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: 8126683
• 负责人: SADANAND GITE
• 金额: $ 98.29万
• 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 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8126683
• 关键词: Admission activity; Antibiotic Resistance; Antibiotics; Awareness; Bacteria; Bacterial Counts; Biological Assay; Blood; Boxing; CD4 Positive T Lymphocytes; Cell Count; Cells; Cessation of life; Clinical; Clinical Sensitivity; Clinical Trials; Clostridium difficile; Complex; Country; Detection; Disease; Disease Marker; Epidemic; Food; Future; Geographic state; Goals; Growth; HIV; Health; Healthcare; Hereditary Disease; Hospitals; Hour; Incidence; Individual; Infection; Infection Control; Infectious Agent; Label; Life; Marketing; Measures; Medical; Methods; Microbe; Monitor; Nose; Nosocomial Infections; Patients; Performance; Phase; Preparation; Procedures; Reagent; Reporting; Resistance; Sampling; Screening procedure; Specificity; Staphylococcus aureus; Swab; System; Technology; Test Result; Testing; Time; Toxin; Vancomycin resistant enterococcus; Virus; Work; base; cost; cost effective; design; digital imaging; drug discovery; methicillin resistant Staphylococcus aureus; novel; pathogen; pressure; prototype; soft tissue; user-friendly; wound

DESCRIPTION (provided by applicant): We propose to develop a novel automated platform to enable rapid, sensitive, user-friendly, and cost-effective screening for the antibiotic resistant bacteria that frequently cause serious healthcare associated infections. Every year, about 100,000 deaths result from 2 million serious healthcare associated infections at an estimated cost of $35B. About 20,000 fatalities are caused by the bacterium methicillin-resistant Staphylococcus aureus (MRSA). Many healthy individuals are colonized with MRSA. When these MRSA carriers are hospitalized, the resistant microbe can cause serious infections for the carrier and others in the hospital. Several recent studies have shown that hospitals can significantly decrease the number of healthcare associated infections by using rapid tests to screen admitted patients for MRSA colonization and then treating the colonized patient with rigorous infection control procedures. New rapid MRSA tests based on PCR are fast, but are either too expensive or too complex to be implemented in most hospitals. Traditional microbiological methods for screening patients for MRSA are inexpensive but are too slow (1-2 days) to most effectively lower infection rates. We recently completed a Phase I project demonstrating the feasibility of a novel, rapid, simple, and cost-effective method for MRSA screening that should for the first time allow any hospital to implement rapid testing for infection control. The platform technology uses low-cost non-magnified digital imaging to rapidly count individual fluorescently labeled S. aureus cells. The test determines whether a patient's sample contains MRSA by testing for S. aureus cells that can grow in antibiotic-containing media during a brief incubation. The rapid (3.3 hr) Phase I MRSA test's analytical sensitivity is comparable to PCR tests (10 CFU/sample). When applied to clinical nasal samples (n=163), the test showed high clinical sensitivity (95%) and specificity (98%) comparable to the on-market PCR tests. We also designed, developed, and integrated a fully functional automated bench top analyzer prototype and developed and manufactured a low-cost consumable prototype for the MultiPath MRSA test. Here we propose to build on our Phase I work to develop a prototype automated platform and MRSA test cartridge that can be used in subsequent Phase III beta field trials. Specifically we aim to (1) further decrease time to results and develop optimized stable reagents; (2) develop a low-cost MultiPath MRSA/SA test cartridge; (3) develop a low-cost automated beta MultiPath analyzer; (4) integrate and verify the platform functionality; and (5) demonstrate the performance of the MultiPath MRSA/S. aureus (MRSA/SA) test. Achieving these Specific Aims will enable subsequent Phase III beta field testing that will in turn support a future regulatory submission. The MultiPath platform will also be able to accommodate a broad menu of tests for agents that cause healthcare associated infections (e.g., vancomycin resistant Enterococcus and C. difficile), infectious viruses, food pathogens, toxins, molecular disease markers, and drug discovery targets.

描述（由申请人提供）：我们建议开发一个新型的自动化平台，以使抗生素耐药细菌的快速，敏感，用户友好且具有成本效益的筛查经常引起严重的医疗保健相关感染。每年，约有100,000人死亡是由200万严重的医疗保健相关感染造成的，估计成本为35B美元。大约20,000人死亡是由金黄色葡萄球菌（MRSA）抗甲氧西林细菌引起的。许多健康的个体被MRSA殖民。当这些MRSA携带者住院时，耐药的微生物会对载体和医院的其他人引起严重的感染。最近的几项研究表明，通过使用快速测试来筛查招生的患者MRSA定植，然后使用严格的感染控制程序治疗殖民的患者，医院可以大大减少与医疗保健相关的感染的数量。基于PCR的新快速MRSA测试很快，但是太昂贵或太复杂而无法在大多数医院中实施。用于筛查MRSA的患者的传统微生物方法很便宜，但太慢（1-2天），无法有效地降低感染率。我们最近完成了一个I期项目，证明了一种新颖，快速，简单且具有成本效益的MRSA筛查方法的可行性，该方法应该首次允许任何医院实施快速的感染控制测试。该平台技术使用低成本的非磁化数字成像来快速计算单个荧光标记的金黄色葡萄球菌。该测试确定了患者的样品是否通过测试在短暂孵育期间可以在含抗生素培养基中生长的金黄色葡萄球菌细胞来含有MRSA。快速（3.3 hr）I期MRSA测试的分析灵敏度与PCR测试相当（10 CFU/样品）。当应用于临床鼻样品（n = 163）时，该测试显示出与市场PCR检验相当的临床敏感性（95％）和特异性（98％）。我们还设计，开发和集成了功能齐全的自动化台式Analyzer原型，并为多径MRSA测试开发和制造了低成本的可消耗原型。在这里，我们建议在我们的阶段I努力建立开发一个原型自动化平台和MRSA测试盒，可用于随后的III阶段Beta现场试验。具体而言，我们的目标是（1）进一步减少结果并开发优化的稳定试剂； （2）开发低成本多径MRSA/SA测试弹药筒； （3）开发低成本的自动β多径分析仪； （4）集成和验证平台功能； （5）演示多径MRSA/s的性能。金黄色（MRSA/SA）测试。实现这些特定目标将使随后的III期Beta现场测试反过来支持未来的监管提交。多径平台还将能够适应引起医疗保健相关感染的药物（例如，抗性霉素肠球菌和艰难梭菌），感染性病毒，食物病原体，毒素，分子疾病标记物和药物发现靶标的广泛测试。