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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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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). |
format | Online Article Text |
id | pubmed-4514946 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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