Rapid Detection of Catheter Related Bacteraemia

描述(申请人提供)：中心静脉插管是重症监护和癌症患者护理的重要组成部分。美国每年大约使用500万根中心静脉导管，由于人口老龄化，这一数字预计还会上升。然而，使用中心静脉导管的主要风险是它可能导致菌血症。在使用中心静脉导管的患者中，3-7%(每年150,000-350,000例)发生菌血症，其中10-20%(15,000-70,000例)死亡。除了高死亡率外，每个严重菌血症病例还会产生28,000至40,000美元的直接住院费用。 为了减少菌血症的发生率，一旦出现与菌血症一致的临床症状(例如发烧)，通常就拔掉中心静脉导管。由于发热等临床指标不是导管相关菌血症的可靠指标，因此只有一小部分(15%)拔除的导管被证明是感染源或临床症状。不必要的拔除导管带来了额外的风险和成本，这是重新插入导管和抗生素治疗的结果。一种快速、准确的细菌检测方法，如本文所述，将有助于医生做出准确的拔除导管的决定。我们建议使用我们的基于微粒的扩增(MBA)技术和一类新的细菌标记物来开发一种用于这种预期用途的细菌测试。当MBA技术与新型细菌标记物一起使用时，应该可以开发出一种简单、廉价且高度敏感的测试方法。在这项第一阶段的研究中，我们将从以下几个方面验证MBA技术用于检测导管相关菌血症的可行性：(1)设计和制定一种检测方法，(2)优化检测方法，(3)从速度、特异性、灵敏度和定量能力方面对检测性能进行评估。 这项第一阶段研究和随后的第二阶段研究的成功结果将导致该测试的商业化，这将有助于改善导管相关菌血症的前瞻性诊断，从而改善患者的福祉。

DESCRIPTION (provided by applicant): Central venous catheterization is an essential part of intensive care and cancer patient care. Approximately 5 million central venous catheters are used each year in the U.S., and the number is expected to rise due to aging population. However, the major risk of using central venous catheters is that it can cause bacteraemia. Of the patients with central venous catheters, 3-7% (150,000 to 350,000 cases yearly) develop bacteraemia, of which 10-20% (15,000 to 70,000 cases) are fatal. In addition to high mortality rate, each severe bacteraemia case incurs $28,000 to 40,000 direct hospitalization cost. To reduce the incidence of bacteraemia, central venous catheters are often removed once a clinical symptom (e.g., fever) consistent with bacteraemia appears. Because clinical criteria such as fever are not reliable indicators for catheter related bacteraemia only a small fraction (15%) of the removed catheters are proven to be the source of infection or clinical symptoms. The unnecessary removal of catheter introduces additional risk and cost as a result of catheter reinsertion and antibiotic treatment. A rapid and accurate bacterial test such as the one postulated here would be a useful tool for aiding physicians in making accurate decisions on catheter removal. We propose to use our microparticle based amplification (MBA) technology and a novel class of bacterial markers to develop a bacterial test for such intended use. The MBA technology, when employed together with the novel class of bacterial markers, should permit the development of a test that is simple, inexpensive and yet highly sensitive. In this Phase I study, we will verify the feasibility of the MBA technology for use in detecting catheter related bacteraemia by (1) designing and formulating an assay, (2) optimizing the assay protocol, and (3) evaluating the assay performance in terms of its speed, specificity, sensitivity and quantitative capability. A successful outcome of this Phase I study and subsequent Phase II study will lead to commercialization of the test, which will contribute to the improvement of prospective diagnosis of catheter related bacteraemia and consequently the well being of patients.