Diagnostics for Sepsis and Community-Acquired Pneumonia

败血症和社区获得性肺炎的诊断

• 批准号: 6999467
• 负责人: WILLIAM G WEISBURG
• 金额: $ 46.49万
• 依托单位: NANOGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6999467
• 关键词: bacterial DNA; bioengineering /biomedical engineering; biomarker; biomedical automation; biomedical equipment development; clinical biomedical equipment; clinical research; communicable disease diagnosis; consumable /disposable biomedical equipment; cooperative study; diagnosis design /evaluation; diagnostic tests; early diagnosis; human subject; microarray technology; miniature biomedical equipment; nucleic acid amplification techniques; nucleic acid hybridization; patient oriented research; pneumonia; septicemia; virus DNA

DESCRIPTION (provided by applicant): Identifying the etiological agent of sepsis or community-acquired pneumonia (CAP) greatly improves the clinician's ability to manage the patient. Even with all of the newly developed technologies of molecular diagnostics, there have been essentially no recent innovations in diagnostic testing for these significant and often life threatening diseases. Blood culture, microbial sugar utilization-based identification, and empirical chemotherapy have dominated diagnostics and patient management decisions for several years. Empirical treatment - often inappropriate - is partially responsible for the epidemic spread of multidrug resistant pathogens. Bacterial, fungal, and viral agents can all be concurrently detected and identified with nucleic acid amplification and hybridization methods. Innovative approaches to nucleic acid isolation from clinical samples, coupled with multiplex PCR amplification, and detection on electronic microarrays has the potential to significantly advance the ability of the clinician to correctly identify the underlying pathogen and manage the disease. This proposal describes a program to merge innovative, yet proven technology for sample preparation, high multiplex amplification, and detection and differentiation with biomarkers identifying at least 17 agents of CAP and sepsis with an automated system for the clinical microbiology laboratory. The investigators have all made significant contributions in commercializing new molecular diagnostic systems for detection and identification of pathogens in the areas of: respiratory viruses, blood banking, sexually transmitted disease, bioterrorism, CAP, and sepsis. The specific aims are: (1) Optimize a multiplex PCR system including bacterial and viral CAP and sepsis agent targets; (2) Select a suitable sample preparation chemistry; (3) Optimize the assay on electronic microarrays; (4) Develop self-contained modules for the three assay steps; (5) Integrate the modules into a prototype disposable, on a prototype instrument; (6) Develop processes and specifications for critical raw materials; and (7) Test the prototype integrated assay in a clinical study. At the completion of the research program, a number of useful tools will be available to improve molecular diagnostic methods for CAP and sepsis (and potentially other diseases), and a fully integrated automated assay that will be in the final stages of commercialization.

描述（由申请人提供）：识别败血症或社区获得性肺炎 (CAP) 的病因可极大提高临床医生管理患者的能力。即使有了所有新开发的分子诊断技术，针对这些重大且常常危及生命的疾病的诊断测试基本上没有最近的创新。多年来，血培养、基于微生物糖利用的鉴定和经验性化疗一直主导着诊断和患者管理决策。经验性治疗——通常是不恰当的——是多重耐药性流行病蔓延的部分原因 病原体。细菌、真菌和病毒病原体都可以通过核酸扩增和杂交方法同时检测和鉴定。从临床样本中分离核酸的创新方法，加上多重 PCR 扩增和电子微阵列检测，有可能显着提高临床医生正确识别潜在病原体和控制疾病的能力。该提案描述了一项计划，将用于样品制备、高多重扩增、检测和分化的创新且经过验证的技术与识别至少 17 种 CAP 和败血症病原体的生物标志物与临床微生物实验室的自动化系统相结合。研究人员在呼吸道病毒、血库、性传播疾病、生物恐怖主义、CAP 和败血症等领域的病原体检测和鉴定的新型分子诊断系统商业化方面做出了重大贡献。具体目标是： (1) 优化多重 PCR 系统，包括细菌和病毒 CAP 以及脓毒症药物靶点； (2) 选择合适的样品制备化学物质； (3) 优化电子微阵列检测方法； (4) 为三个分析步骤开发独立的模块； (5) 将模块集成到原型仪器上的一次性原型中； （六）制定关键原材料的工艺和规范； (7) 在临床研究中测试原型集成测定。研究计划完成后，将提供许多有用的工具来改进 CAP 和脓毒症（以及潜在的其他疾病）的分子诊断方法，并全面 集成的自动化检测将处于商业化的最后阶段。