SBIR-STTR Award

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project would establish a rapid, sensitive pathogen typing and antibiotic sensitivity test for Bloodstream Infections (BSI) that could help guide early antibiotic therapy. Timely and accurate diagnosis of BSI would decrease the incidence of sepsis, as well as unnecessary or inappropriate antibiotic administration that can contribute to pathogen mutation and antimicrobial resistance (AMR). The risk of unnecessary or under-prescribed antibiotics during the COVID-19 pandemic has intensified future AMR threats, especially given that the incidence of bacterial sepsis occurs in 1 out of 7 COVID-19 inpatients, with a 50% mortality rate. Thus, a rapid, reliable in vitro diagnostic test for BSI would improve patient outcomes and have a measurable impact on quality of care, infection control, and overall healthcare management.The proposed technology for blood stream infection (BSI) detection and antibiotic susceptibility testing (AST) is rapid, highly sensitivity, and requires a low specimen volume. The assay would provide advantages over current standards of care (blood culture; BC), which typically require 24 to 72-hours to confirm the presence of a BSI. Additionally, this novel BSI assay does not require complex amplification steps (polymerase chain reaction; PCR) to detect pathogens. Given sepsis mortality rates increase by 7.6% per hour without appropriate antibiotic administration, septic patient care and survival demands early screening innovations that quickly and easily type species and determine AST to guide responsible antibiotic administration. The delayed results associated with current BSI testing methods hinders effective antibiotic selection, accuracy and timing. The proposed technology is comprised of a patent-pending bloodborne pathogen enrichment innovation that combines functionalized magnetic beads and the unique Limulus Amebocyte Lysate (LAL) substrate. The assay is built on three principles: (1) LAL contains highly sensitive proteins capable of detecting cell wall markers on gram-negative bacteria and fungi; (2) Differential LAL blocking would distinguish fungal and bacterial infection; and (3) Inclusion of a silkworm larvae plasma would provide a colorimetric output that detects gram-positive bacteria.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

The broader impact of this Small Business Innovation Research (SBIR) Phase II project seeks to develop an improved era of infectious disease management, allowing rapid intervention for antibiotic therapy to stem the 30% mortality rate and associated cost impact of sepsis. With some 49 million cases worldwide and a 25-30% mortality rate, sepsis claims 11 million lives annually. Sepsis cases have been increasing 8.7% per year. To address the full spectrum of infectious diseases, innovations must deliver simple and affordable testing capabilities similar to routine hospital admission blood analyses. The proposed antifungal and antibacterial susceptibility test for the detection and treatment of bloodstream infections could benefit patients by improving patient management and hospital logistics. Sepsis is the most expensive healthcare challenge, with an estimated financial impact of more than $62 billion per year. This bloodstream infection screening assay could impact the entire continuum of care ? from initial hospital interactions through patient care and discharge ? by identifying infections early, optimizing treatment, and increasing survival. Direct customer survey-based estimates and independent information sources project a U.S. commercial opportunity of 226 million annual assays (36 million hospital admissions, 40 million intensive care patients, 130 million emergency walk-ins, and 20 million presurgical evaluations). The proposed project could result in the development of a user-friendly and affordable analytical tool for early detection of bloodstream infections that differentiates bacterial and fungal pathogens associated with sepsis and determine their antibiotic sensitivity in hours. Sepsis is a major public health and economic concern that results in one human death every 2.8 seconds. If bloodstream infections go undetected or untreated, patients can quickly escalate into sepsis or septic shock with mortality chances increasing by 8% per hour without appropriate antibiotic administration. Rapid and accurate detection of a bloodstream infections prior to the onset of sepsis is critical to limit the extent of tissue and organ damage, mortality, and associated hospital costs. The proposed innovation includes the use of an FDA-approved reagent called Limulus Amebocyte Lysate for clinical bloodstream infections and antifungal antibacterial susceptibility testing to guide therapeutic interventions, and routine surveillance of high-risk patient populations. The technical approach for this Phase II encompasses proficiency studies that would validate high-throughput detection of pathogens, as well as their antimicrobial sensitivity and resistance profiles in clinical blood specimens. Additionally, assay miniaturization and automation would be performed and are considered critical for future in vitro diagnostic partnership adoption.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.