An automated, scalable, and rapid AST system for Gonorrhea STIs

用于淋病性传播感染的自动化、可扩展且快速的 AST 系统

• 批准号: 10327731
• 负责人: Roy R Swiger
• 金额: $ 96.73万
• 依托单位: ACENXION BIOSYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-15 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10327731
• 关键词: Agar; Agreement; Anatomy; Antibiotic Therapy; Antibiotic susceptibility; Antibiotics; Antimicrobial Resistance; Bacteria; Behavior; Carbon Dioxide; Categories; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Research; Code; Computer software; Computers; Contracts; Data; Data Analyses; Development; Devices; Ensure; Environment; Feedback; Funding; Future; Genetic Materials; Genitourinary system; Gonorrhea; Growth; Healthcare; Hospitals; Hour; Human; Human Resources; Incidence; Intermediate resistance; Investments; Laboratories; Liquid substance; Location; Manuals; Methods; Microfluidics; Minimum Inhibitory Concentration measurement; Molecular; Monitor; Neisseria gonorrhoeae; Optics; Organism; Patients; Phase; Phenotype; Predisposition; Preparation; Price; Protocols documentation; Public Health; Reader; Reading; Recording of previous events; Reporting; Reproducibility; Sampling; Savings; Sensitivity and Specificity; Sexually Transmitted Diseases; Single-Blind Study; Small Business Innovation Research Grant; Speed; Spottings; Surveillance Program; Surveys; System; Testing; Time; Work; base; co-infection; commercialization; cost; design; experimental study; field study; hospital laboratories; instrument; laboratory facility; practical application; programs; prototype; resistance mechanism; response; success

Gonorrhea is a sexually transmitted infection (STI) caused by the bacterium Neisseria gonorrhoeae (NG) that infects the urogenital, anorectal and pharyngeal tracts in humans. In 2018, there were an estimated 1.14M cases in the US, and 86.9M cases worldwide. Of concern is the growing incidence of antimicrobial resistance not only due to inappropriate use of antibiotics, but also because NG interacts with and acquires genetic material from other co-infections in the anatomical sites that it infects. This wide range of resistance mechanisms that NG isolates can potentially harbor makes it very challenging to develop rapid molecular methods of Antibiotic Susceptibility Testing (AST). Even among phenotypic AST methods, it has so far not been considered feasible to perform automated broth microdilution based ASTs on NG: principally because it is a fastidious organism in liquid culture. As a result, the primary method used to perform ASTs for NG is the manual agar dilution method, which (because it is so labor intensive) is currently conducted in only a very limited number of public health labs. Even these labs test only 200-300 samples a month. Acenxion Biosystems proposes to develop the first fully automated NG phenotypic AST platform that both satisfies the current CDC guidance for surveillance and fulfils an unmet clinical need for AST-guided “directed” antibiotic therapy. Our instrument will provide Minimum Inhibitory Concentration (MIC) and Susceptible/ Intermediate /Resistance (S/I/R) interpretation in < 6 hours with minimal sample preparation (<5 min per sample) at a reasonable price. The instrument will consist of stackable, cassette reader units with up to eight microfluidic cassette capacity; software/PC Controller; and single-use consumable (50-well microfluidic cassette pre-spotted with candidate antibiotics). Optimized broth and rapid stirring are employed for NG growth, enabling automated broth microdilution. With prior funding from the CDC, we have demonstrated proof-of-concept for the proposed instrument by building a partly-automated system to perform broth micro- dilution experiments on a single 16-well cassette, and used it monitor the growth (or lack thereof) of 3 NG strains (1 ATTC QC strain, and 2 AR isolate strains) in the presence of multiple candidate antibiotics with 100% sensitivity & specificity. We seek “Direct to Phase II” funds to expand this earlier work: build a fully automated instrument and test it against the CDC’s challenge AR bank panel of 50 clinical isolates (which span multiple resistance mechanisms and yield wide range of phenotypic responses). We chose this set of organisms in lieu of patient samples from 2 - 3 locations to ensure better chances of success in the real world. Our commercialization strategy aims to first bring efficiencies to the existing market (regional labs participating in the Gonococcal Isolate Survey Program) and then to expand the user (customer) base to hospital labs, clinical laboratory networks and clinical labs by enabling AST-guided directed antibiotic therapy for gonorrhea.

淋病是由细菌淋病（NG）引起的性传播感染（STI） 感染人类的​​泌尿生殖器，厌食和咽部。在2018年，估计有114万 美国的案件和全球869万例案件。令人担忧的是抗菌素抗性的日益增长的事件 不仅是由于不适当使用抗生素，而且还因为NG与通用互动并获得了通用 来自其感染的解剖部位中其他共同感染的材料。这种广泛的阻力 NG分离株可能会产生的机制使发展快速分子变得非常挑战 抗生素敏感性测试的方法（AST）。即使在表型AST方法中，它还没有 被认为可以可行，可以基于Ng的AST进行自动肉汤微稀释：主要是因为它 是液体培养物中的一种挑剔的生物。结果，用于执行NG AST的主要方法是 手动琼脂稀释法，该方法（因为它是如此强大的劳动密集型）目前仅在非常非常 数量有限的公共卫生实验室。即使这些实验室也仅测试每月200-300个样品。 Acenxion Biosystems提出的提案，以开发第一个完全自动化的NG表型AST平台 满足当前的CDC监视指南，并满足对AST指导“定向”的未满足的临床需求 抗生素疗法。我们的仪器将提供最小抑制浓度（MIC）和易感性/ <6小时的样品制备<6小时的中等/电阻（S/I/R）解释（每次<5分钟） 样本）以合理的价格。该仪器将由可堆叠的，盒式读取器单元组成，最多八个 微流体盒式容量；软件/PC控制器；和一次性消耗（50孔微流体 预先发现候选抗生素的盒式磁带）。优化的肉汤和快速搅拌用于NG 生长，实现自动肉汤微稀释。在疾病预防控制中心的先前资金中，我们已经证明了 通过构建部分自动化系统来执行肉汤微型 - 在单个16孔盒上进行稀释实验，并使用它监测3 ng的生长（或缺乏） 在存在多种候选抗生素的情况下，菌株（1个ATTC QC菌株和2个AR分离株） 100％灵敏度和特异性。我们寻求“直接到第二阶段”资金来扩展这项较早的工作：完全建立一个 自动化仪器并针对CDC的挑战AR银行面板进行测试，该面板由50个临床分离株（跨度 多种电阻机制并产生广泛的表型反应）。我们选择这套 代替来自2-3个位置的患者样本的生物，以确保在现实世界中获得成功的机会。 我们的商业化策略旨在首先为现有市场带来效率（参与的区域实验室 在淋球菌分离株调查计划中），然后将用户（客户）基础扩展到医院实验室， 临床实验室网络和临床实验室通过实现AST引导的淋病抗生素治疗。