Over one-quarter of all oral antibiotics prescribed in the United States are for acute otitis media. Tympanostomy tube (TT) insertion has become the treatment of choice for children with recurrent or chronic otitis media, with more than two million tubes sold annually in the US. Tympanostomy is the most common pediatric procedure under general anesthesia in the developed world. Chronic post-tympanostomy tube otorrhea (PTTO) is often refractory to treatment and inflicts significant morbidity in the form of hearing loss and long-term middle ear dysfunction. The Co-investigators have confirmed that chronic middle ear infection is a mucosal biofilm disease, and this may explain why otitis media is often difficult to treat with antibiotics. Biofilm growth on the TT surface and on middle ear mucosa may be a source of recurrent infections, and thus may also be a primary contributor. Between 10% and 50% of children with tubes experience otorrhea, and approximately 25% of children with a primary set of tubes will have to go on to have a second set of tubes. Based on prior studies, we believe that we can reduce the number of episodes and episode duration of PTTO by creating antimicrobial eluting ear tubes based on developing novel materials. We have designed a combination therapy that will provide broad-spectrum activity against planktonic and biofilm-forming species associated with otitis media. The antimicrobials selected will also reduce the likelihood of the development of resistant strains. We have demonstrated in Phase I that we can suppress biofilm formation and planktonic growth of Pseudomonas aeruginosa and Staphylococcus aureus for an extended period of time. By modifying the release kinetics, we believe we can increase this time period of efficacy even further. Our data also suggests that we have a synergistic interaction between antimicrobials. We have also demonstrated that we can make materials which are not cytotoxic to rabbit fibroblasts.
The Specific Aims of this Phase II study are: 1) to optimize the release kinetics of our new materials and to injection mold TTs, 2) to confirm our in vitro studies with Haemophilus influenzae and Streptococcus pneumoniae, and quantify synergy and monitor for the development of resistant strains, 3) to assess ototoxicity, sensitivity and irritation in animal models, and 4) to compare the ability of experimental tubes with control tubes to treat and prevent PTTO in the chinchilla model of otitis media.

Public Health Relevance

In Phase I, we developed a combination of antimicrobial/antibiotic compounds incorporated in host polymers that significantly inhibits bacterial attachment and biofilm development of organisms associated with otitis media. We plan to develop tympanostomy tube materials using such combination strategies and test their safety in an established animal model.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
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Special Emphasis Panel (ZRG1-IDM-M (12))
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Miller, Roger
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Novaflux Technologies, Inc.
United States
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Dukhin, Stanislav S; Labib, Mohamed E (2012) Theory of effective drug release from medical implants based on the Higuchi model and physico-chemical hydrodynamics. Colloids Surf A Physicochem Eng Asp 409:10-20
Labib, Mohamed E; Brumlik, Charles J; Stoodley, Paul et al. (2010) The Long-term Release of Antibiotics From Monolithic Nonporous Polymer Implants for Use as Tympanostomy Tubes. Colloids Surf A Physicochem Eng Asp 254:331-337