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

PA21259，SBIR，第一阶段，开发快速、直接来自血液的表型抗菌药物敏感性测定

• 批准号: 10602780
• 负责人: Lorenzo Damico
• 金额: $ 30.65万
• 依托单位: AINCOBIO LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2024-08-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10602780
• 关键词: PA21259; SBIR; Phase; Development; rapid

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.

项目概要 早期使用有效抗生素治疗可显着改善与血液相关的临床结果 感染。然而，选择正确的抗生素需要进行表型抗菌药物敏感性试验 (AST) 24-48 小时培养后需要 4-24 小时（实际上通常更长），这明显超过了窗口 必须在此期间开始治疗以避免死亡。唯一获得 FDA 批准的快速 AST 需要 7 小时；然而， 它只能用于培养后的单个患者样本，并且对于许多人来说价格昂贵。 机构，限制了其广泛采用并降低了其临床影响。因此，迫切需要一种可扩展的 以及经济实惠的表型 AST，可以直接快速获得微生物病原体的耐药谱 从血液中提取，无需首先进行长时间的培养步骤。 Aincobio 正在开发一种新型表型 AST，AST- Shift，应用宏观和微观物理学来利用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物做出反应。 AST-Shift 设备将是 自动化、独立于培养物、易于使用的台式仪器，可对以下物质进行定量分析 抗菌反应。它广泛适用于所有细菌和真菌病原体，与 下游应用，如传代培养或分子分析，并且占地面积小。第一阶段的目标 证明 Aincobio 的 AST 检测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，抑菌药）、DNA合成（环丙沙星）、真菌细胞 壁（氟康唑）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孔测试装置，构建能够 自动并行对 48 个不同药物剂量通道中的病原体进行成像，并关联 AST-Shift 结果 已建立 ESKAPE 和其他常见病原体的 CLSI 临床断点来支持验证 在监管提交之前进行研究。通过缩短确诊感染的表型 AST 结果的时间，我们 将减少针对性治疗的时间，并有可能在以下情况下实现真正变革性的结果： 与未来独立于培养的快速病原体检测和 ID 技术相结合。 Aincobio 简单、成本低 有效的设备将为医生提供快速且可操作的数据，以支持有针对性的治疗和 改善抗菌药物管理工作。