New research was presented at the International Society for Otitis Media meeting in June 2019, which I attended. I would like to share a selection of new findings from the many presentations.
Transtympanic antibiotic delivery
Topical therapy has been used to treat only otitis externa and acute otitis media (AOM) with ear discharge. Giving antibiotics through the tympanic membrane could mitigate many of the concerns about antibiotic use driving antibiotic resistance of bacteria among children. Up to now, using antibiotics in the ear canal to treat AOM has not been considered because the tympanic membrane is highly impermeable to the transtympanic diffusion of any drugs. However, in recent years, a number of different drug delivery systems have been developed, and in some cases, animal studies have shown that noninvasive transtympanic delivery is possible so that drugs can reach high concentrations in the middle ear without damage. Nanovesicles and nanoliposomes that contain antibiotics and are small enough to pass through the eardrum have been developed and tested in animal models; these show promise. Ototopical administration of a drug called vinpocetine that was repurposed has been tested in mice and shown to reduce inflammation and mucus production in the middle ear during otitis media.
Antibiotic treatment failure can occur in AOM for several reasons. The treatment of choice, amoxicillin, for example may fail to achieve an adequate concentration because of poor absorption in the gastrointestinal tract or poor penetration into the middle ear. Or, the antibiotic chosen may not be effective because of resistance of the strain causing the infection. Another explanation, especially in recurrent AOM and chronic AOM, could be the presence of biofilms. Biofilms are multicellular bacterial communities incorporated in a polymeric, plasticlike matrix in which pathogens are protected from antibiotic activity. The biofilm provides a physical barrier to antibiotic penetration, and bacteria can persist in the middle ear and periodically cause a new AOM. If AOM persists or becomes a more chronic otitis media with effusion, the “glue ear” causes an environment in the middle ear that is low in oxygen. A low-oxygen environment is favorable to biofilms. Also one might expect that middle ear pus would have a low pH, but actual measurements show the pH is highly alkaline. Species of Haemophilus influenzae have been identified as more virulent when in an alkaline pH or the alkaline pH makes the H. influenzae persist better in the middle ear, perhaps in a biofilm. To eliminate biofilms and improve antibiotic efficacy, a vaccine against a protein expressed by H. influenzae has been developed. Antibodies against this protein have been shown to disrupt and prevent the formation of biofilms in an animal model.
The normal bacteria that live in the nasopharynx of children with recurrent AOM is now known to differ from that of children who experience infrequent AOM or remain AOM-free throughout childhood. The use of oral pre- and probiotics for AOM prophylaxis remains debated because the results of studies are conflicting and frequently show no effect. So the idea of using prebiotics or probiotics to create a favorable “microbiome” of the nose is under investigation. Two species of bacteria that are gathering the most attention are Corynebacterium species (a few types in particular) and a bacteria called Dolosigranulum pigrum. Delivery of the commensal species would be as a nose spray.