SBIR Phase II: Rapid Assessment of Antibiotic Resistance by Mass Measurement

This Small Business Innovation Research Phase I project proposes to develop a "close-to-care" instrument that can assess antibiotic susceptibility of infection-causing bacteria in less than one hour. MEMS-fabricated sensors and integrated fluidics will measure the mass and growth rate of a small number of bacteria in-vitro with a resolution near 1 femtogram. By exposing the bacteria to a panel of antibiotics while monitoring growth rate, an infection's susceptibility profile will be determined very rapidly. Using this information, doctors will be able to select targeted antibiotic treatment much faster than is possible using conventional methods that require incubation and take 24 hours or longer - a crucial time savings. The platform will be validated on multiple E. coli strains that have a range of susceptibility, in both saline and healthy urine matrices. To demonstrate clinical value, the results will be compared to conventional methods. Additional tests will be performed on clinical isolates of E. coli and K. pneumoniae that cause urinary tract infections, and on MRSA (methicillin-resistant Staphylococcus aureus). The broader impact/commercial potential of this project will be to improve medical outcomes of infection and to facilitate antibiotic stewardship. The rapidly expanding prevalence of resistant bacteria, combined with a decline in the discovery of new antibiotics, pose one of today's most dire health threats. More than 100,000 people die of infections each year in the U.S., behind only cancer and heart disease. There is unanimous consensus among infectious disease experts that rapid diagnostics to identify resistance are crucial for administering targeted antibiotic therapy, leading to better outcomes, and for minimizing the spread of resistant strains. The test to be developed here directly addresses these needs. The project targets UTI (urinary tract infections) that are responsible for the majority of hospital-acquired infections; and MRSA (methicillin-resistant Staphylococcus aureus) that kills more than 20,000 Americans every year. The platform will be configured for "close-to-care" use in microbiology labs found in most hospitals, and capture a significant fraction of the $500M U.S. market for susceptibility testing equipment and reagents. The platform also will address nearer-term markets in antibiotic discovery and laboratory research.