Diagnostics via Rapid Enrichment, Identification, and Phenotypic Antibiotic Susceptibility Testing of Pathogens from Blood.

项目摘要 本项目“通过快速富集、鉴定和表型抗生素敏感性测试进行诊断 根据RFA-AI-17-014“开发临床有用的 抗生素耐药细菌诊断（R 01）”将开发一种快速，灵敏，特异的诊断方法， 用于非培养物依赖性鉴定和确定抗菌药物敏感性的平台，和/或 细菌病原体的抗性。滥用和滥用抗生素已经导致了即将到来的 全球健康危机：广泛的抗生素耐药性的发展。血液感染（BSI） 就其临床影响而言尤其重要：严重脓毒症的发病率超过100万， 美国人每年死亡，其中15%到30%的人死亡。由于缺乏快速可靠的 抗生素敏感性试验（AST），卫生保健提供者往往诉诸广谱抗生素，进一步 加速抗药性菌株的发展。阻止抗生素耐药性的出现和传播 生物体和提供适当的挽救生命的治疗需要床旁（POC）诊断， 直接从临床样本中快速测量病原体的药物敏感性， 目前的程序需要微生物生长。 该项目解决了一个关键的未满足的需要，快速诊断，可以识别和确定 微生物病原体的抗微生物剂耐药性概况。为了解决这个问题，我们建议制定一个 高度创新的技术组合，以（1）直接从 （2）证明富集技术与快速和 病原体的特异性多重检测;（3）验证富集与创新的， 确定表型抗生素敏感性的数字方法;以及（4）证明整个工作流程 病原体浓度，鉴定和表型抗生素敏感性测试可以在 2小时内直接从人血中提取。这一多学科项目将由一个高度 经验丰富的工业研究团队与杰出的学术和临床合作者，并将创建一个 直接从临床样本中诊断和治疗血流感染的新范例- 护理。无数的生命将被拯救，抗生素耐药性的传播将被阻止。

PROJECT SUMMARY This project “Diagnostics via Rapid Enrichment, Identification, and Phenotypic Antibiotic Susceptibility Testing of Pathogens from Blood,” submitted under RFA-AI-17-014 “Partnerships for Development of Clinically Useful Diagnostics for Antimicrobial-Resistant Bacteria (R01)” will develop a rapid, sensitive, and specific diagnostic platform for the culture-independent identification and determination of antimicrobial susceptibility and/or resistance of bacterial pathogens. The indiscriminate use and misuse of antibiotics has led to an impending global health crisis: the development of widespread antibiotic resistance. Bloodstream infections (BSI) are particularly significant with respect to their clinical impact: Severe sepsis strikes more than one million Americans every year, and 15 to 30 percent of those people die. In the absence of a rapid and reliable antibiotic susceptibility test (AST), health care providers often resort to broad-spectrum antibiotics, further escalating the development of drug-resistant strains. Halting the emergence and spread of antibiotic resistant organisms and providing appropriate life-saving therapy requires point-of-care (POC) diagnostics that can rapidly measure the drug susceptibility of a pathogen directly from clinical samples, eliminating the lengthy current procedures that require microbial growth. This project addresses a critical unmet need for rapid diagnostics that can both identify and determine the antimicrobial resistance profile of microbial pathogens. To address this problem, we propose to develop a combination of highly innovative technologies to (1) concentrate viable, low-abundance pathogens directly from blood without a culture step; (2) demonstrate the compatibility of the enrichment technology with the rapid and specific multiplexed detection of pathogens; (3) validate the compatibility of enrichment with an innovative, digital method of determining phenotypic antibiotic susceptibility; and (4) demonstrate that the entire workflow of pathogen concentration, identification, and phenotypic antibiotic susceptibility testing can be achieved in under 2 hours directly from human blood. This multidisciplinary project will be carried out by a highly experienced industrial research team with outstanding academic and clinical collaborators, and will create a new paradigm in diagnosis and treatment of bloodstream infections directly from clinical samples at the point- of-care. Countless lives will be saved and the spread of antibiotic resistance will be halted.