Rapid Point-of-Care Test to Detect Bacteriuria & Confirm Urinary Tract Infection

描述(由申请人提供)：本提案描述了用于直接测量菌尿作为尿路感染(UTIs)诊断的快速护理点检测试剂盒开发的第二阶段。虽然细菌尿达到105cfu/ml是尿路感染诊断的金标准，但在实践中，所需的尿液培养是不可行的，因为典型的结果延迟了2天。尿路感染的诊断得到了其他办公室尿检试纸的辅助，但研究表明，误诊率很高，因此过度使用抗生素。拟议的检测试剂盒将首次允许在10分钟内直接测量尿液中的细菌浓度，以便在最初的办公室就诊时及时诊断尿路感染。拟议的试剂盒将是一种侧向流动免疫分析，类似于家庭怀孕测试。在测试设计中，将使用多个抗细菌单抗(MAb)直接与尿样中的细菌细胞结合，产生目测/结果校准到~105cfu/ml。这些单抗将从公司现有的&GT；80种此类抗体中挑选出来。该测试使用了该公司专有的“夹心PLUS”格式，允许在一次测试中同时使用多种抗体，并从根本上缩短了开发时间。在第一阶段，申请人开发了一个概念验证原型，该原型被证明可以检测到目标水平为104-105cfu/ml的六种尿路致病细菌菌株。在第二阶段，检测试剂盒将进一步优化敏感性和特异性，使用范围更广的尿路致病菌株，测试程序将进一步改进和简化。将进行临床验证研究，以确定该产品的实际性能。在第二阶段成功结束后，检测试剂盒将准备好用于制造、FDA审查和营销。对最终用户来说，这项测试的估计成本为每次测试2.00-5.00美元，远远低于尿液培养的成本，与目前尿量棒的成本持平。 公共卫生相关性：尿路感染是医生就诊的最常见原因之一，在美国，每年就诊人数超过800万人次。尿路感染的金标准诊断方法，即尿液培养检测细菌，目前作为常规程序不可行，因为获得结果的时间延迟了2天。这项提议继续开发了一种简单、廉价、10分钟的尿液细菌“试纸”测试，使医生能够在患者首次就诊时准确诊断尿路感染。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.