This proposal describes Phase II of the development of a rapid point-of-care test kit for the direct measurement of bacteriuria as a diagnostic for urinary tract infections (UTIs). While bacteriuria at a level of 105 CFU/ml is the gold standard for UTI diagnosis, in practice the required urine culture is unfeasible due to the typical 2-day delay in obtaining results. UTI diagnosis is aided by other in-office urinalysis dipsticks, but studies have shown that there is a high rate of misdiagnosis and consequent overtreatment with antibiotics. The proposed test kit will allow, for the first time, a direct "dipstick" measurement of bacterial concentration in urine within 10 minutes, in time to aid diagnosis of UTI during the initial office visit. The proposed test kit will be a lateral flow immunoassay, similar to a home pregnancy test. In the test design, multiple anti-bacteria monoclonal antibodies (MAbs) will be used to directly bind to bacterial cells in a urine sample, producing a visual +/- result calibrated to ~105 CFU/ml. These MAbs will be selected from the Company's existing collection of >80 such antibodies. The test utilizes the Company's proprietary SandwichPLUS" format, which allows the simultaneous use of multiple antibodies in a single assay and radically shortens development time. In Phase I, the applicant developed a proof-of- concept prototype which was shown to detect six uropathogenic bacteria strains at the target level of 104 - 105 CFU/ml. In Phase II, the test kit will be further optimized for sensitivity and specificity using a much broader range of uropathogenic isolates, and test procedure will be further improved and simplified. Clinical validation studies will be carried out to determine the real-world performance of the product. At the successful conclusion of Phase II, the test kit will be ready for manufacturing, FDA review, and marketing. The estimated cost of the test to the end user will be $2.00 - $5.00 per test, far less than the cost of urine culture and in line with the cost of current urine dipsticks.
Urinary tract infections are some of the most common cause of physicians'office visits, accounting for over 8,000,000 visits per year in the US. The gold-standard diagnostic method for UTI, urine culture to detect bacteria, is not currently feasible as a routine procedure due to the 2-day delay in obtaining results. This proposal continues the development a simple, inexpensive, 10-minute dipstick test for bacteria in urine, to give physicians the ability to accurately diagnose UTI during the initial office visit by the patient.