Ventilator associated pneumonia (VAP) is one of the most costly and deadly nosocomial infections. Over 250,000 cases of VAP occur per year resulting in over 36,000 deaths and a cumulative annual cost to the US Healthcare system over 3 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.

Public Health Relevance

Ventilator associated pneumonia is one of the most costly and deadly nosocomial infections resulting in over 36,000 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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
3R43HL134456-01S1
Application #
9379817
Study Section
Program Officer
Reineck, Lora A
Project Start
2017-01-06
Project End
2017-03-31
Budget Start
2017-01-06
Budget End
2017-03-31
Support Year
1
Fiscal Year
2017
Total Cost
$50,000
Indirect Cost
Name
Allvivo Vascular, Inc.
Department
Type
Domestic for-Profits
DUNS #
179043893
City
Lake Forest
State
CA
Country
United States
Zip Code
92630