Rapid detection of pathogens and antimicrobial susceptibility directly in patient samples

直接快速检测患者样本中的病原体和抗菌药物敏感性

• 批准号: 9207124
• 负责人: SADANAND GITE
• 金额: $ 87.93万
• 依托单位: FIRST LIGHT DIAGNOSTICS , INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-06 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9207124
• 关键词: Accidents; Acquired Immunodeficiency Syndrome; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antimicrobial susceptibility; Awareness; Biochemical; Biological Assay; Catheterization; Cell Count; Cells; Cessation of life; Data; Diagnostic; Diagnostic tests; Enzymes; Funding; Future; Gene Transfer; Genetic; Genetic Polymorphism; Genome; Growth; Health Care Costs; Healthcare; Healthcare Systems; Hospitals; Hour; Imaging technology; Infection; Life; Medical; Medical Economics; Methods; Microbiology; Nosocomial Infections; Nucleic Acid Amplification Tests; Pathogen detection; Patients; Performance; Predisposition; Preparation; Reagent; Resistance; Sampling; Sepsis; Severities; Severity of illness; Source; Staphylococcus aureus; Technology; Test Result; Testing; Time; Urinary tract infection; Urine; Work; antimicrobial; bacterial resistance; base; cost; cost effective; digital imaging; improved; killings; malignant breast neoplasm; manufacturing process; methicillin resistant Staphylococcus aureus; microbial; multi-drug resistant pathogen; novel; pathogen; prevent; public health relevance; rapid detection

 DESCRIPTION (provided by applicant): Hospital infections exact an enormous medical and economic toll, killing more people than AIDS, breast cancer, and auto accidents combined and costing the US healthcare system tens of billions of dollars annually. The emergence of pathogens resistant to all classes of antibiotics and the paucity of new antibiotics threaten to create vulnerability to infection reminiscent of the pre-antibiotic era. Rapid and accurate diagnostic testing enables timely implementation of the correct antimicrobial therapy which saves lives, decreases the severity of illness, improves antibiotic stewardship, and reduces healthcare costs. However, most testing today depends on slow 19th century microbiological culture methods which require days to get clinicians the answers they need to optimally treat their patients. Nucleic acid tests can be rapid but they are expensive and cannot reliably determine which antibiotics to use to treat most pathogens. Nucleic acid tests are limited by the often extensive genetic polymorphism of resistant bacteria due to their rapidly evolving genomes and facile inter-species gene transfer. We aim to develop the novel MultiPath platform to fill the technology gap, providing rapid, accurate, quantitative, and inexpensive identification and rapid antimicrobial susceptibility for panels of pathogens that cause the most important types of hospital infections. Because the method tests for growth in the presence of antibiotics, this rapid approach is robust to and unhindered by the genetic complexity of resistant pathogens. The simple and cost-effective digital imaging technology tests patient samples directly and eliminates sample preparation, cell-disruption, pipetting, biochemical purification, enzymes, and wash steps. Here we pro- pose to develop the first MultiPath panel tests for one of the most common hospital acquired infections, urinary tract infections, which can cause life-threatening blood infections. The project develops assays and consumable cartridges for a two stage UTI diagnostic approach that direct analyzes urine samples. First, the MultiPath UTI ID test will quantitatively detect 9 of the most common UTI pathogens in a rapid (15 min) and sensitive (<500 CFU/ml) assay. Then, if there is an infection, the pathogen in the patient's urine sample will be analyzed for susceptibility to a panel of relevant antibiotics in a rapid (3 hr) MultiPath UTI AST test. Specifically, we propose to (1) develop UTI target-specific MultiPath immunoreagents, (2) develop and demonstrate the multiplexed MultiPath UTI ID assay, (3) develop and demonstrate the performance of the MultiPath UTI ID cartridge, (4) develop and demonstrate the multiplexed MultiPath UTI AST assay, and (5) develop and demonstrate the MultiPath UTI AST cartridge. The successful project will deliver manufactured cartridge consumables with integrated stabilized reagents with performance data demonstrating the tests have the potential to meet rigorous regulatory specifications. Future work will refine and scale the consumable manufacturing processes and integrate the MultiPath UTI consumables with the high-throughput, on-demand, random-access, automated benchtop analyzer being developed with funding from other sources.

 描述（由适用提供）：医院感染是一种增强的医疗和经济损失，比艾滋病，乳腺癌和汽车事故造成的人数更多，使美国医疗保健系统每年数千亿美元。病原体对所有类别的抗生素具有抗药性的出现，而新抗生素的稀少有可能使感染脆弱性，让人联想到抗抗生素前时代。快速准确的诊断测试可以及时实施正确的抗菌治疗，从而挽救生命，降低疾病的严重程度，改善抗生素管理并降低医疗保健成本。但是，当今大多数测试取决于19世纪的慢速微生物培养方法，这些方法需要几天才能为临床医生提供最佳治疗患者所需的答案。核酸测试可能很快，但它们很昂贵，不能可靠地确定要使用哪种抗生素来治疗大多数病原体。核酸测试受到抗性细菌的遗传多态性的限制，由于其快速发展的基因组和易于体形间基因转移。我们旨在开发新颖的多路径平台来填补技术空白，提供快速，准确，定量和廉价的身份证 以及对导致医院感染最重要类型的病原体的快速抗菌敏感性。由于该方法在存在抗生素的情况下对生长进行了测试，因此这种快速方法对抗性病原体的遗传复杂性具有牢固性和不受欢迎。简单且具有成本效益的数字成像技术直接测试患者样品，并消除样品制备，细胞干扰，移液，生化纯化，酶和洗涤步骤。在这里，我们将prosos开发第一个多径面板测试，用于最常见的医院感染之一，尿路感染，这可能导致威胁生命的血液感染。该项目为两级UTI诊断方法开发了测定和易消耗筒，该方法可以直接分析尿液样品。首先，多径UTI ID测试将在快速（15分钟）和敏感（<500 cfu/ml）测定中定量检测9个最常见的UTI病原体。然后，如果有感染，将分析患者尿液样本中的病原体在快速（3小时）多径AST测试中对一组相关抗生素的敏感性。具体而言，我们建议（1）开发UTI特定的多径免疫反应，（2）开发和演示多路复用的UTI ID分析，（3）开发并证明了多径UTI ID墨盒的性能，（4）开发和演示多路复用AST uti AST分析和（5）开发和（5）开发和演示倍增AST CARTRIDGE。成功的项目将提供制造的墨盒消耗品，并具有稳定的试剂，并具有性能数据，表明测试有可能满足严格的监管规格。未来的工作将完善和扩展可消耗性的制造过程，并将多路athUTI消耗品与高通量，按需，随机访问，自动化台式分析仪与其他来源的资金一起开发。