Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2016

Becoming unstuck – targeting bacterial persistence mechanisms in otitis media to improve treatments. (#90)

Ruth b Thornton 1 2 , S Jeffares 2 , S Vijayasekaran 1 2 3 , L Kirkham 1 2 , S Wiertsema 1 , H L Coates 1 , P C Richmond 1 2 3
  1. School of Paediatrics and Child Health, University of Western Australia, Perth, WA, Australia
  2. Telethon Kids Institute, Perth, WA, Australia
  3. Princess Margaret Hospital for Children, Perth, Western Australia, Australia

Introduction: Otitis media is the main reason that a child will visit their GP, be prescribed antibiotics or undergo surgery. Infection is usually bacterial, however 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. Bacteria can also manipulate the immune system to release neutrophilic DNA in the form of neutrophil extracellular traps. This host DNA increases the viscosity of the middle ear effusion and assists in bacterial persistence through the formation of biofilms. These persistence mechanisms represent targets for new 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, as such efficacy is 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 and the contribution of the host and microbe need to be fully understood if effective treatments and preventions are to be developed. Dornase alfa at the time of VTI represents a novel approach that may target underlying persistence mechanisms.