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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2020
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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. |
format | Online Article Text |
id | pubmed-7428333 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
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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