PA21259, SBIR, Phase I, Development of a rapid, direct from blood, phenotypic antimicrobial susceptibility assay

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PROJECT SUMMARY Early treatment with effective antibiotics significantly improves clinical outcomes associated with bloodstream infection. However, the phenotypic antimicrobial susceptibility tests (AST) required to choose the right antibiotics take 4-24 hours (often longer in practice) following a 24–48-hour culture, which significantly exceeds the window within which treatment must begin to avoid mortality. The only FDA-cleared rapid AST takes 7 hours; however, it can only be used on a single patient sample following culture and is prohibitively expensive for many institutions, limiting its broad adoption and reducing its clinical impact. Thus, there is an urgent need for a scalable and affordable phenotypic AST that can quickly obtain the drug-resistance profile for microbial pathogens directly from blood, without first requiring a long culturing step. Aincobio is developing a novel phenotypic AST, AST- Shift, that applies macro-and microscale physics to exploit the biophysical properties of microbes to detect response to antimicrobials within one hour following pathogen identification. The AST-Shift device will be an automated, culture-independent, easy-to-use benchtop instrument that will produce a quantitative analysis of antimicrobial response. It is broadly applicable to all bacterial and fungal pathogens, is compatible with downstream applications such as subculture or molecular analysis, and has a small footprint. This Phase I aims to demonstrate proof-of-concept that Aincobio’s AST assay can rapidly and accurately analyze whole blood samples to report on drug-resistance profiles for a number of pathogens (gram-negative, gram-positive, and fungi) treated with different classes of antimicrobial drugs that target bacterial cell walls (vancomycin and meropenem), protein synthesis (linezolid, a bacteriostatic drug), DNA synthesis (ciprofloxacin), and fungal cell walls (flucanozale) and membrane (micafungin). Successful completion of Phase I will de-risk a Phase II project focused on producing single-use multi-well test devices, building a mechanical optical system capable of automatically imaging pathogens in 48 different drug dose channels in parallel, and correlating AST-Shift results with established CLSI clinical breakpoints of ESKAPE and other common pathogens to support a validation study prior to regulatory submission. By reducing the time to phenotypic AST results of confirmed infection we will reduce the time to targeted treatment, with the possibility of enabling truly transformative results when combined with future culture-independent rapid pathogen detection and ID technologies. Aincobio’s simple, cost- effective device will empower physicians with rapid and actionable data to support targeted treatment and improve antimicrobial stewardship efforts.