Project Summary/Abstract Urinary tract infections (UTIs) are the most common infection type in the U.S., with around 10.5 million infections per year equating to a cost of $3 billion. Of significant concern to the healthcare industry, the number of antibiotic resistant UTIs is increasing at an alarming rate while determining which drugs are effective remains a significant challenge. Current clinical approaches require 1-3 days or longer, forcing physicians to treat with broad-spectrum antimicrobials while tests are being performed. Cobio Diagnostics proposes herein to continue feasibility testing of our phage-based technology that provides ID, AST, and MIC direct-from- specimen and within 5 hours. Successful development and commercialization of this rapid diagnostic will reduce testing times, improve treatment, and reduce healthcare costs while conserving effective drugs. The severity of UTIs, approximately 90% of which are caused by E. coli, range from asymptomatic bacteriuria to pyelonephritis, which can result in complications including kidney failure and septicemia with significant long term affects or death. One in three UTIs are sulfamethoxazole/trimethoprim resistant (once the standard treatment). One in five are resistant to five or more antibiotics with a smaller number now resistant to all available drugs. Current UTI diagnostic approaches require time-consuming pre-analysis organism isolation and enrichment and do not provide comprehensive AST/MIC data. The ability to rapidly ID and assess antibiotic resistance is critical to addressing the emergence of MDR UTIs. Ideally, such a system would allow actionable same-day ID, AST and MIC direct-from-specimen for multiple drugs without the need for bacterial isolation or cultivation. Therefore, the overall goal of this multi-phase SBIR project is to leverage our strong preliminary data to develop, validate and commercialize PhAAST-MIC, Cobio Diagnostics' proprietary phage-amplified immunoassay, which is a rapid, multiplexed, phenotypic test for bacterial ID, AST and MIC directly in urine—and ultimately to gain FDA-clearance for the clinical UTI diagnostic routine. Cobio's expert R&D staff will team with physicians and antibiotic resistance experts at the University of Colorado and Children's Hospital of Colorado to pursue the Phase I Aims: 1) Develop and characterize unique anti-coliphage antibodies for incorporation into PhAAST prototypes, 2) Prove the feasibility of PhAAST-MIC E. coli ID, AST and MIC in urine and 3) Validate PhAAST-MIC direct-from-urine analysis of E. coli UTI specimens and isolates with comparison to standard-of-care diagnostic practices. Demonstrating rapid and accurate performance of our technology in representative MDR E. coli positive urine samples will establish the potential of our novel approach within the limited scope of a Phase I feasibility project, and will set the stage for a larger Phase II demonstration against other organisms associated with MDR UTIs such as Klebsiella pneumoniae and Enterococcus faecalis.

Project Narrative Urinary tract infections (UTIs) are the most common infection type in the U.S. and life-threatening antibiotic resistance in these infections is increasing at an alarming rate. Current UTI diagnostics rely on time- consuming pre-analysis organism isolation and enrichment requiring an average of one to three days and do not provide comprehensive AST/MIC data. The overall goal of this project is to address this by developing, validating, and commercializing PhAAST-MIC; Cobio Diagnostics' proprietary phage-amplified immunoassay for bacterial ID, AST and MIC directly in urine.