Direct detection and identification of antimicrobial resistance genes in bloodstream infections - PROJECT SUMMARY Leading to over 270,000 deaths in the US annually, septicemia is the systemic inflammatory response to a bloodstream infection (BSI). Timely diagnosis and treatment of BSIs has been demonstrated to improve patient outcomes and reduce hospitalization time. However, currently accepted diagnostic approaches still require primary blood cultures, which are not only slow, requiring ~1-3 days, but also demonstrate reduced sensitivity in the presence of antimicrobial treatment. There is thus a significant need for new diagnostic approaches that do not require cultures and provide faster, more accurate results. To address this unmet need, HelixBind developed RaPID (Resistance and Pathogen IDentification), a fully automated, sample-to-answer platform appropriate for placement throughout the hospital. RaPID consists of a bench-top Analyzer operating single-use cassettes capable of identifying and characterizing complex invasive infections directly from patient specimens, without cultures. Being culture-free, RaPID tests are not inhibited by polymicrobial infections nor prior antimicrobial treatment. The first test implemented on this platform, RaPID/BSI, incorporates a broad test menu of 21 bacterial and fungal pathogens with single CFUs/ml sensitivity within roughly 3 hours. Over multiple clinical studies the test has demonstrated >94% sensitivity and >99% specificity relative to culture across the test menu. Owing to the product’s advantages over exiting alternatives and its potential to improve care, the FDA designated RaPID/BSI a Breakthrough Technology in 2020. HelixBind has recently completed proof-of-concept studies of a reflex test to complement RaPID/BSI which targets the most common and clinically relevant antimicrobial resistance genes found in BSIs. This test, RaPID/R, has not only demonstrated single CFUs/ml sensitivity across the panel of resistance genes, but also the ability to properly characterize multiple drug resistant (MDR) microorganisms. A manual version of the has been used to successfully detect resistance in clinical samples. In this proposed Phase II project, HelixBind will translate the test to the automated RaPID platform. Studies demonstrating analytical sensitivity and specificity will be completed as will a blinded clinical assessment of RaPID/R. These studies will ensure that product performance matches specifications and clinical requirements. In parallel, study designs for product verification and validation will be completed and submitted to the FDA as part of a Pre-Submission process. To succeed in this project, we have assembled an accomplished team with expertise in assay development, instrumentation, consumables manufacturing, regulatory compliance, clinical microbiology, and infectious disease. This team has a successful track record of commercializing FDA-cleared IVD platforms and assays. Together, we will build upon our preliminary work to complete product development. Upon completion of this project, we will be well placed to initiate formal Analytical and Clinical studies required for FDA clearance.
