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Pharmacokinetics of Colistin in the Gastrointestinal Tract of Poultry Following Dosing via Drinking Water and Its Bactericidal Impact on Enteric Escherichia coli

Colistin, a last-line antibiotic of major importance in veterinary medicine and of critical importance in human medicine, is authorized to treat gastrointestinal (enteric) infections caused by non-invasive Escherichia coli in multiple veterinary species including poultry. Its use in veterinary medic...

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Autores principales: Mead, Andrew, Richez, Pascal, Azzariti, Stefano, Pelligand, Ludovic
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264055/
https://www.ncbi.nlm.nih.gov/pubmed/34250071
http://dx.doi.org/10.3389/fvets.2021.698135
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author Mead, Andrew
Richez, Pascal
Azzariti, Stefano
Pelligand, Ludovic
author_facet Mead, Andrew
Richez, Pascal
Azzariti, Stefano
Pelligand, Ludovic
author_sort Mead, Andrew
collection PubMed
description Colistin, a last-line antibiotic of major importance in veterinary medicine and of critical importance in human medicine, is authorized to treat gastrointestinal (enteric) infections caused by non-invasive Escherichia coli in multiple veterinary species including poultry. Its use in veterinary medicine has been implicated in the widespread prevalence of mobilized colistin resistance. The objectives of this study were to determine the intestinal content reached in broiler chickens during 72-h treatment with colistin, to evaluate the associated impact on intestinal E. coli density, and to select less susceptible E. coli populations. In this study, 94 broiler chickens were administered a dose of 75,000 IU/kg/day via drinking water. Intestinal samples were collected pre-, during-, and post-dosing. Luminal intestinal content was assessed for colistin content by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), and E. coli were isolated and enumerated on UriSelect agar™. Minimum inhibitory concentration (MIC, for eight isolates per intestine per animal) was determined, and when higher than the epidemiological cutoff (ECOFF 2 mg/l), isolates were screened for mobilized colistin resistance (mcr)-1 to 5. Colistin content increased during treatment to a maximum of 5.09 mg/kg. During this time, the total population of E. coli showed an almost 1,000-fold reduction. An apparent increase in the relative abundance of E. coli with an MIC ≥ ECOFF, either mcr-negative (6.25–10.94%) or mcr-1-positive (4.16–31.25%) was observed, although this susceptibility shift was not maintained post-treatment. Indeed, following cessation of dosing, colistin was eliminated from the intestine, and content was below the limit of quantification (LOQ, 1.1 mg/kg) within 4 h, and the median MIC of E. coli isolates returned below baseline thereafter. Few isolates with a lower susceptibility (mcr-1-positive or negative) were however observed at the end of the study period, indicating maintained sub-populations in the chicken gut. The results of this study show a limited impact on long-term maintenance of less susceptible E. coli populations as a direct result of colistin treatment in individual birds.
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spelling pubmed-82640552021-07-09 Pharmacokinetics of Colistin in the Gastrointestinal Tract of Poultry Following Dosing via Drinking Water and Its Bactericidal Impact on Enteric Escherichia coli Mead, Andrew Richez, Pascal Azzariti, Stefano Pelligand, Ludovic Front Vet Sci Veterinary Science Colistin, a last-line antibiotic of major importance in veterinary medicine and of critical importance in human medicine, is authorized to treat gastrointestinal (enteric) infections caused by non-invasive Escherichia coli in multiple veterinary species including poultry. Its use in veterinary medicine has been implicated in the widespread prevalence of mobilized colistin resistance. The objectives of this study were to determine the intestinal content reached in broiler chickens during 72-h treatment with colistin, to evaluate the associated impact on intestinal E. coli density, and to select less susceptible E. coli populations. In this study, 94 broiler chickens were administered a dose of 75,000 IU/kg/day via drinking water. Intestinal samples were collected pre-, during-, and post-dosing. Luminal intestinal content was assessed for colistin content by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), and E. coli were isolated and enumerated on UriSelect agar™. Minimum inhibitory concentration (MIC, for eight isolates per intestine per animal) was determined, and when higher than the epidemiological cutoff (ECOFF 2 mg/l), isolates were screened for mobilized colistin resistance (mcr)-1 to 5. Colistin content increased during treatment to a maximum of 5.09 mg/kg. During this time, the total population of E. coli showed an almost 1,000-fold reduction. An apparent increase in the relative abundance of E. coli with an MIC ≥ ECOFF, either mcr-negative (6.25–10.94%) or mcr-1-positive (4.16–31.25%) was observed, although this susceptibility shift was not maintained post-treatment. Indeed, following cessation of dosing, colistin was eliminated from the intestine, and content was below the limit of quantification (LOQ, 1.1 mg/kg) within 4 h, and the median MIC of E. coli isolates returned below baseline thereafter. Few isolates with a lower susceptibility (mcr-1-positive or negative) were however observed at the end of the study period, indicating maintained sub-populations in the chicken gut. The results of this study show a limited impact on long-term maintenance of less susceptible E. coli populations as a direct result of colistin treatment in individual birds. Frontiers Media S.A. 2021-06-24 /pmc/articles/PMC8264055/ /pubmed/34250071 http://dx.doi.org/10.3389/fvets.2021.698135 Text en Copyright © 2021 Mead, Richez, Azzariti and Pelligand. https://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) and the copyright owner(s) 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 Veterinary Science
Mead, Andrew
Richez, Pascal
Azzariti, Stefano
Pelligand, Ludovic
Pharmacokinetics of Colistin in the Gastrointestinal Tract of Poultry Following Dosing via Drinking Water and Its Bactericidal Impact on Enteric Escherichia coli
title Pharmacokinetics of Colistin in the Gastrointestinal Tract of Poultry Following Dosing via Drinking Water and Its Bactericidal Impact on Enteric Escherichia coli
title_full Pharmacokinetics of Colistin in the Gastrointestinal Tract of Poultry Following Dosing via Drinking Water and Its Bactericidal Impact on Enteric Escherichia coli
title_fullStr Pharmacokinetics of Colistin in the Gastrointestinal Tract of Poultry Following Dosing via Drinking Water and Its Bactericidal Impact on Enteric Escherichia coli
title_full_unstemmed Pharmacokinetics of Colistin in the Gastrointestinal Tract of Poultry Following Dosing via Drinking Water and Its Bactericidal Impact on Enteric Escherichia coli
title_short Pharmacokinetics of Colistin in the Gastrointestinal Tract of Poultry Following Dosing via Drinking Water and Its Bactericidal Impact on Enteric Escherichia coli
title_sort pharmacokinetics of colistin in the gastrointestinal tract of poultry following dosing via drinking water and its bactericidal impact on enteric escherichia coli
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264055/
https://www.ncbi.nlm.nih.gov/pubmed/34250071
http://dx.doi.org/10.3389/fvets.2021.698135
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