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A novel mouse model of chronic suppurative otitis media and its use in preclinical antibiotic evaluation
Kelly M Khomtchouk1, Ali Kouhi1,2, Anping Xia1
1Department of Otolaryngology, Head and Neck Surgery, Stanford University, Stanford, CA, USA.
Abstract:
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.
Insights
Researchers developed a novel mouse model for chronic suppurative otitis media (CSOM) to aid in discovering new antimicrobial drugs for this neglected pediatric disease.
Area of Science:
- Infectious Diseases
- Microbiology
- Otolaryngology
Background:
- Chronic suppurative otitis media (CSOM) is a widespread pediatric condition impacting 330 million globally.
- No new therapeutic agents for CSOM have been introduced in over ten years, highlighting an urgent need for novel treatments.
Purpose of the Study:
- To develop and validate a new preclinical mouse model for evaluating drug efficacy and antimicrobial discovery in CSOM.
- To assess the utility of the developed model in mimicking key pathological features of human CSOM.
Main Methods:
- Immune-competent mice underwent tympanic membrane perforation and inoculation with luminescent Pseudomonas aeruginosa.
- Bacterial load was monitored in real-time for 100 days to track infection progression.
- The efficacy of ofloxacin, a standard fluoroquinolone, was evaluated.
Main Results:
- The mouse model successfully replicated hallmark CSOM features, including impaired tympanic membrane healing and purulent discharge.
- Ofloxacin treatment led to a transient decrease in bacterial burden, mirroring clinical challenges with persistent infections.
- Real-time bacterial tracking allowed for dynamic monitoring of infection and treatment response.
Conclusions:
- This novel mouse model provides a valuable platform for preclinical evaluation of new therapies targeting CSOM.
- The model's ability to simulate persistent infection underscores the need for improved therapeutic strategies and outcome measures.
- Further research using this model can accelerate the discovery of effective treatments for this neglected disease.
