This project ?Diagnostics via Rapid Enrichment, Identification, and Phenotypic Antibiotic Susceptibility Testing of Pathogens from Blood,? submitted under RFA-AI-17-014 ?Partnerships for Development of Clinically Useful Diagnostics for Antimicrobial-Resistant Bacteria (R01)? will develop a rapid, sensitive, and specific diagnostic platform for the culture-independent identification and determination of antimicrobial susceptibility and/or resistance of bacterial pathogens. The indiscriminate use and misuse of antibiotics has led to an impending global health crisis: the development of widespread antibiotic resistance. Bloodstream infections (BSI) are particularly significant with respect to their clinical impact: Severe sepsis strikes more than one million Americans every year, and 15 to 30 percent of those people die. In the absence of a rapid and reliable antibiotic susceptibility test (AST), health care providers often resort to broad-spectrum antibiotics, further escalating the development of drug-resistant strains. Halting the emergence and spread of antibiotic resistant organisms and providing appropriate life-saving therapy requires point-of-care (POC) diagnostics that can rapidly measure the drug susceptibility of a pathogen directly from clinical samples, eliminating the lengthy current procedures that require microbial growth. This project addresses a critical unmet need for rapid diagnostics that can both identify and determine the antimicrobial resistance profile of microbial pathogens. To address this problem, we propose to develop a combination of highly innovative technologies to (1) concentrate viable, low-abundance pathogens directly from blood without a culture step; (2) demonstrate the compatibility of the enrichment technology with the rapid and specific multiplexed detection of pathogens; (3) validate the compatibility of enrichment with an innovative, digital method of determining phenotypic antibiotic susceptibility; and (4) demonstrate that the entire workflow of pathogen concentration, identification, and phenotypic antibiotic susceptibility testing can be achieved in under 2 hours directly from human blood. This multidisciplinary project will be carried out by a highly experienced industrial research team with outstanding academic and clinical collaborators, and will create a new paradigm in diagnosis and treatment of bloodstream infections directly from clinical samples at the point- of-care. Countless lives will be saved and the spread of antibiotic resistance will be halted.
Infections caused by antibiotic-resistant bacteria claim tens of thousands of lives and cause over $50B of economic burden in the US. Bloodstream infections are an especially urgent, life-threatening case that requires development of rapid diagnostic technologies. This project will develop and validate methodology for enriching pathogens directly from blood, identifying those pathogens, and determining their antibiotic susceptibility and resistance, all without the need for a time-consuming step of pathogen blood culture. !