Rapid Immunodiagnosis of Drug-Resistant Bacterial Pathogens

项目摘要/摘要 本提案描述了快速免疫检测试剂盒开发的第二阶段。 β-内酰胺类抗生素耐药性的测定作为一种监护方法 尿路感染诊断试验。今天，治疗尿路感染的抗生素被开出。 从经验上讲，临床医生没有诊断方法来避免治疗耐药 感染病原体具有抗药性的药物。这个问题已经 导致耐药性不断增加，导致许多药物无法使用。 拟议的检测试剂盒将是一种横向流动免疫分析，原则上类似于家庭 验孕测试。该试验设计基于针对β的单抗- 内酰胺酶，引起对β-内酰胺类抗生素耐药的酶。在第一阶段， 申请人开发了一种能够区分β-内酰胺耐药的有效检测方法 来自β-内酰胺敏感菌株的细菌。在第二阶段，这一检测将转化为 简单的20分钟测试套件和一个完整的可制造产品将被开发出来。 将进行临床验证研究，以确定 产品。在第二阶段的成功结束后，我们预计将展示一种快速、 简单、准确的尿路感染β-内酰胺类耐药性检测，使临床医生能够检测 未处理的尿样，并根据结果确定最佳抗生素。 这一能力有望彻底改变细菌尿路感染的管理，从而 临床医生有能力有选择地开出较老的β-内酰胺类抗生素进行检测阴性 患者对疗效有很高的信心。这样的治疗有望得到改善 患者的结果，同时大幅减少广谱的经验性使用 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.