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

描述（由申请人提供）：该提案描述了用于直接测量尿路细菌诊断（uti）的快速即时检测试剂盒的二期开发。虽然105 CFU/ml水平的细菌尿是尿路感染诊断的金标准，但在实践中，由于获得结果通常需要2天的延迟，所需的尿培养是不可行的。尿路感染的诊断是由其他办公室尿液分析试纸辅助，但研究表明，有很高的误诊率和随之而来的抗生素过度治疗。拟议的检测试剂盒将首次允许在10分钟内直接“试纸”测量尿液中的细菌浓度，及时帮助在初次就诊时诊断尿路感染。拟议的检测试剂盒将是一种侧流免疫测定法，类似于家庭妊娠试验。在测试设计中，多种抗细菌单克隆抗体（mab）将被用于直接结合尿液样本中的细菌细胞，产生视觉+/-结果校准到~105 CFU/ml。这些单克隆抗体将从公司现有的bbbb80抗体中选择。该测试采用了公司专有的SandwichPLUS格式，允许在一次检测中同时使用多种抗体，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，该原型被证明可以在104 - 105 CFU/ml的目标水平下检测六种尿路致病菌菌株。在二期试验中，将进一步优化检测试剂盒的敏感性和特异性，使用更广泛的尿路病原菌分离株，并进一步改进和简化检测程序。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，测试试剂盒将准备好生产，FDA审查和营销。最终用户每次检测的估计成本为2.00 - 5.00美元，远低于尿液培养的成本，与当前尿液试纸的成本一致。

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.