Rapid Comprehensive Identification of Pneumonia Pathogens

描述(申请人提供)：下呼吸道感染(LRTI)，包括肺炎，是对人类健康的重大威胁。例如，社区获得性肺炎和流感是美国第七大主要死亡原因。引起肺炎的病原体种类繁多。然而，定义肺炎的致病微生物是复杂的。标准的基于培养的方法速度慢，成品率低，因此通常不进行测试。在个体患者层面上，缺乏病因诊断可能导致经验性和长期使用广谱抗生素或缺乏有效的治疗。在人群一级，缺乏基于病原体的诊断降低了以下能力：a)准确评估疾病负担，b)评估免疫等干预措施的效果，c)追踪抗菌素耐药性，d)研究新的治疗药物。对患者样本进行快速和全面的分析将极大地有助于肺炎的诊断。爱达荷州技术公司(ITI)基于集成的聚合酶链式反应和检测技术生产快速诊断产品。FilmArray平台是一个完全集成的自动化系统，可在一小时内完成样品准备和目标识别。FilmArray具有使用方便、结果产生时间短和高度多样化的病原体面板，特别适合于肺炎病毒和细菌的评估。我们建议在疑似肺炎患者的样本上测试两个FilmArray面板，针对呼吸道病原体和败血症引起的细菌。选择合适的呼吸道采集地点是一个复杂的问题，将通过分析成人和儿童患者的几种临床样本类型来解决(具体目标1)。当检测到不止一种病原体时，使用量化方法可能有助于理解病原体的相对贡献(具体目标2)。在本项目结束时，我们将选择信息量最大的站点 样本类型朝着开发一种全面的诊断测试迈进，该测试有可能显著改善肺炎患者的护理。 公共卫生相关性：在诊断肺炎方面面临的挑战包括已知的可引起下呼吸道感染的大量病毒和细菌，以及培养确认缓慢和不敏感。爱达荷州科技公司的FilmArray平台是一个完全集成的自动化系统，可以在一小时内完成病毒和细菌病原体的样本准备和鉴定。针对呼吸道病毒和导致败血症的细菌的现有FilmArray面板将进行修改，以开发一种全面的测试来识别肺炎病原体。

DESCRIPTION (provided by applicant): Lower respiratory tract infections (LRTI), including pneumonia, are a significant threat to human health. For example, community-acquired pneumonia and influenza are together the seventh leading cause of death in the United States. There is a wide range of pathogens that can cause pneumonia. Defining the causative organism in pneumonia, however, is complex. Standard culture-based methods are slow and low-yield, therefore testing is often not performed. At the level of the individual patient, lack of an etioloic diagnosis can lead to the empiric and prolonged use of broad-spectrum antibiotics or to lack of effective therapy. At the population level, lack of a pathogen-based diagnosis decreases the ability to: a) accurately assess disease burden, b) evaluate the effects of interventions such as immunization, c) track antimicrobial resistance and d) investigate new therapeutic agents. Diagnosis of pneumonia would be greatly aided by rapid and comprehensive analysis of patient samples. Idaho Technology Inc. (ITI) manufactures rapid diagnostic products based on integrated PCR and detection technologies. The FilmArray platform is a fully-integrated automated system that performs sample preparation and target identification in one hour. The FilmArray, with its ease-of-use, short time-to-result and highly multiplexed pathogen panels is uniquely suited to the evaluation of both viral and bacterial agents of pneumonia. We propose to test two FilmArray panels, targeting respiratory pathogens and sepsis causing bacteria, on samples from patients with suspected pneumonia. Appropriate choice of site for respiratory collection is a complex question that will be addressed through analysis of several clinical sample types from both adult and pediatric patients (Specific Aim 1). The use of quantification may be beneficial in understanding the relative contribution of pathogens when more than one is detected (Specific Aim 2). At the end of this project, we will choose the most informative site and sample type to move forward toward development of a comprehensive diagnostic test with the potential to significantly improve the care of patients with pneumonia. PUBLIC HEALTH RELEVANCE: Challenges in diagnosing pneumonia include the large number of viruses and bacteria known to cause lower respiratory tract infections and slow and insensitive confirmation by culture. Idaho Technology's FilmArray platform is a fully-integrated automated system that performs sample preparation and identification of viral and bacterial pathogens in one hour. Existing FilmArray panels directed toward respiratory viruses and sepsis- causing bacteria will be modified to develop a comprehensive test to identify pneumonia pathogens.