A novel mouse model of chronic suppurative otitis media and its use in preclinical antibiotic evaluation.
Kelly M KhomtchoukAli KouhiAnping XiaLaurent Adonis BekaleSolange M MassaJohanna M SweereDaniel PletzerRobert E W HancockPaul L BollykyPeter L Santa MariaPublished in: Science advances (2020)
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.
Keyphrases
- mouse model
- pseudomonas aeruginosa
- healthcare
- drug induced
- small molecule
- cell therapy
- cystic fibrosis
- staphylococcus aureus
- risk factors
- type diabetes
- machine learning
- young adults
- emergency department
- adipose tissue
- escherichia coli
- quality improvement
- risk assessment
- insulin resistance
- high throughput
- big data
- electronic health record
- climate change
- deep learning
- artificial intelligence
- human health
- high fat diet induced