SBIR Phase I: A Rapid, Sensitive Pathogen Typing and Antibiotic Sensitivity Test for Bloodstream Infections (COVID-19)

Kepley Biosystems Incorporated, Greensboro NC

Investigators

Abstract

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.