SBIR-STTR Award

Ventilator-associated pneumonia (VAP) is the most costly and second most common hospital-acquired infection (HAI), accounting for over 86% of hospital-acquired pneumonia (HAP). Some 300,000 HAP patients are treated annually in the U.S., at an estimated annual hospital cost of more than $1.5 billion. The current paradigm for preventing VAP has been to implement patient care bundle practices and to use endotracheal tube (ETT) technologies that reduce bacterial access to and colonization on the tube surfaces. However, these strategies do not offer sustained inhibition of bacterial biofilm that is associated with VAP;their limited duration of efficacy hampers their value-particularly for late-onset VAP, which is more often associated with drug-resistant microbial species. Additionally, use of antimicrobial agents leads to resistance patterns that make infections more difficult to treat. By coating the tube surface, the risk of infection is reduced;however, this strategy at best only delays the infection onset. There are currently no definitive methods to prevent late-onset VAP associated with multi-drug-resistant pathogens. Sharklet Technologies therefore proposes to develop a novel ETT design capable of sustained biofilm inhibition that does not rely on traditional antibiotic coatings. Preliminary studies have shown that micro-patterns on polymer surfaces can be designed to inhibit bacterial biofilm-with the Sharklet"" micro-pattern being the most effective. Therefore, the overall goal of this multi-phase SBIR project is to develop, validate, and commercialize the use of the biomimetic Sharklet microscopic pattern to inhibit bacterial biofilm formation on the ETT lumen, cuff, and outer surfaces without the use of antimicrobial agents. The Specific Aims for Phase I are to 1) optimize performance of the Sharklet micro-pattern, and 2) test the most effective Sharklet micro-patterns for inhibition of biofilm formation with clinical isolates of the most common VAP causative pathogens in a mucin-modified growth media over the course of 14 days. (Previous projects have already proven the feasibility of manufacturing tubes with the Sharklet pattern on the inner or outer surfaces.) A follow-on Phase II project will be designed to develop scaled-up manufacturing methods for ETTs with Sharklet-patterned inner, outer, and cuff surfaces and to further demonstrate efficacy with an in vivo animal model. Additionally, Phase II will offer an opportunity to investigate a possible added benefit of a Sharklet-patterned ETT-reduced occlusion due to enhanced surface energy, which will be studied in an in vitro mucus occlusion model. The Phase I and Phase II SBIR data will be essential in attracting and fully engaging the types of ""Phase III"" private-sector investors and/or strategic partners with whom we are already discussing this technology. Phase III commercialization efforts will therefore be focused on establishing partnerships with medical device partners and distributors-particularly those in the ETT markets.

Public Health Relevance:
Every patient who receives mechanical ventilation via an endotracheal tube (ETT) is at risk for developing ventilator-associated pneumonia (VAP)-the second most common hospital-acquired infection, which has a high mortality rate and results in medical costs of some $1.5 billion annually in the U.S. alone. Given that an effective solution to this problem has not been developed, particularly for late-onset VAP, Sharklet Technologies, Inc., proposes to pursue the needed advance in the state-of-the-art by incorporating its Sharklet"" microscopic pattern onto the ETT components to inhibit biofilm formation that leads to bacterial infections and to ultimately reduce the incidence of VAP. This multi-phase SBIR research effort is focused on developing/commercializing a Sharklet-patterned ETT that significantly augments current ETT designs with the goal of increasing patient welfare and safety while greatly reducing medical costs.

Thesaurus Terms:
Accounting;Address;Animal Model;Animal Models And Related Studies;Anti-Microbial Drug Resistance;Anti-Microbial Drug Resistant;Antibiotic Agents;Antibiotic Drugs;Antibiotics;Antimicrobial Drug Resistance;Antimicrobial Drug Resistant;Aspiration Of Middle Ear;Bacterial Antibiotic Resistance;Bacterial Infections;Biological Mimetics;Biomimetics;Cause Of Death;Clinical;Culture Media;Data;Death Rate;Development And Research;Device Designs;Drug Resistance, Microbial;Drug Resistance;Drug Resistant Bacterium;Ensure;Environment;Goals;Hospital Costs;Hospital Infections;Hospital Acquired Infection;In Vitro;Incidence;Infection;Intensive Care Units;Intubation;Lead;Mrsa;Marketing;Mechanical Ventilation;Medical;Medical Device;Methicillin Resistant S. Aureus;Methicillin Resistant Staphylococcus Aureus;Methods;Microbial Biofilms;Microscopic;Middle Ear Paracentesis;Miscellaneous Antibiotic;Modeling;Modification;Mortality;Mortality Vital Statistics;Mucins;Mucous Body Substance;Mucus;Mucus Glycoprotein;Multi-Drug Resistance;Multidrug Resistance;Multiple Drug Resistance;Multiple Drug Resistant;Myringostomy;Myringotomy;Nosocomial Infections;Nosocomial Pneumonia;P. Aeruginosa;P.Aeruginosa;Paracentesis Of Tympanum;Patient Care;Patient Care Delivery;Patients;Pattern;Pb Element;Performance;Phase;Pneumonia;Pneumonitis;Polymers;Prevention;Private Sector;Protocol;Protocols Documentation;Pseudomonas Aeruginosa;Pseudomonas Pyocyanea;Publishing;Pulmonary Inflammation;Qualifying;R &D;R&D;Relative;Relative (Related Person);Research;Resistance;Resistance To Multi-Drug;Resistance To Multidrug;Resistance To Multiple Drug;Resistance To Infection;Resistant To Multiple Drug;Resistant To Multi-Drug;Resistant To Multidrug;Risk;S. Aureus;S.Aureus;Sbir;Sbirs (R43/44);Safety;Simulate;Small Business Innovation Research;Small Business Innovation Research Grant;Social Welfare;Solutions;Staphylococcus Aureus;Surface;Technology;Testing;Time;Tracheostomy;Tracheostomy Procedure;Tube;Tympanocentesis;Tympanostomy;Tympanotomy;Ventilator;Work;Anti-Microbial;Anti-Microbial Agent;Anti-Microbial Drug;Antimicrobial;Antimicrobial Agent;Antimicrobial Drug;Bacterial Antibiotic Resistant;Bacterial Disease;Bacterial Resistance To Antibiotic;Biofilm;Biomedical Implant;Clinical Relevance;Clinically Relevant;Commercialization;Cost;Design;Designing;Drug Resistant;Drug Resistant Bacteria;Endotracheal;Growth Media;Heavy Metal Pb;Heavy Metal Lead;Hospital Acquired Pneumonia;Hospital Associated Pneumonia;Implant Device;Implantable Device;Improved;In Vivo;In Vivo Model;Indexing;Indwelling Device;Infection Resistance;Innovate;Innovation;Innovative;Institutional Infection;Manufacturing Scale-Up;Mechanical Respiratory Assist;Meetings;Methicillin Resistant Staphylococcus Aureus (Organism);Microbial Drug Resistant;Model Organism;Mucous;Multi-Drug Resistant;Multidrug Resistant;Next Generation;Novel;Pathogen;Pathogenic Bacteria;Patient Safety;Prevent;Preventing;Research And Development;Resistance To Drug;Resistant;Resistant To Drug;Welfare

Ventilator-associated pneumonia (VAP) is the most costly and second most common hospital-acquired infection (HAI), accounting for over 86% of hospital-acquired pneumonia (HAP). Some 300,000 HAP patients are treated annually in the U.S., at an estimated annual hospital cost of more than $1.5 billion. The current paradigm for preventing VAP has been to implement patient care bundle practices and to use antimicrobial agents that reduce bacterial colonization on the tube surfaces. However, these strategies have not demonstrated consistent efficacy or widespread adoption. A major concern is the use of antimicrobial agents that lead to resistance patterns that make infections more difficult to treat. Under this multi-phase SBIR project, Sharklet Technologies therefore proposes to advance the state-of-the-art in this key area by developing, validating, and commercializing a novel endotracheal tube (ETT) design that is capable of sustained biofilm inhibition and that does not rely on traditional antibiotic coatings. This novel technology is based upon the proven Sharket-patterned surface that has been developed successfully under previous SBIR funding. Phase I studies met and exceeded research goals to optimize the Sharklet pattern and to obtain at least 50% reduction (p<0.05) of bacterial biofilm coverage of P. aeruginosa and MRSA in conditions that exacerbated biofilm growth such as mucin-rich media and presence of sub-lethal concentrations of antibiotics. The overall goal of this multi-phase SBIR project is to further develop, validate, and commercialize the use of the biomimetic Sharklet microscopic pattern to inhibit bacterial biofilm formation on the ETT surfaces without the use of antimicrobial agents. The Specific Aims for Phase II are to 1) manufacture prototypes of the Sharklet micro-pattern for completion of regulatory verification and validation testing; 2) carry out an FDA-recognized in vitro ventilator-endotracheal- lung model to test Sharklet micro-patterned ETT prototypes for inhibition of colonization and biofilm formation with clinical isolates of the most common VAP causative pathogens; 3) demonstrate reduced microbial colonization, biofilm formation, and lumen occlusion in a sheep model; and 4) carry out a clinical pilot study in the Massachusetts General Hospital's Surgical ICU to demonstrate reduced ETT colonization, biofilm formation and lumen occlusion. We will also submit a 510(k) with all of the Phase II data to obtain a device-level claim. The Phase II project will be carried out by the expert interdisciplinary R&D team that completed the Phase I work and that has completed successful Phase I and Phase II SBIR projects for NIH previously. Post-Phase II commercialization will involve scaled-up manufacturing methods for ETTs with Sharklet-patterned inner, outer, and cuff surfaces. The Phase II SBIR data will be essential in attracting and fully engaging industry partners with whom we are already discussing this technology (see letters).

Public Health Relevance Statement:


Public Health Relevance:
Every patient who receives mechanical ventilation via an endotracheal tube (ETT) is at risk for developing ventilator-associated pneumonia (VAP)-the second most common hospital-acquired infection, which has a high mortality rate and results in medical costs of some $1.5 billion annually in the U.S. alone. Given that an effective solution to this problem will require ETT device alterations, Sharklet Technologies, Inc., proposes to pursue the needed advance in the state-of-the-art by incorporating its Sharklet" microscopic pattern onto the ETT surfaces to inhibit biofilm formation that leads to infection and to ultimately reduce the incidence of VAP. This multi-phase SBIR research effort is focused on developing/commercializing a Sharklet- patterned ETT that significantly augments current ETT designs with the goal of increasing patient welfare and safety while greatly reducing medical costs.

NIH Spending Category:
Antimicrobial Resistance; Assistive Technology; Bioengineering; Clinical Research; Emerging Infectious Diseases; Infectious Diseases; Lung; Patient Safety; Pneumonia; Pneumonia & Influenza

Project Terms:
Accounting; Achievement; Address; Adoption; Animal Model; Antibiotics; antimicrobial; antimicrobial drug; Area; Bacterial Antibiotic Resistance; base; biomaterial compatibility; Biomimetics; Cause of Death; Clinical; Clinical Research; clinically relevant; commercialization; Complex; cost; Cost Savings; Data; Death Rate; design; Development; Device Designs; Devices; drug resistant bacteria; endotracheal; Environmental air flow; Funding; General Hospitals; Goals; Growth; Hospital Costs; Hospitals; Hour; improved; In Vitro; in vivo; Incidence; industry partner; Infection; Intensive Care Units; Intubation; Lead; Letters; Lung; manufacturing process; manufacturing scale-up; Massachusetts; Mechanical ventilation; Medical; meetings; methicillin resistant Staphylococcus aureus (organism); Methods; microbial; Microbial Biofilms; microbial colonization; Microbiology; Microfluidics; Microscopic; Modeling; Modification; Molds; Mortality Vital Statistics; Mucins; new technology; next generation; Nosocomial Infections; Nosocomial pneumonia; novel; Outcome; pathogen; Patient Care; Patients; Pattern; Phase; phase 1 study; Physiological; Pilot Projects; Pneumonia; Polyurethanes; prevent; Procedures; prototype; Pseudomonas; Pseudomonas aeruginosa; public health relevance; Relative (related person); Research; research and development; Resistance; Resistance to infection; Risk; Safety; Sheep; Silicones; Silver; Small Business Innovation Research Grant; Social Welfare; Solutions; Staging; success; Suction; Surface; Surgical Intensive Care; Symptoms; Technology; Testing; Time; tool; trend; Tube; United States National Institutes of Health; Ventilator; verification and validation; Work