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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Bibliographic Details
Published in:	Science advances Vol. 6; no. 33; p. eabc1828
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	United States American Association for the Advancement of Science 01-08-2020
Subjects:	Animals Anti-Bacterial Agents - pharmacology Anti-Bacterial Agents - therapeutic use Disease Models, Animal Diseases and Disorders Humans Mice Ofloxacin Otitis Media, Suppurative - drug therapy Otitis Media, Suppurative - microbiology Persistent Infection Pseudomonas aeruginosa SciAdv r-articles
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	2375-2548 2375-2548
DOI:	10.1126/sciadv.abc1828