Learning Objectives: Biofilms, intracellular infection and NET production all play a role in chronic and recurrent OM and need to be targeted if treatments are to be effective.
Introduction: Otitis media (OM) is a complex paediatric disease involving interactions between the child, their environment and the microbes that ultimately cause infection. While OM is mainly attributed to bacterial infections, antimicrobials have limited efficacy in treatment or prevention of chronic or recurrent disease. We have demonstrated that bacteria can evade antimicrobial treatments and the immune response both within biofilms and host cells. These bacteria appear to invade and proliferate within cells and may adopt a biofilm phenotype. Bacteria can also manipulate the immune response to release DNA from neutrophils in the form of neutrophil extracellular traps. This host DNA increases the viscosity of the middle ear effusion and assists in the formation of bacterial biofilms, permitting the persistence of infection. These persistence mechanisms represent targets for development of treatment or preventative strategies to combat chronic and recurrent OM.
Methods: Dornase alfa is a DNase used in treating cystic fibrosis and is able to digest the DNA in middle ear effusion in vitro. We have established a clinical trial to determine the safety and efficacy of Dornase alfa at the time of ventilation tube insertion (VTI) in children with OM to prevent complications following surgery and reduce the need for repeat surgery.
Results: The Dornase alfa trial is still blinded so efficacy has not yet been assessed, however direct installation into the middle ear at the time of VTI has been demonstrated to be safe.
Conclusions: Bacterial persistence mechanisms need to be fully characterised and understood if effective treatments and preventions are to be developed. Dornase alfa at the time of VTI represents a novel approach that may target the underlying persistence mechanisms.
