PA21259, SBIR, Phase I, Development of a rapid, direct from blood, phenotypic antimicrobial susceptibility assay

项目总结 早期使用有效抗生素可显著改善与血流有关的临床结果 感染。然而，表型抗菌素敏感性试验(AST)需要选择正确的抗生素 在24-48小时培养之后花4-24小时(实际上通常更长)，这大大超过了窗口 在此期间，治疗必须开始避免死亡。唯一通过FDA批准的快速AST需要7个小时；然而， 它只能在培养后的单个患者样本上使用，而且对许多患者来说昂贵得令人望而却步 限制了它的广泛采用，并减少了其临床影响。因此，迫切需要一种可扩展的 和经济实惠的表型AST，可以直接快速获得微生物病原菌的耐药性图谱 从血液中培养，而不需要首先进行漫长的培养步骤。Aincobio正在开发一种新的表型AST，AST- Shift，即应用宏观和微观物理来开发微生物的生物物理特性来检测 病原体鉴定后一小时内对抗菌药的反应。AST-Shift设备将是一个 自动化、独立于文化、易于使用的台式仪器，将产生对 抗菌反应。它广泛适用于所有细菌和真菌病原体，是兼容的 下游应用，如继代培养或分子分析，占地面积小。这一阶段的目标是 证明Aincobio的AST测定法可以快速、准确地分析全血 报告多种病原体(革兰氏阴性、革兰氏阳性和 真菌)用针对细菌细胞壁的不同类别的抗菌药物(万古霉素和 美罗培南)、蛋白质合成(利奈唑胺，一种抑菌药物)、DNA合成(环丙沙星)和真菌细胞 壁(氟卡诺唑)和膜(米卡芬净)。第一阶段的成功完成将降低第二阶段项目的风险 专注于生产一次性多井测试设备，建立能够 在48个不同药物剂量通道中并行自动成像病原体，并关联AST-Shift结果 利用已建立的ESKAPE和其他常见病原体的CLSI临床断点来支持验证 在法规提交之前进行研究。通过减少确认感染的AST表型结果的时间，我们 将减少靶向治疗的时间，并有可能在以下情况下实现真正的变革性结果 结合未来独立于培养的快速病原体检测和身份识别技术。安科比奥很简单，成本很高- 有效的设备将为医生提供快速和可操作的数据，以支持靶向治疗和 提高抗菌药物管理力度。

PROJECT SUMMARY Early treatment with effective antibiotics significantly improves clinical outcomes associated with bloodstream infection. However, the phenotypic antimicrobial susceptibility tests (AST) required to choose the right antibiotics take 4-24 hours (often longer in practice) following a 24–48-hour culture, which significantly exceeds the window within which treatment must begin to avoid mortality. The only FDA-cleared rapid AST takes 7 hours; however, it can only be used on a single patient sample following culture and is prohibitively expensive for many institutions, limiting its broad adoption and reducing its clinical impact. Thus, there is an urgent need for a scalable and affordable phenotypic AST that can quickly obtain the drug-resistance profile for microbial pathogens directly from blood, without first requiring a long culturing step. Aincobio is developing a novel phenotypic AST, AST- Shift, that applies macro-and microscale physics to exploit the biophysical properties of microbes to detect response to antimicrobials within one hour following pathogen identification. The AST-Shift device will be an automated, culture-independent, easy-to-use benchtop instrument that will produce a quantitative analysis of antimicrobial response. It is broadly applicable to all bacterial and fungal pathogens, is compatible with downstream applications such as subculture or molecular analysis, and has a small footprint. This Phase I aims to demonstrate proof-of-concept that Aincobio’s AST assay can rapidly and accurately analyze whole blood samples to report on drug-resistance profiles for a number of pathogens (gram-negative, gram-positive, and fungi) treated with different classes of antimicrobial drugs that target bacterial cell walls (vancomycin and meropenem), protein synthesis (linezolid, a bacteriostatic drug), DNA synthesis (ciprofloxacin), and fungal cell walls (flucanozale) and membrane (micafungin). Successful completion of Phase I will de-risk a Phase II project focused on producing single-use multi-well test devices, building a mechanical optical system capable of automatically imaging pathogens in 48 different drug dose channels in parallel, and correlating AST-Shift results with established CLSI clinical breakpoints of ESKAPE and other common pathogens to support a validation study prior to regulatory submission. By reducing the time to phenotypic AST results of confirmed infection we will reduce the time to targeted treatment, with the possibility of enabling truly transformative results when combined with future culture-independent rapid pathogen detection and ID technologies. Aincobio’s simple, cost- effective device will empower physicians with rapid and actionable data to support targeted treatment and improve antimicrobial stewardship efforts.