SBIR-STTR Award

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.

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is to improve the clinical outcomes and quality of life for patients suffering from complicated urinary tract infections (cUTI). Today, cUTIs account for 400,000 hospitalizations annually in the United States. Unfortunately, multidrug resistant pathogens are a common cause of cUTI. Many are resistant to the first-line antibiotic (Ceftriaxone), which is used as the empiric treatment of this condition. However, the high incidence of multidrug resistant pathogens causing cUTI delays the time until patients receive more appropriate treatment. Delayed time to appropriate therapy in cUTI has been attributed to extended hospital stays and an increased risk of morbidity and mortality. The current standard test for diagnosing a drug-resistant cUTI takes 2-3 days from obtaining a patient sample. Therefore, diagnostic tests that can rapidly inform the initial treatment of UTIs are urgently needed to improve patient care.This Small Business Innovation Research (SBIR) Phase II project aims to develop a rapid urinary diagnostic test that will enable the detection of ceftriaxone-resistant uropathogens. Early detection of resistance to first-line therapies would enable antibiotic prescribing to be informed, reducing the risk of disease progression in patients. In the case of UTIs, disease progression can lead to severely invasive infections, predominately sepsis. Therefore, diagnostics that can detect resistance to first-line antibiotics enable early treatment interventions, reducing the time to appropriate treatment and reducing the risk of disease progression. Decreased treatment time also lowers the healthcare costs associated with drug-resistant cUTI, as disease progression is associated with increased lengths of hospital stays compared to susceptible infections. The completion of the Phase II project will yield the development of a prototype test that can provide actionable information regarding ceftriaxone susceptibility in less than 5 minutes. This project?s success will provide clinicians with a diagnostic solution for cUTIs that can be acted on immediately to improve patient outcomes and aid antibiotic stewardship by preventing the unnecessary use of inappropriate antibiotics.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.