Rapid Immunodiagnosis of Drug-Resistant Bacterial Pathogens

耐药细菌病原体的快速免疫诊断

• 批准号: 9199051
• 负责人: MARK GEISBERG
• 金额: $ 99.46万
• 依托单位: SILVER LAKE RESEARCH CORPORATION
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-10 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9199051
• 关键词: Ampicillin; Antibiotic Resistance; Antibiotics; Antibodies; Bacteria; Bacterial Infections; Biological Assay; Clinical; Clinical Research; Collection; Consultations; Cyclophosphamide; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Drug resistance; Enzymes; Fluoroquinolones; Generations; Guidelines; Home environment; Immunoassay; Immunological Diagnosis; Infection; Lactamase; Lactams; Lateral; Long-Term Care; Low Prevalence; Monobactams; Monoclonal Antibodies; Patients; Performance; Pharmaceutical Preparations; Phase; Predisposition; Pregnancy Tests; Preparation; Prevalence; Probability; Reporting; Research Design; Resistance; Resistance profile; Resort; Sampling; Small Business Technology Transfer Research; Testing; Treatment Effectiveness; Urinary tract infection; Urine; Uropathogen; Work; antimicrobial; base; beta-Lactam Resistance; beta-Lactamase; beta-Lactams; blind; clinical practice; community-acquired UTI; design; effective therapy; improved outcome; pathogen; point of care; point-of-care diagnostics; population based; pre-clinical; research clinical testing; trait; validation studies

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.

项目概要/摘要 该提案描述了快速免疫检测试剂盒开发的第二阶段 β-内酰胺抗生素耐药性的测定，用作现场护理 尿路感染的诊断测试。今天，医生开出了治疗尿路感染的抗生素 根据经验，临床医生没有可用的诊断方法来避免治疗耐药性 病原体对其具有抗药性的药物引起的感染。这个问题有 导致耐药性不断增加，导致许多药物无法使用。 拟议的测试套件将是侧流免疫测定，原理上与家用测试相似 妊娠测试。该测试设计基于β-特异性单克隆抗体 内酰胺酶，这种酶赋予β-内酰胺抗生素耐药性。在第一阶段， 申请人开发了一种能够区分β-内酰胺耐药性的工作测定法 来自β-内酰胺敏感分离株的细菌。在第二阶段，该检测将转化为 简单的 20 分钟测试套件，以及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真实世界的性能 产品。在第二阶段成功结束时，我们期望展示快速、 简单、准确的尿路感染 β-内酰胺耐药性测试，使临床医生能够测试 未经处理的尿液样本，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尿路感染的管理， 临床医生能够选择性地为检测阴性的患者开出较旧的 β-内酰胺抗生素 患者对疗效有很高的信心。这样的待遇有望改善 显着减少广谱药物的经验使用 抗生素。