Xiaohong
Gu, Mengxiao
Zhang, Nan
Shen, Xiangguang
Ding, Huanzhong
author_facet Zhang, Bingxu
Gu, Xiaoyan
Li, Yafei
Li, Xiaohong
Gu, Mengxiao
Zhang, Nan
Shen, Xiangguang
Ding, Huanzhong
author_sort Zhang, Bingxu
collection PubMed
description BACKGROUND: The resistance of cephalosporins is significantly serious in veterinary clinic. In order to inhibit the bacterial resistance production, the mutant selection window (MSW) hypothesis with Escherichia coli (E. coli) ATCC 25922 exposed to cefquinome in an animal tissue-cage model was investigated. RESULTS: Localized infection with E. coli was established in piglets, and the infected animals were administrated intramuscularly with various doses and intervals of cefquinome to provide antibiotic concentrations below the MIC(99), between the MIC(99) and the mutant prevention concentration (MPC), and above the MPC. E. coli lost susceptibility when drug concentrations fluctuated between the lower and upper boundaries of the window, which defined in vitro as the MIC(99) (0.06 μg/mL) and the MPC (0.16 μg/mL) respectively. For PK/PD parameters, there were no mutant selection enrichment when T>MIC(99) was ≤ 25% or T>MPC was ≥ 50% of administration interval. When T>MIC(99) was > 25% and T>MPC was <50% of administration interval, resistance selection was observed. When AUC(24 h)/MIC(99) and AUC(24 h)/MPC were considered, the mutant selection window extended from 32.84 h to 125.64 h and from 12.83 h to 49.09 h, respectively. CONCLUSIONS: These findings demonstrate that the MSW exists in vivo for time-dependent antimicrobial agents, and its boundaries fit well with those determined in vitro. Maintenance of antimicrobial concentrations above the MPC for > 50% of administration interval is a straightforward way to restrict the acquisition of resistance in this tissue cage model. This situation was achieved with daily intramuscular doses of 1 mg cefquinome/kg body weight.
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spelling pubmed-42798962014-12-31 In vivo evaluation of mutant selection window of cefquinome against Escherichia coli in piglet tissue-cage model Zhang, Bingxu Gu, Xiaoyan Li, Yafei Li, Xiaohong Gu, Mengxiao Zhang, Nan Shen, Xiangguang Ding, Huanzhong BMC Vet Res Research Article BACKGROUND: The resistance of cephalosporins is significantly serious in veterinary clinic. In order to inhibit the bacterial resistance production, the mutant selection window (MSW) hypothesis with Escherichia coli (E. coli) ATCC 25922 exposed to cefquinome in an animal tissue-cage model was investigated. RESULTS: Localized infection with E. coli was established in piglets, and the infected animals were administrated intramuscularly with various doses and intervals of cefquinome to provide antibiotic concentrations below the MIC(99), between the MIC(99) and the mutant prevention concentration (MPC), and above the MPC. E. coli lost susceptibility when drug concentrations fluctuated between the lower and upper boundaries of the window, which defined in vitro as the MIC(99) (0.06 μg/mL) and the MPC (0.16 μg/mL) respectively. For PK/PD parameters, there were no mutant selection enrichment when T>MIC(99) was ≤ 25% or T>MPC was ≥ 50% of administration interval. When T>MIC(99) was > 25% and T>MPC was <50% of administration interval, resistance selection was observed. When AUC(24 h)/MIC(99) and AUC(24 h)/MPC were considered, the mutant selection window extended from 32.84 h to 125.64 h and from 12.83 h to 49.09 h, respectively. CONCLUSIONS: These findings demonstrate that the MSW exists in vivo for time-dependent antimicrobial agents, and its boundaries fit well with those determined in vitro. Maintenance of antimicrobial concentrations above the MPC for > 50% of administration interval is a straightforward way to restrict the acquisition of resistance in this tissue cage model. This situation was achieved with daily intramuscular doses of 1 mg cefquinome/kg body weight. BioMed Central 2014-12-16 /pmc/articles/PMC4279896/ /pubmed/25511985 http://dx.doi.org/10.1186/s12917-014-0297-1 Text en © Zhang et al.; licensee BioMed Central. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zhang, Bingxu
Gu, Xiaoyan
Li, Yafei
Li, Xiaohong
Gu, Mengxiao
Zhang, Nan
Shen, Xiangguang
Ding, Huanzhong
In vivo evaluation of mutant selection window of cefquinome against Escherichia coli in piglet tissue-cage model
title In vivo evaluation of mutant selection window of cefquinome against Escherichia coli in piglet tissue-cage model
title_full In vivo evaluation of mutant selection window of cefquinome against Escherichia coli in piglet tissue-cage model
title_fullStr In vivo evaluation of mutant selection window of cefquinome against Escherichia coli in piglet tissue-cage model
title_full_unstemmed In vivo evaluation of mutant selection window of cefquinome against Escherichia coli in piglet tissue-cage model
title_short In vivo evaluation of mutant selection window of cefquinome against Escherichia coli in piglet tissue-cage model
title_sort in vivo evaluation of mutant selection window of cefquinome against escherichia coli in piglet tissue-cage model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279896/
https://www.ncbi.nlm.nih.gov/pubmed/25511985
http://dx.doi.org/10.1186/s12917-014-0297-1
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