Topical antibiotics for otitis media: A one-squirt cure?

otitis media transtympanic gel
A single-application gel could revolutionize treatment of ear infections, reducing side effects and drug resistance. (Click to play animation.) Credit:Kohane group

Otitis media, or middle-ear infection, affects 95 percent of children and is the number one reason for antibiotic prescriptions in pediatrics. Typically, antibiotic treatment involves 7 to 10 days of oral medication — several times a day — a formidable task for parents of little kids.

“Force-feeding antibiotics to a toddler by mouth is like a full-contact martial art,” says Daniel Kohane, MD, PhD, a pediatrician and director of the Laboratory for Biomaterials and Drug Delivery at Boston Children’s Hospital.

A single-application bioengineered gel could be the answer to parents’ and pediatricians’ prayers. Described in a paper published today in Science Translational Medicine, the gel would provide an entire course of therapy through a single squirt into the ear canal. It was developed by Kohane’s team in collaboration with investigators at Boston Medical Center and Massachusetts Eye and Ear.

Reducing resistance, sidelining side effects

One-squirt antibiotic treatment would be more than a convenience. It would potentially reduce antibiotic-resistant infections that can result from abandoning treatment mid-course (often because children appear to be doing better after a few days). Direct, topical delivery would likely eliminate the systemic side effects of oral antibiotics (diarrhea, rashes, oral thrush) and could prevent disturbances in the intestinal microbiome.

“With oral antibiotics, you have to treat the entire body repeatedly just to get to the middle ear,” says Rong Yang, PhD, a chemical engineer in Kohane’s lab and first author on the paper. “With the gel, a pediatrician could administer the entire antibiotic course all at once, and only where it’s needed.”

When Kohane presented his concept and early research a couple of years ago at an international symposium on otitis media, he was stunned by the response.

“Usually you ask, ‘do you have any questions?’ and it’s crickets,” says Kohane. “I’m trying to get off the podium and it’s, like, five deep. I was like a rock star. That’s when I diverted even more resources to this project.”

That included hiring Yang, who dug in on the technical aspects of the project. “Progress has been asymptotic since she took over,” says Kohane.

Penetrating the eardrum

The eardrum (a.k.a. the tympanic membrane) has until now been seen as an impenetrable barrier. To get antibiotics through it, Yang added chemical permeation enhancers (CPEs) to the gel. These compounds, already FDA-approved for other uses, are structurally similar to the lipids in the stratum corneum, the eardrum’s outermost layer. The CPEs insert themselves into this membrane, opening up molecular pores that allow the antibiotics to seep through.

Rong Yang and Dan Kohane, inventors of otitis media transtympanic gel
Yang (left) with Kohane

“Our technology gets things across the eardrum that don’t usually get across,” says Kohane.

The gel starts out as a liquid, but once it contacts something warm (like the eardrum), it quickly hardens and stays in place, gradually dispensing antibiotics across the eardrum into the middle ear. Yang and Kohane demonstrated this in chinchillas, cute rodents that happen to have a hearing range and ear structure similar to those of humans.

The gel, loaded with ciprofloxacin, completely cured ear infections due to Haemophilus influenzae in 10 of 10 animals by day 7. (Ordinary ciprofloxacin ear drops cleared the infection in only 5 of 8 animals.) There was no observable toxicity, and no antibiotic was detected in the animals’ blood. Yang and Kohane observed a slight hearing loss, similar to that caused by earwax. Giving less of the gel alleviated the problem.

An otitis media revolution?

Science Translational Medicine otitis media gel
(Used with permission from AAAS)

The researchers think their invention will revolutionize care of ear infections and advance public health in general.

“Transtympanic delivery of antibiotics to the middle ear has the potential to enable children to benefit from the rapid antibacterial activity of antimicrobial agents without systemic exposure and could reduce emergence of resistant microbes,” says Stephen Pelton, MD, a pediatric infectious disease physician at Boston Medical Center and a coauthor on the paper.

Yang recently won a poster competition at the 2016 Massachusetts Life Sciences Innovation Day. Kohane has received a large, five-year NIH grant to further the work and an award from Boston Children’s Hospital’s Technology Development Fund to move the patented technology toward clinical use.

Though further studies are needed, Kohane hopes to form a company that would begin testing the gel in patients in the next few months.

The study was done in collaboration with the Division of Pediatric Infectious Diseases at Boston Medical Center. Funding was provided by the Center for Integration of Medicine and Innovative Technology (U.S. Army Medical Research Acquisition Activity subcontract #W81XWH-09-2-0001), the Shereta Seelig Charitable Foundation Trust, the National Institutes of Health (DC015050) and the Department of Anesthesia at Boston Children’s Hospital.

If you are a physician with a complex-care patient to refer, call Boston Children’s priority line (1-844-BCH-PEDS).