Rapid phage-amplified immunoassay for phenotypic UTI diagnosis and antimicrobial susceptibility testing

Abstract/ Summary Urinary tract infections (UTIs) are among the most common infection type in the U.S resulting in an estimated 10.5 million UTI-related office visits, 2-3 million emergency department visits, and over 100,000 hospitalizations in the U.S. annually at a cost of at least $3.5 billion. Sixty percent of women will experience at least one acute UTI in their lifetime. 25-50% of women have multiple recurrent infections requiring repeated antibiotics. UTIs and increasing high-level antibiotic resistance are a serious threat to human health. Evidence gained over the past decade strongly suggests that the high incidence and recurrent nature of these infections and the frequent use of broad-spectrum antimicrobials to treat them is promoting the emergence of new multidrug resistant (MDR) UTI strains. One in three UTIs are now sulfamethoxazole/trimethoprim resistant (once the standard treatment). One in five are resistant to five or more antibiotics and some are now resistant to all available drugs. The ability to ID and assess antibiotic resistance rapidly is critically important to minimize the emergence of new MDR UTIs and to maximize the efficacy of currently available treatment options. Current UTI diagnostic approaches require time-consuming pre-analysis organism isolation and enrichment and do not provide the comprehensive AST and MIC data needed to meet this challenge. Indeed, the largest labor component of the clinical diagnostic laboratory is spent processing and diagnosing UTIs. New approaches are needed to improve our ability to perform rapid ID, AST and MIC in order meet diagnostic demands. Ideally, such a system would allow actionable, same-day, direct-from-specimen testing of multiple drugs without the need for bacterial isolation or cultivation. Cobio's PhAAST-MIC, successfully developed in SBIR Phase I for E. coli in urine, enables simultaneous phenotypic ID, AST, and MIC testing directly from urine specimens within 5 hours. No currently available diagnostic platform allows for this combination of simultaneous same-day results for all three data types. As envisioned, Phase II will expand PhAAST-MIC capabilities to include the other most prevalent MDR uropathogens-specifically Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus saprophyticus, Pseudomonas aeruginosa and Proteus mirabilis and develop a regulatory pathway for FDA 510(k) clearance. Data generated by the test will provide tailored antimicrobial therapy designed to reduce testing times and improve antibiotic stewardship and patient outcomes. Cobio's expert R&D staff will continue to team with physicians and antibiotic resistance experts at the University of Colorado and Children's Hospital Colorado.