Rapid Immunodiagnosis of Drug-Resistant Bacterial Pathogens

项目总结/摘要 该提案描述了快速免疫测定试剂盒的第二阶段开发， β-内酰胺类抗生素耐药性的测定，用作床旁检测 尿路感染的诊断测试。今天，用于UTI的抗生素处方 根据经验，临床医生没有可用的诊断方法来避免治疗耐药 病原体对药物有抗药性。这个问题 导致抗药性日益普遍，使许多药物无法使用。 拟议的检测试剂盒将是一个侧流免疫测定，类似于家庭的原则， 验孕棒试验设计基于β- 内酰胺酶，赋予对β-内酰胺抗生素抗性的酶。在第一阶段， 申请人开发了一种能够区分β-内酰胺耐药 β-内酰胺敏感分离株的细菌。在第二阶段，该试验将转换为 一个简单的20分钟的测试套件，和一个完整的可制造的产品将被开发出来。 将进行临床验证研究，以确定 该产品.在第二阶段的成功结束时，我们希望展示一个快速， 简单，准确的测试β-内酰胺耐药性的UTI，使临床医生能够测试 未处理的尿液样本，并根据结果确定最佳抗生素。 这种能力有望彻底改变细菌性UTI的管理， 临床医生能够选择性地处方较旧的β-内酰胺抗生素，以检测阴性 患者对疗效有很高的信心。这样的待遇有望得到改善 结果为患者，同时大大减少经验性使用广谱 抗生素

PROJECT SUMMARY/ABSTRACT This proposal describes Phase II of the development of a rapid immunoassay test kit for the determination of β-lactam antibiotic resistance, to be used as a point-of-care diagnostic test for urinary tract infections. Today, antibiotics for UTI are prescribed empirically, with no diagnostics available to clinicians to avoid treating resistant infections with the very drug to which the pathogens are resistant. This problem has resulted in ever-increasing prevalence of resistance, rendering many drugs unusable. The proposed test kit will be a lateral flow immunoassay, similar in principle to a home pregnancy test. The test design is based on monoclonal antibodies specific for β- lactamases, the enzymes conferring resistance to β-lactam antibiotics. In Phase I, the applicant developed a working assay capable of distinguishing β-lactam-resistant bacteria from β-lactam-sensitive isolates. In Phase II, this assay will be converted into a simple 20-minute test kit, and a complete manufacturable product will be developed. Clinical validation studies will be carried out to determine the real-world performance of the product. At the successful conclusion of Phase II, we expect to demonstrate a rapid, simple, and accurate test for β-lactam resistance in UTI, enabling clinicians to test unprocessed urine samples and determine the optimal antibiotics based on the results. This capability promises to revolutionize the management of bacterial UTIs, giving clinicians the ability to selectively prescribe older β-lactam antibiotics to test-neagtive patients with a high confidence of efficacy. Such treatment is expected to improve outcomes for patients while dramatically reducing the empiric use of broad-spectrum antibiotics.