Endotracheal tubes are a common biomedical device in widespread use for anesthesiology and tracheostomy procedures and for long-term ventilation. However, 60-80% of these devices eventually become colonized by bacteria in the trachea after intubation, leading to lung-related nosocomial infections, associated high rates of mortality and an additional cost to American healthcare of approximately $1 billion annually. The objective of this proposal, Phase I through Phase II, is to reduce the incidence of endotracheal tube infection by coating the outer surface and interior lumen of the device with a polyurethane hydrogel containing broad-spectrum, polyclonal human IgG antibodies. At the time of the insertion or implantation the device, the hydrogel coating will permit the slow and sustained release of IgG from the device surfaces into the tracheal implant environment and surrounding mucosal area. The released IgG antibodies will bind to invading bacteria, targeting them for phagocytosis before they can propagate, destroy tissues and form protective biofilms. Additionally, the direct delivery of IgG to mucosal surfaces eliminates pathogenic bacteria and re-establishes normal flora. This technology allows direct, local delivery of IgG at lower concentrations than that required for intravenous immunogloublin (IVIG). Contemporary IgG contains a wide range of antibodies to current and evolving antibiotic resistant strains of bacteria and will complement current antibiotic therapy while overcoming the problem of antibiotic resistance. The particular aims of this Phase I feasibility study will determine, through in vitro studies, the composition of the IgG polyurethane hydrogel coating, the rate of release of IgG from the hydrogel, IgG bioactivity and the most efficacious composition of gel and antibodies against common pathogens and their antibiotic resistant strains. After obtaining and confirming Phase I proof of principal, efficacy and composition, Phase II aims will be centered on the development of a prototype IgG polyurethane hydrogel product for in vivo evaluation with a joint venture biomedical device partner.
An even modest decrease in endotracheal tube-associated infection will result in improved treatment for millions of patients and major cost- savings for the American healthcare industry.
