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A novel mouse model of chronic suppurative otitis media and its use in preclinical antibiotic evaluation

Chronic suppurative otitis media (CSOM) is a neglected pediatric disease affecting 330 million worldwide for which no new drugs have been introduced for over a decade. We developed a mouse model with utility in preclinical drug evaluation and antimicrobial discovery. Our model used immune-competent...

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Autores principales: Khomtchouk, Kelly M., Kouhi, Ali, Xia, Anping, Bekale, Laurent Adonis, Massa, Solange M., Sweere, Jolien M., Pletzer, Daniel, Hancock, Robert E., Bollyky, Paul L., Santa Maria, Peter L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428333/
https://www.ncbi.nlm.nih.gov/pubmed/32851190
http://dx.doi.org/10.1126/sciadv.abc1828
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author Khomtchouk, Kelly M.
Kouhi, Ali
Xia, Anping
Bekale, Laurent Adonis
Massa, Solange M.
Sweere, Jolien M.
Pletzer, Daniel
Hancock, Robert E.
Bollyky, Paul L.
Santa Maria, Peter L.
author_facet Khomtchouk, Kelly M.
Kouhi, Ali
Xia, Anping
Bekale, Laurent Adonis
Massa, Solange M.
Sweere, Jolien M.
Pletzer, Daniel
Hancock, Robert E.
Bollyky, Paul L.
Santa Maria, Peter L.
author_sort Khomtchouk, Kelly M.
collection PubMed
description Chronic suppurative otitis media (CSOM) is a neglected pediatric disease affecting 330 million worldwide for which no new drugs have been introduced for over a decade. We developed a mouse model with utility in preclinical drug evaluation and antimicrobial discovery. Our model used immune-competent mice, tympanic membrane perforation and inoculation with luminescent Pseudomonas aeruginosa that enabled bacterial abundance tracking in real-time for 100 days. The resulting chronic infection exhibited hallmark features of clinical CSOM, including inhibition of tympanic membrane healing and purulent ear discharge. We evaluated the standard care fluoroquinolone ofloxacin and demonstrated that this therapy resulted in a temporary reduction of bacterial burden. These data are consistent with the clinical problem of persistent infection in CSOM and the need for therapeutic outcome measures that assess eradication post-therapeutic endpoint. We conclude that this novel mouse model of CSOM has value in investigating new potential therapies.
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spelling pubmed-74283332020-08-25 A novel mouse model of chronic suppurative otitis media and its use in preclinical antibiotic evaluation Khomtchouk, Kelly M. Kouhi, Ali Xia, Anping Bekale, Laurent Adonis Massa, Solange M. Sweere, Jolien M. Pletzer, Daniel Hancock, Robert E. Bollyky, Paul L. Santa Maria, Peter L. Sci Adv Research Articles Chronic suppurative otitis media (CSOM) is a neglected pediatric disease affecting 330 million worldwide for which no new drugs have been introduced for over a decade. We developed a mouse model with utility in preclinical drug evaluation and antimicrobial discovery. Our model used immune-competent mice, tympanic membrane perforation and inoculation with luminescent Pseudomonas aeruginosa that enabled bacterial abundance tracking in real-time for 100 days. The resulting chronic infection exhibited hallmark features of clinical CSOM, including inhibition of tympanic membrane healing and purulent ear discharge. We evaluated the standard care fluoroquinolone ofloxacin and demonstrated that this therapy resulted in a temporary reduction of bacterial burden. These data are consistent with the clinical problem of persistent infection in CSOM and the need for therapeutic outcome measures that assess eradication post-therapeutic endpoint. We conclude that this novel mouse model of CSOM has value in investigating new potential therapies. American Association for the Advancement of Science 2020-08-14 /pmc/articles/PMC7428333/ /pubmed/32851190 http://dx.doi.org/10.1126/sciadv.abc1828 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Khomtchouk, Kelly M.
Kouhi, Ali
Xia, Anping
Bekale, Laurent Adonis
Massa, Solange M.
Sweere, Jolien M.
Pletzer, Daniel
Hancock, Robert E.
Bollyky, Paul L.
Santa Maria, Peter L.
A novel mouse model of chronic suppurative otitis media and its use in preclinical antibiotic evaluation
title A novel mouse model of chronic suppurative otitis media and its use in preclinical antibiotic evaluation
title_full A novel mouse model of chronic suppurative otitis media and its use in preclinical antibiotic evaluation
title_fullStr A novel mouse model of chronic suppurative otitis media and its use in preclinical antibiotic evaluation
title_full_unstemmed A novel mouse model of chronic suppurative otitis media and its use in preclinical antibiotic evaluation
title_short A novel mouse model of chronic suppurative otitis media and its use in preclinical antibiotic evaluation
title_sort novel mouse model of chronic suppurative otitis media and its use in preclinical antibiotic evaluation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428333/
https://www.ncbi.nlm.nih.gov/pubmed/32851190
http://dx.doi.org/10.1126/sciadv.abc1828
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