Middle ear infections (Otitis Media, OM) are the most common reason for pre-school children to visit a doctor, be prescribed antimicrobials, or undergo surgery. Recent Cochrane reviews of clinical trials have identified that antibiotics and grommet surgery are only moderately effective in treating OM, with recurrent or persistent infection observed in one third of children. My team is harnessing host-microbe interactions to develop therapies to improve OM treatment and prevention. This includes development of a novel intranasal therapy that will soon be entering first-in-human trials. We are also leading a randomised controlled trial of a novel approach to disrupt middle ear biofilm that permits antibiotics to work more effectively in children with recurrent or chronic OM. This presentation will provide an update on our work on these novel OM therapies, which have the potential to improve health outcomes for children in Australia and worldwide.