Antimicrobial Endotracheal Tube to Combat Biofilm

ABSTRACT Ventilator associated pneumonia VAP is one of the most costly and deadly nosocomial infections Over cases of VAP occur per year resulting in over deaths and a cumulative annual cost to the US Healthcare system over Billion Endotracheal tubes ETT are inserted into the trachea to allow mechanical ventilation They are a critical part of the ventilator circuit but also provide a conduit for transmission of bacteria to the lungs Biofilms form rapidly on ETTs and are thought to play a key role in VAP development as well as the antibiotic resistance and persistence commonly seen with VAP The goal of this project is to develop an innovative antimicrobial endotracheal tube ETT that is effective against biofilm producing pathogens associated with VAP The proposed ETT will be coated with a novel polymer formulation of an engineered cationic antimicrobial peptide eCAP previously shown to be effective against drug resistant bacteria common to VAP The polymer coating will provide controlled eCAP release and protection of the peptide until release It will also will provide a hydrophilic biocompatible interface resistant to fouling The scope of work covers development of the coating formulation and application to ETTs with an evaluation of coating stability and ETT cuff compliance eCAP release rates and stability in artificial saliva will be measured by RP HPLC Feasibility will be demonstrated using Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus which are two of the most common causative organisms in VAP The plan includes studies designed to show prevention of biofilm formation on coated ETTs The plan also employs an in vitro model that is designed to evaluate the roles that both ETT balloon compliance and bactericidal effect play in preventing bacteria transfer from the throat to the lungs Finally cytotoxicity against tracheal epithelial cells will be assessed If successful the product is expected to have a significant and sustained impact on reducing morbidity and mortality associated with VAP PROJECT NARRATIVE Ventilator associated pneumonia is one of the most costly and deadly nosocomial infections resulting in over lost lives per year in the US The objective of this work is to develop an innovative antimicrobial endotracheal tube ETT that is effective against biofilm producing pathogens associated with VAP The product is expected to reduce morbidity mortality and excess costs associated with VAP