SBIR Phase I: Development of point-of-care diagnostics to direct the appropriate use of antibiotics for the treatment of high-risk urinary tract infections

This Small Business Innovation Research Phase I project will provide critical development of a rapid diagnostic test capable of delivering the antibiotic resistance profile of a sample collected from patients suspected of suffering from urinary tract infections (UTIs). In the US there are approximately 8 million UTIs, and an increasing number of are caused by drug-resistant bacteria that significantly complicate the treatment of these infections. In general, patients suffering from a drug resistant UTI take longer to receive appropriate treatment, resulting in a greater risk of disease progression and onset of secondary comorbidities. Diagnostic tests that can rapidly identify drug-resistant UTIs will have a strong and positive impact on the treatment of these infections. The proposed work aims to optimize and expand the diagnostic capacity of a first-generation diagnostic assay to create a fully comprehensive test that can detect a drug-resistant UTI in minutes. The proposed SBIR Phase I project will advance the development of a dual-enzyme trigger-enabled cascade technology (DETECT), developed to detect low-abundant beta-lactamases produced by uropathogens to hydrolyze beta-lactamase antibiotics, rendering them ineffective. The presence of beta-lactamase-producing uropathogens can greatly complicate clinical decision-making because these pathogens are regularly resistant to the first-line antibiotics considered for treatment of urinary tract infections (UTIs). DETECT, applied as a diagnostic system, holds the potential to significantly improve the care of UTIs because it enables rapid identification of beta-lactamase-producing uropathogens directly from urine samples. The clinical feasibility of the technology has been demonstrated previously using clinical urine samples, first targeting a subset of beta-lactamases known as CTX-Ms. The proposed work aims to tune and optimize the first-generation system to offer a comprehensive diagnostic test that can accurately identify all of the clinically important beta-lactamases. This technology provides a simple, low-tech, and cost-effective way to inform patient treatment without the need of processing, urine sedimentation or centrifugation, or sophisticated instrumentation. 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.