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.

项目摘要/摘要 该建议描述了开发快速免疫测定测试套件的第二阶段 乳酰胺抗生素耐药性的确定，用于护理点 尿路感染的诊断测试。 从经验上讲，没有诊断诊断可供临床医生来避免治疗抗药性 病原体具有抗性的药物的感染 导致阻力的普遍性不断增加，使许多药物无法使用。 支撑测试套件将是横向流量免疫测定，原则上类似于房屋 妊娠试验。 乳酸，赋予对β-内酰胺抗生素的抗性的酶。 申请人开发了一种能够区分β-内酰胺抗性的工作测定 β-内酰胺敏感性分离株的细菌在II期中将转换为 将开发简单的20分钟测试套件和完整的可制造产品。 将进行临床验证研究以确定现实世界的表现 在第二阶段的成功结论中，我们希望证明 对UTI中β-内酰胺抗性的简单，准确的测试，使临床医生能够测试 未加工的尿液样品并确定结果低下的最佳抗生素。 这种可脊椎动物有望彻底改变细菌UTI的管理，使 临床医生有选择性开处方较旧的β-内酰胺抗生素来测试结束的能力 疗效的置信度很高。 患者的结局，同时大幅度降低了广谱的经验用途 抗生素。