Rapid Low Cost Phenotypic Antibiotic Susceptibility Testing.

快速低成本表型抗生素敏感性测试。

• 批准号: 9347745
• 负责人: PAUL RHODES
• 金额: $ 99.81万
• 依托单位: SPECIFIC DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-07 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9347745
• 关键词: Affect; Agitation; Algorithms; Antibiotic Resistance; Antibiotic susceptibility; Antibiotics; Blood; Blood specimen; CLIA certified; Centers for Disease Control and Prevention (U.S.); Cessation of life; Characteristics; Chemicals; Clinical; Clinical Protocols; Clinical Research; Computer software; Consultations; Cyclosporine; Data; Dependence; Dependency; Detection; Development; Engineering; Environment; Evaluation; Future; Goals; Gold; Growth; Guidelines; Hand; Healthcare; Healthcare Systems; Hour; Incubators; International; Laboratories; Length of Stay; Liquid substance; Measures; Methods; Minimum Inhibitory Concentration measurement; Morbidity - disease rate; National Institute of Allergy and Infectious Disease; Organism; Pathogenicity; Patients; Pattern; Performance; Phase; Phenotype; Pilot Projects; Preclinical Testing; Predictive Analytics; Predisposition; Preparation; Protocols documentation; Research; Research Design; Resistance; Sampling; Shock; Speed; System; Systems Development; Technology; Temperature; Testing; Time; Walking; cost; cost effective; disorder prevention; engineering design; image processing; instrument; mortality; pathogen; pathogenic bacteria; prototype; research clinical testing; response; seal; sensor; skills; software systems; targeted treatment

Project Summary Antibiotic resistance has recently emerged as a global threat for healthcare systems. An increasing number of pathogenic bacteria are acquiring antibiotic resistance, and new forms of resistance are continuously emerging with alarming speed across international boundaries.1 In the U. S. alone, the Center for Disease Control and Prevention (CDC) has estimated 2 million patients per year are directly affected by antibiotic-resistant pathogens, leading to more than 23,000 deaths.2 Providing rapid, definitive and cost effective antibiotic susceptibility testing (AST) will be of increasingly vital importance in controlling this burgeoning problem. While legacy methods generally require overnight culturing, the time-urgency of determining effective antibiotics has prompted a push for rapid AST that can perform in a few hours. Unfortunately, some of the newest rapid AST instruments are either not suited to multiplexing, or are an order of magnitude more costly than legacy methods, discouraging their widespread use. A rapid multiplexed AST platform that provides minimum inhibitory concentrations (MICs) within hours at comparable cost to current methods will enable rapid determination of effective targeted therapy, resulting in short hospital stays and fewer additional laboratory tests, and decreasing morbidity and mortality along with associated healthcare expenses. Specific Technologies has introduced and with NIAID support commercially developed a culture system that combines detection with organism ID.3, 4 Using a printed array of chemically responsive colorimetric indicators introduced into culture headspace, the species-specific pattern of volatiles emitted during growth produce a species-specific pattern, which we have shown to reduce detection time and enable Gram status and species ID to be determined hands-free during culture. Here, we present data showing that the use of this system can be extended to very rapidly, order 1 hour, ascertain phenotypic antibiotic susceptibility. The preliminary data demonstrate that introduction of antibiotic to positive blood culture prompts a susceptibility-dependent and antibiotic concentration-dependent shift in volatile sensor response within <60 minutes. Recognizing that a commercial AST instrument must be multi-well, we have performed pilot study in which the positive sample is removed from a blood culture bottle and divided into a multi-chamber setting, in which even at pilot study stage we demonstrate a < 2 ½ hrs phenotypic AST, measuring values matching the results of the CLIA-compliant Sensititre gold standard. Moreover, the disposable is inherently low cost, as it only depends upon an inexpensive printed sheet of CSA’s. Finally, not only is this method intrinsically low-cost but low-skill compatible, as there is no sample preparation from positive blood culture. It is thus very well-suited for both 24-hour/day developed world labs, where it will speed time-to-answer, as well as the low-skill environments of the developing world. In this direct-to-Phase II application, we propose to use our CSA technology to systematically quantify, and validate the parameter-dependence of this system and then engineer and produce a benchtop instrument suitable for preclinical and clinical testing, which will provide a low cost, highly automated multiplexed phenotypic susceptibility determination directly from a positive blood sample in less than 90 minutes. We propose to develop and commercialize an instrument that integrates our rapid AST capability with our Spec80 blood culture and species ID system that is being commercialized now, offering a uniquely streamlined and low cost system with by far the fastest yet proposed time from patient sample to detection, ID and phenotypic multiplexed quantitative AST.

项目摘要 抗生素耐药性最近成为医疗系统的全球威胁。越来越多 致病细菌的数量是抗生素耐药性，新形式的耐药性是 在国际边界之间不断出现，以惊人的速度出现。1仅在美国， 疾病控制与预防中心（CDC）估计每年有200万患者直接 受抗生素耐药性病原体的影响，导致23,000多人死亡。2迅速提供 确定且具有成本效益的抗生素敏感性测试（AST）将提高至关重要 在控制这个水牛问题时。虽然遗产方法通常需要一夜文化，但 确定有效抗生素的时间繁忙促使人们推动可以执行的快速AST 几个小时。不幸的是，一些最新的快速AST乐器不适合 多路复用，或者是比遗产方法更昂贵的数量级，使他们的 宽度使用。一个快速的多路复用AST平台，可提供最小的抑制浓度 （MIC）在数小时内以与当前方法的可比成本相当的成本将有效地确定有效 有针对性的治疗，导致住院时间短，额外的实验室测试较少，并且减少 发病率和死亡率以及相关的医疗费用。 特定的技术已经引入并随着NIAID支持在商业上开发了培养系统 将检测与有机体ID.3，4结合使用。 引入培养顶空的指标，这是在 生长会产生特定物种的模式，我们已证明它可以减少检测时间并启用 革兰氏状态和物种ID将在文化期间免提。在这里，我们提出显示的数据 该系统的使用可以迅速扩展到1小时，确定表型抗生素 敏感性。初步数据表明，将抗生素引入阳性血液培养 提示易感性依赖性和抗生素浓度依赖性挥发性传感器的转移 在<60分钟内的响应。认识到商业AST仪器必须是多孔，我们有 执行的试点研究，其中从血液培养瓶中取出阳性样品并分裂 进入多室环境，即使在试验研究阶段，我们也证明了<2½小时表型 AST，测量符合CLIA符合CLIA符合敏感金标准的结果的值。而且， 一次性固有的成本是低成本，因为它仅取决于CSA的廉价印刷纸。 最后，由于没有样本 从阳性的血液培养中制备。因此，它非常适合24小时/天发达的世界 实验室，它将加快发展时间的时间以及发展中国家的低技能环境。 在此直接到相之间的II应用中，我们建议使用我们的CSA技术系统地量化， 并验证该系统的参数依赖性，然后工程师并产生台式机 适用于临床前和临床测试的仪器，这将提供低成本，高度自动化 多重表型敏感性直接从阳性血液样本中确定不到90 分钟。我们建议开发和商业化一种融合我们快速AST的工具 我们的Spec80血液培养和物种ID系统的能力现在正在商业化，提供 一个独特的精简和低成本系统，到目前为止，患者样本中最快但拟议的时间 要检测，ID和表型多路复用定量​​AST。