New horizons in tympanic membrane healing

New horizons in tympanic membrane healing
Ali Kouhi, Peter Santa Maria, Kelly Khomtchouk, Anping Xia
Department of Otolaryngology, Head and Neck Surgery, Stanford University,
Stanford.

Chronic suppurative otitis media (CSOM) is a massive global health problem that has seen little progress in its treatment. CSOM is a chronically infected and discharging middle ear affecting approximately 330 million individuals worldwide. CSOM is more than just uncomfortable – it is a scourge in the developing world. It is the most common cause of persistent hearing loss among children in developing countries, causing hearing loss in more than %50 of cases and it is associated with poor language and cognitive development. In third world countries, CSOM accounts for almost 400 per thousand years of life lost and disability adjusted life years of over 600 per thousand.

Eustachian Tube (ET) dysfunction is recognized as predisposing factor for the development of CSOM. Within the field of otolaryngology, ET occlusion can occur with a variety of other genetic and environmental conditions, including mucocilliary status, allergies, and defective immune responses. We are going to present our mice model for Eustachian tube occlusion and chronic suppurative otitis media. We question the clinical predictive value of in vitro antimicrobial susceptibility tests for biofilm susceptibility and determine, for drugs that freely diffuse through the biofilm matrix, these tests are irrelevant to disease outcome in vivo. In contrast, the in vitro evaluation of antibiotic tolerance with planktonic stationary phase P. aeruginosa predicts the failure and recurrence of fluoroquinolone therapy in CSOM. With our novel mouse biofilm model that allows for bacteria tracking in real-time and topical administration of the standard of care, ofloxacin, we show a cohort of non-responders and a cohort resulting in temporary reduction of bacterial burden, highlighting a problem of recurrence and the need for therapeutic outcomes that assess eradication posttherapeutic endpoint. A new preclinical mouse model of long term gram-negative infection displaying the hallmark features of CSOM, chronic infection leading to inhibition of healing in a perforation of the tympanic membrane and purulent discharge in the ear (as assessed by blinded grading) supports the conclusion that persistent bacteria cells are the bottleneck for eradication in drug tolerant recurrent infections.

In the developed world, a non-surgical treatment would reduce the need for a general anesthetic and outpatient admission for treatment. In the developing world, the problem is larger however access to treatment and surgery contributes to a larger prevalence. Here a non-surgical treatment would provide a treatment option in an area of unmet need. Two other growth factor treatments, fibroblast growth factor (FGF) 2 and epidermal growth factor (EGF) have claimed efficacy in the literature. We will review different options of non-surgical treatment for tympanic membrane healing.