SBIR Phase I: Phage-amplified Identification and Antimicrobial Susceptibility Test

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project will be the development of new diagnostic tools that allow rapid, direct-from-specimen bloodstream infection testing in clinical settings. The new technological innovations proposed here will more quickly identify bacteria responsible for the vast majority of blood infections while providing vital phenotypic data on antibiotics and dosages effective for treating these infections. This will improve patient outcomes through faster diagnosis and more precise antibiotic selection while also helping to combat the growing incidence of multidrug-resistant infections by reducing broad prescription of these drugs, which is critical to efforts to preserve the usefulness of existing antibiotics. The proposed project will develop a new tests for direct-from-specimen identification (ID), antimicrobial susceptibility testing (AST) and minimum inhibitory drug concentration (MIC) determination against Escherichia coli in blood. A significant limitation with existing standards-of-care is time required for actionable results; current approaches require 18-72 hrs. Due to the time required, physicians must make empiric antimicrobial therapy decisions that often lead to negative patient outcomes. Genotypic approaches are limited because of the varied mechanisms utilized by bacteria to evolve resistance, which can lead to false-negative results. Mass spectrometry requires colony isolation and provides ID only. Other time-consuming tests are then required for AST and MIC. Rapid phenotypic approaches are needed. To solve these problems, bacteriophage mixtures will be used that are highly specific and have demonstrated overlapping host ranges from component phages, produce a measurable signal quickly, and are well-suited to a simple automatable 96-well plate immunoassay. Project objectives of are to: 1) develop a rapid ID and AST/MIC immunoassay using phage-specific antibodies, and 2) prove feasibility of direct-from-specimen testing in blood samples. Side-by-side comparison to the current standard-of-care diagnostic strategies will also be performed. Anticipated results include ID, AST, and quantitative MIC in less than 5 hours directly in blood. 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.