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A Novel Mouse Model of Chronic Suppurative Otitis Media and Its Use in Preclinical Antibiotic Evaluation Publisher Pubmed



Khomtchouk KM1 ; Kouhi A1, 2 ; Xia A1 ; Bekale LA1 ; Massa SM1 ; Sweere JM3 ; Pletzer D4, 5 ; Hancock RE4 ; Bollyky PL3 ; Santa Maria PL1
Authors
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Authors Affiliations
  1. 1. Department of Otolaryngology, Head and Neck Surgery, Stanford University, Stanford, CA, United States
  2. 2. Department of Otolaryngology Head and Neck Surgery Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Medicine, Infectious Diseases, Stanford University, Stanford, CA, United States
  4. 4. Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
  5. 5. Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand

Source: Science Advances Published:2020


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. Copyright © 2020 The Authors
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