Rapid sensitive low cost test for resistant microbes causing hospital infections

针对引起医院感染的耐药微生物进行快速、灵敏、低成本的检测

• 批准号: 7540215
• 负责人: SADANAND GITE
• 金额: $ 28.5万
• 依托单位: FIRST LIGHT DIAGNOSTICS , INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7540215
• 关键词: Admission activity; Antibiotic Resistance; Antibiotics; Awareness; Bacteria; Biological Assay; Blood; CD4 Positive T Lymphocytes; Cell Count; Cells; Cessation of life; Clinical; Clostridium difficile; Complex; Count; Data; Detection; Food; Generations; Goals; Growth; HIV; Healthcare Systems; Hospitals; Hour; Image; Immunoassay; Individual; Infection; Infection Control; Mandatory Testing; Medical; Methods; Microbe; Molecular; Monitor; Nose; Nosocomial Infections; Nucleic Acid Amplification Tests; Nucleic Acids; Numbers; Patients; Performance; Phase; Population; Procedures; Proteins; Public Health; Range; Rate; Reagent; Reporting; Resistance; Sampling; Screening procedure; Site; Staphylococcus aureus; System; Technology; Testing; Today; Vancomycin resistant enterococcus; Whole Blood; Work; bacterial resistance; base; cost; cost effectiveness; day; design; digital imaging; drug discovery; improved; instrument; methicillin resistant Staphylococcus aureus; microbial; novel; particle; pathogen; pressure; prototype; soft tissue; user-friendly; wound

DESCRIPTION (provided by applicant): We propose to develop a novel testing platform to enable rapid, ultrasensitive, accurate, user-friendly, and cost-effective screening for the antibiotic resistant bacteria that frequently cause serious hospital acquired infections. Every year, nearly 100,000 deaths result from 2 million serious hospital acquired infections at an estimated cost of $30.5B. About 20,000 of these fatalities are caused by methicillin-resistant Staphylococcus aureus bacteria (MRSA). Both the rate of hospital acquired infections and the spread of MRSA have increased dramatically in the last 30 years. Many individuals now carry MRSA on their bodies, even when healthy. When MRSA carriers are hospitalized the resistant microbe can cause serious infections for the carrier and others in the hospital. Recent studies have shown that hospitals can substantially decrease the occurrence of hospital acquired infections by screening admitted patients for MRSA and then treating them using rigorous infection control procedures including isolation. Traditional microbiological methods for screening patients for MRSA are very slow, requiring several days, and are therefore incompatible with rapid identification and isolation of MRSA carriers. New rapid MRSA tests based on nucleic acid amplification are used for MRSA screening at some sites. However these tests are expensive, complex and thus not currently practical for large scale screening in most hospitals. We aim to develop a novel rapid, sensitive, and easy-to-use system for large scale cost-effective MRSA screening. The system's proprietary technology uses low-cost non-magnified digital imaging to count individual S. aureus cells specifically tagged with highly fluorescent particles. The test determines the initial number of S. aureus cells in the sample and the number of S aureus cells after incubation for several hours in antibiotic-containing selective media. Only if the sample contains MRSA, will there be a significant in- crease in S. aureus cell number in the presence of antibiotic. An advantage of this phenotypic growth-based approach over genotypic nucleic acid-based tests is that it can be applied to any type of microbe and any anti- biotic. The Specific Aims are to (1) develop S. aureus-specific particle reagents and the MRSA screening as- say method; (2) develop an automated prototype system including an imaging instrument and a reagent- containing cartridge; and (3) demonstrate assay performance and compare it to the culture and nucleic acid amplification reference methods using clinical samples. Achieving these Specific Aims should justify a Phase 2 project that will focus on extending the MRSA assay to other sample types (e.g., wound, soft tissue, blood), developing tests for other important agents that cause hospital acquired infection agents (e.g., vancomycin resistant Enterococcus, C. difficile), and developing a pre-commercial prototype instrument/consumable system for MRSA screening. Besides its value for detecting resistant microbes, the system has commercial potential for other important cellular detection applications including detecting virally infected cells, CD4+ cells (for monitoring HIV status), food pathogens, and in drug discovery. PUBLIC HEALTH RELEVANCE The commercialized MultiPath system for screening for resistant bacteria will help lower the rate of hospital acquired infections. The approximately 2 million hospital acquired infections that occur per year cause nearly 20,000 deaths and cost the healthcare system about $30B a year. The new system will enable more hospitals to implement rapid testing, which in turn leads to improved infection control and lower hospital acquired infection rates.

描述（由申请人提供）：我们建议开发一个新颖的测试平台，以使抗生素耐药细菌的快速，超敏，准确，用户友好和具有成本效益的筛查，经常引起严重的医院感染。每年，200万严重医院的感染造成了近100,000人死亡，估计费用为30.5B美元。这些死亡中约有20,000人是由金黄色葡萄球菌（MRSA）引起的。在过去的30年中，医院获得的感染率和MRSA的传播均大大增加。现在，即使在健康的情况下，许多人现在将MRSA携带在身体上。当MRSA载体住院时，抗性微生物可能会对载体和医院的其他人引起严重的感染。最近的研究表明，医院可以通过筛查接纳患者的MRSA，然后使用严格的感染控制程序（包括隔离）来治疗他们，从而大大减少医院获得感染的发生。筛查MRSA患者的传统微生物方法非常慢，需要几天，因此与快速鉴定和隔离MRSA载体不相容。基于核酸扩增的新快速MRSA测试用于某些部位的MRSA筛查。但是，这些测试是昂贵，复杂的，因此对于大多数医院的大规模筛查而言目前不实用。我们旨在开发一种新型的快速，敏感且易于使用的系统，用于大规模成本效益的MRSA筛选。该系统的专有技术使用低成本的非磁化数字成像来计算特异性标记具有高荧光颗粒的单个金黄色葡萄球菌。该测试确定样品中金黄色葡萄球菌细胞的初始数量和在含抗生素的选择培养基中孵育几个小时后的金黄色葡萄球菌细胞数量。只有在样品中包含MRSA时，在存在抗生素的情况下，金黄色葡萄球菌细胞的数量才会显着。基于基因型核酸的测试，这种基于表型生长的方法的一个优点是，它可以应用于任何类型的微生物和任何抗生物生物。具体目的是（1）开发金黄色葡萄球菌特异性粒子试剂和MRSA筛选方法； （2）开发一个自动原型系统，包括成像仪器和含有试剂的墨盒； （3）证明了测定性能并将其与使用临床样品的培养和核酸扩增参考方法进行比较。实现这些特定目标应证明一个第2阶段项目的合理性，该项目将集中于将MRSA测定法扩展到其他样本类型（例如伤口，软组织，血液，血液），并针对其他重要的药物开发了导致医院获得的感染剂的测试（例如，抗Vancomycin抗菌肠球菌，抗艰难杆菌，艰难C. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c.c。）除了检测抗性微生物的价值外，该系统还具有其他重要的细胞检测应用的商业潜力，包括检测病毒感染的细胞，CD4+细胞（用于监测HIV状态），食物病原体和药物发现中。公共卫生相关性的商业化多径系统用于筛查抗性细菌，将有助于降低医院获得的感染率。大约200万医院获得了每年发生的感染，造成近20​​,000人死亡，并使医疗体系造成约30B美元的损失。新系统将使更多的医院能够实施快速测试，从而导致感染控制和下医院获得的感染率得到改善。