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Response of a clinical Escherichia coli strain to repeated cefquinome exposure in a piglet tissue-cage model

BACKGROUND: In order to provide some basis for effective dosage regimens that optimize efficacy with respect to bacteriological and clinical cures, the in vivo activity of cefquinome against a clinical Escherichia coli (E.coli) strain (the minimum inhibitory concentration value for this strain equal...

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Autores principales: Gu, Mengxiao, Zhang, Nan, Zhang, Longfei, Xiong, Mingpeng, Yang, Yuanyuan, Gu, Xiaoyan, Shen, Xiangguang, Ding, Huanzhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514946/
https://www.ncbi.nlm.nih.gov/pubmed/26209108
http://dx.doi.org/10.1186/s12917-015-0486-6
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author Gu, Mengxiao
Zhang, Nan
Zhang, Longfei
Xiong, Mingpeng
Yang, Yuanyuan
Gu, Xiaoyan
Shen, Xiangguang
Ding, Huanzhong
author_facet Gu, Mengxiao
Zhang, Nan
Zhang, Longfei
Xiong, Mingpeng
Yang, Yuanyuan
Gu, Xiaoyan
Shen, Xiangguang
Ding, Huanzhong
author_sort Gu, Mengxiao
collection PubMed
description BACKGROUND: In order to provide some basis for effective dosage regimens that optimize efficacy with respect to bacteriological and clinical cures, the in vivo activity of cefquinome against a clinical Escherichia coli (E.coli) strain (the minimum inhibitory concentration value for this strain equals to the MIC(90) value of 0.25 μg/ml for 210 E.coli strains isolated from pigs) was investigated by using a piglet tissue-cage infection model. The aim was to elucidate the pharmacokinetic/pharmacodynamics (PK/PD) index associated with cefquinome efficacy, and then to identify the magnitude of the PK/PD parameter required for different degree of efficacy in clinical treatment. RESULTS: Tissue-cage infection model was established in piglets, and then the animals received intramuscular injection of cefquinome twice a day for 3 days to create a range of different drug exposures. The tissue-cage fluid was collected at 1, 3, 6, 9 and 12 h after every drug administration for drug concentration determination and bacteria counting. Different cefquinome regimens produced different percentages of time during that drug concentrations exceeded the MIC (%T > MIC), ranging from 0 % to 100 %. Cefquinome administration at 0.2, 0.4, 0.6, 0.8, 1, 2 and 4 mg/kg reduced the bacterial count (log(10) CFU/mL) in tissue-cage fluid by −1.00 ± 0.32, −1.83 ± 0.08, −2.33 ± 0.04, −2.96 ± 0.16, −2.99 ± 0.16, −2.93 ± 0.11, −3.43 ± 0.18, respectively. The correlation coefficient of the PK/PD index with antibacterial effect of the drug was 0.90 for %T > MIC, 0.62 for AUC(0–12)/MIC, and 0.61 for C(max)/MIC, suggesting the most important PK/PD parameter was %T > MIC. A inhibitory form of sigmoid maximum effect (E(max)) model was used to estimate %T > MIC, and the respective values required for continuous 1/6-log drop, 1/3-log drop and 1/2-log drop of the clinical E.coli count during each 12 h treatment period were 3.97 %, 17.08 % and 52.68 %. CONCLUSIONS: The data derived from this study showed that cefquinome exhibited time-dependent killing profile. And from the results of the present study, it can be assumed that when %T > MIC reached 52.68 %, cefquinome could be expected to be effective against a clinical E.coli strain for which the MIC value is below 0.128 μg/ml (3-log drop of bacteria count can be achieved after six successive administrations for 3 days).
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spelling pubmed-45149462015-07-26 Response of a clinical Escherichia coli strain to repeated cefquinome exposure in a piglet tissue-cage model Gu, Mengxiao Zhang, Nan Zhang, Longfei Xiong, Mingpeng Yang, Yuanyuan Gu, Xiaoyan Shen, Xiangguang Ding, Huanzhong BMC Vet Res Research Article BACKGROUND: In order to provide some basis for effective dosage regimens that optimize efficacy with respect to bacteriological and clinical cures, the in vivo activity of cefquinome against a clinical Escherichia coli (E.coli) strain (the minimum inhibitory concentration value for this strain equals to the MIC(90) value of 0.25 μg/ml for 210 E.coli strains isolated from pigs) was investigated by using a piglet tissue-cage infection model. The aim was to elucidate the pharmacokinetic/pharmacodynamics (PK/PD) index associated with cefquinome efficacy, and then to identify the magnitude of the PK/PD parameter required for different degree of efficacy in clinical treatment. RESULTS: Tissue-cage infection model was established in piglets, and then the animals received intramuscular injection of cefquinome twice a day for 3 days to create a range of different drug exposures. The tissue-cage fluid was collected at 1, 3, 6, 9 and 12 h after every drug administration for drug concentration determination and bacteria counting. Different cefquinome regimens produced different percentages of time during that drug concentrations exceeded the MIC (%T > MIC), ranging from 0 % to 100 %. Cefquinome administration at 0.2, 0.4, 0.6, 0.8, 1, 2 and 4 mg/kg reduced the bacterial count (log(10) CFU/mL) in tissue-cage fluid by −1.00 ± 0.32, −1.83 ± 0.08, −2.33 ± 0.04, −2.96 ± 0.16, −2.99 ± 0.16, −2.93 ± 0.11, −3.43 ± 0.18, respectively. The correlation coefficient of the PK/PD index with antibacterial effect of the drug was 0.90 for %T > MIC, 0.62 for AUC(0–12)/MIC, and 0.61 for C(max)/MIC, suggesting the most important PK/PD parameter was %T > MIC. A inhibitory form of sigmoid maximum effect (E(max)) model was used to estimate %T > MIC, and the respective values required for continuous 1/6-log drop, 1/3-log drop and 1/2-log drop of the clinical E.coli count during each 12 h treatment period were 3.97 %, 17.08 % and 52.68 %. CONCLUSIONS: The data derived from this study showed that cefquinome exhibited time-dependent killing profile. And from the results of the present study, it can be assumed that when %T > MIC reached 52.68 %, cefquinome could be expected to be effective against a clinical E.coli strain for which the MIC value is below 0.128 μg/ml (3-log drop of bacteria count can be achieved after six successive administrations for 3 days). BioMed Central 2015-07-25 /pmc/articles/PMC4514946/ /pubmed/26209108 http://dx.doi.org/10.1186/s12917-015-0486-6 Text en © Gu et al. 2015 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
Gu, Mengxiao
Zhang, Nan
Zhang, Longfei
Xiong, Mingpeng
Yang, Yuanyuan
Gu, Xiaoyan
Shen, Xiangguang
Ding, Huanzhong
Response of a clinical Escherichia coli strain to repeated cefquinome exposure in a piglet tissue-cage model
title Response of a clinical Escherichia coli strain to repeated cefquinome exposure in a piglet tissue-cage model
title_full Response of a clinical Escherichia coli strain to repeated cefquinome exposure in a piglet tissue-cage model
title_fullStr Response of a clinical Escherichia coli strain to repeated cefquinome exposure in a piglet tissue-cage model
title_full_unstemmed Response of a clinical Escherichia coli strain to repeated cefquinome exposure in a piglet tissue-cage model
title_short Response of a clinical Escherichia coli strain to repeated cefquinome exposure in a piglet tissue-cage model
title_sort response of a clinical escherichia coli strain to repeated cefquinome exposure in a piglet tissue-cage model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514946/
https://www.ncbi.nlm.nih.gov/pubmed/26209108
http://dx.doi.org/10.1186/s12917-015-0486-6
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