Point of Care Nucleic Acid Diagnostic Device for Quantifying Bacteremia

用于量化菌血症的护理点核酸诊断装置

• 批准号: 7487323
• 负责人: Jork N Nolling
• 金额: $ 36.86万
• 依托单位: IQUUM, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7487323
• 关键词: Accident and Emergency department; Accounting; Adam11 gene; Adsorption; Adverse effects; Affinity; Antibiotics; Bacteremia; Bacteria; Biological Assay; Blood; CCL22 gene; Caring; Cells; Clinical; Clinical Trials; Contracts; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Early treatment; Ensure; Environment; Escherichia coli; Figs - dietary; Genus staphylococcus; Gold; Guanosine Monophosphate; Hand; Health; Healthcare; Hour; Housing; In Vitro; Infection; Laboratories; Lectin; Life; Medicare; Methods; Nucleic Acid Amplification Tests; Nucleic Acids; Organism; Pathogen detection; Pathology; Patients; Phase; Physicians; Preparation; Production; RNA, Ribosomal, 16S; Rate; Reaction; Recording of previous events; Reporting; Research Contracts; Reverse Transcriptase Polymerase Chain Reaction; Ribosomal RNA; Sampling; Scanning; Sepsis; Solid; Standards of Weights and Measures; Staphylococcus aureus; Stream; Symptoms; System; Technology; Testing; Time; Training; Tube; United States; United States Food and Drug Administration; Upper arm; Validation; Variant; Whole Blood; Work; Yang; base; chlorambucil/dactinomycin/methotrexate protocol; cost; day; experience; mortality; pathogen; point of care; pre-clinical; programs; rRNA Genes

DESCRIPTION (provided by applicant): Positive blood culture results are available in only 34% of such severe sepsis cases and antibiotic selection is usually based on the patient's clinical history. In life threatening cases, treatment is initiated with broad spectrum antibiotics before culture results are obtained because initiating treatment in the first 48 hours can significantly lower mortality rates. IQuum has developed a lab-in-a-tube (Liat(tm)) Analyzer which can be used to detect blood stream infections within 1 hour of patient presentation at an emergency department. This technology enables minimally trained healthcare practitioners to perform a nucleic acid test using whole blood as the sample input. We propose to develop a reverse transcriptase polymerase chain reaction (RT-PCR) diagnostic assay for detecting the 16S ribosomal RNA. Because each cell contains 1,000 to 10,000 copies of rRNA the RT-PCR assay, the expected sensitivity of the device will allow for the detection of bacteremia titers of ~3 cells /10 ml of whole blood. We propose to use BUGS'n BEADS(tm) (Genpoint AS) or lectin coated filters for sample preparation; a method based on an initial adsorption of bacteria to a solid phase matrix with high affinity for bacteria. Alternatively, we will explore nucleic acid specific capture of bacterial rRNA. All of these sample preparation alternatives will be tested using the same diagnostic device. We further propose to obtain FDA approval for a multiplex assay as well as seek CLIA waived status for the device. We propose to file our initial 510(k) focusing on the most common causes of sepsis: Escherichia coli and Staphylococcus sp (both coagulate negative species and S. aureus), which account for ~60% of blood stream infections. Once the device has obtained 510(k) approval for this limited indication of use, we propose to file abbreviated 510(k) for the detection of additional bacteria (listed in the body of the Work Plan) as additional data is acquired during the clinical trial.

描述（由申请人提供）：仅 34% 的此类严重脓毒症病例的血培养结果呈阳性，抗生素的选择通常基于患者的临床病史。在危及生命的病例中，在获得培养结果之前开始使用广谱抗生素进行治疗，因为在前 48 小时内开始治疗可以显着降低死亡率。 IQuum 开发了一种管内实验室 (Liat(tm)) 分析仪，可用于在患者到达急诊室后 1 小时内检测血流感染。该技术使经过最低限度培训的医疗保健从业人员能够使用全血作为样本输入进行核酸测试。我们建议开发一种逆转录聚合酶链式反应 (RT-PCR) 诊断方法来检测 16S 核糖体 RNA。由于 RT-PCR 检测中每个细胞含有 1,000 至 10,000 个 rRNA 拷贝，因此该装置的预期灵敏度将允许检测约 3 个细胞/10 ml 全血的菌血症滴度。我们建议使用 BUGS'n BEADS(tm) (Genpoint AS) 或凝集素涂层过滤器进行样品制备；一种基于细菌初始吸附至对细菌具有高亲和力的固相基质的方法。或者，我们将探索细菌 rRNA 的核酸特异性捕获。所有这些样品制备替代方案都将使用相同的诊断设备进行测试。 我们进一步建议获得 FDA 对多重检测的批准，并寻求该设备的 CLIA 豁免状态。我们建议提交初始 510(k)，重点关注败血症最常见的原因：大肠杆菌和葡萄球菌（均为凝固阴性菌种和金黄色葡萄球菌），它们约占血流感染的 60%。一旦设备获得 510(k) 批准用于这种有限的使用适应症，我们建议提交缩写 510(k) 用于检测其他细菌（在工作计划正文中列出），因为在临床试验期间会获取其他数据。