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

项目总结 该项目名为《通过快速浓缩、鉴定和表型抗生素药敏试验进行诊断》 来自血液的病原体，根据RFA-AI-17-014提交，用于开发临床有用的伙伴关系 抗菌素耐药性细菌的诊断(R01)“将开发一种快速、灵敏和特异的诊断方法 独立于培养的鉴定和测定抗菌药敏感性和/或的平台 细菌病原体的抗药性。滥用和误用抗生素导致了一场迫在眉睫的 全球卫生危机：广泛的抗生素耐药性的发展。血液感染(BSI)是 其临床影响尤为显著：严重脓毒症患者超过100万人 每年，这些人中有15%到30%的人死亡。在缺乏快速和可靠的 抗生素敏感性测试(AST)，卫生保健提供者通常求助于广谱抗生素，进一步 不断升级的耐药菌株的发展。遏制抗生素耐药性的出现和传播 微生物和提供适当的救生治疗需要护理点(POC)诊断，可以 直接从临床样本中快速测定病原体的药物敏感性，消除了冗长的 目前需要微生物生长的程序。 该项目解决了对快速诊断的关键需求，这种快速诊断可以识别和确定 微生物病原菌耐药谱。为了解决这个问题，我们建议开发一种 结合高度创新的技术，以(1)直接从 没有培养步骤的血液；(2)展示了浓缩技术与快速和 病原菌的特异性多重检测；(3)验证增菌与创新的兼容性， 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 不到2小时，直接从人血中提取。这一多学科的项目将由一个高度 经验丰富的产业研究团队，拥有杰出的学术和临床合作者，并将创造一个 直接从临床样本诊断和治疗血流感染的新范式-- 无忧无虑。无数人的生命将被拯救，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.