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

描述（由申请方提供）：本提案描述了用于直接测量菌尿作为尿路感染（UTI）诊断的快速床旁检测试剂盒的II期开发。虽然105 CFU/ml水平的菌尿是UTI诊断的金标准，但在实践中，由于获得结果的典型2天延迟，所需的尿培养是不可行的。泌尿道感染的诊断是由其他在办公室尿分析试纸辅助，但研究表明，有一个误诊率高，随之而来的过度治疗抗生素。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，以及时帮助在初次就诊期间诊断UTI。拟定的检测试剂盒将是一种侧流免疫测定法，类似于家用妊娠试验。在试验设计中，将使用多种抗菌单克隆抗体（MAb）直接结合尿液样本中的细菌细胞，产生校准至约105 CFU/ml的目视+/-结果。这些单克隆抗体将从公司现有的>80种此类抗体的集合中选择。该测试采用了公司专有的“三明治PLUS”格式，该格式允许在一次检测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，申请人开发了一种概念验证原型，该原型显示出在104 - 105 CFU/ml的目标水平下检测六种尿路致病性细菌菌株。在第二阶段，将进一步优化检测试剂盒的灵敏度和特异性，使用更广泛的尿路致病性分离株，并进一步改进和简化检测程序。将进行临床确认研究，以确定产品的真实性能。在第二阶段的成功结束，检测试剂盒将准备生产，FDA审查和营销。最终用户的测试成本估计为每次测试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。 公共卫生相关性：尿路感染是医生办公室访问的一些最常见的原因，在美国每年超过8，000，000次访问。尿路感染的金标准诊断方法，尿培养检测细菌，由于获得结果的2天延迟，目前作为常规程序不可行。该提案继续开发一种简单，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UTI。

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.