Nucleic Acid Diagnostic Device for Quantifying Bacteremi

用于定量细菌的核酸诊断装置

• 批准号: 6999552
• 负责人: BERTRAND LEMIEUX
• 金额: $ 43.4万
• 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/6999552
• 关键词: Escherichia coli infections; Staphylococcus infection; bioassay; biotechnology; blood disorder diagnosis; clinical research; cooperative study; diagnosis design /evaluation; diagnosis quality /standard; early diagnosis; high throughput technology; human subject; microorganism classification; nucleic acid probes; polymerase chain reaction; ribosomal RNA; septicemia

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％的这种严重败血症病例，血液培养结果可用于阳性，而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，先用广谱抗生素开始治疗，因为在最初的48小时内开始治疗可以显着降低死亡率。 Iquum开发了一个实验室（LIAT（TM））分析仪，可用于在急诊室患者出现后1小时内检测血流感染。该技术使受过最低培训的医疗从业人员能够使用全血作为样本输入进行核酸测试。我们建议开发用于检测16S核糖体RNA的逆转录酶聚合酶链反应（RT-PCR）诊断测定法。由于每个细胞包含1,000至10,000份RRNA rRNA的RT-PCR分析，因此该设备的预期灵敏度将允许检测〜3细胞 /10 ml全血的细菌滴度。我们建议使用bugs'n珠（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到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将使用相同的诊断设备进行测试。 我们进一步建议获得多重分析的FDA批准，并寻求该设备的CLIA放弃状态。我们建议将最初的510（k）提交，重点介绍败血症的最常见原因：大肠杆菌和葡萄球菌SP（凝结的阴性物种和金黄色葡萄球菌），占血流感染的约60％。一旦该设备获得了这种有限使用指示的510（k）批准，我们建议在临床试验期间获取其他数据，以归档缩写510（k），以检测其他细菌（在工作计划的正文中列出）。