Molecular Detection of Blood Stream Infections in Women with Gynecologic Cancer

描述(由申请人提供)：医院感染的估计发病率每年超过200万例。其中，血液感染(BSI)占病例的比例最大，为28%。感染是癌症患者的主要并发症，也是化疗相关死亡的主要原因。许多因素导致了感染风险的增加，包括患者接受的破坏和削弱他们的免疫系统的化疗方案，他们必须经历的漫长的手术程序来切除他们的肿瘤，以及血管内设备的使用，这打破了皮肤的防御屏障。事实上，用于治疗癌症患者的较新的腹膜内疗法在短期内的发病率高于静脉疗法。在发烧的中性粒细胞减少的癌症患者中，BSI实际上占记录的感染的80%-90%；90%的病例与细菌有关，10%与酵母或真菌有关。临床怀疑BSI通常很难证实，因为血培养通常是阴性的。因此，疑似BSI的患者经常接受广谱抗生素的经验性治疗。目前的黄金标准是从血液中培养生物体，这需要时间；细菌需要1-3天才能生长到可以检测到的水平，而酵母和真菌需要更多的时间。一旦一种生物体繁殖到可以检测到的水平，还需要几天的时间来分离和鉴定该生物体并进行抗菌素敏感性测试。利用更快速的方法，如基于分子的方法，在更短的时间内检测和鉴定有机体将对患者产生积极影响；更快的检测可能会降低死亡率。可以更快地修改抗菌疗法，减少广谱抗生素的使用，这反过来又可以减少抗生素相关结肠炎的风险、药物引起的毒性以及选择更具耐药性的微生物的压力。在这项研究中，我们将检验以下假设：在患有BSI风险的妇科恶性肿瘤患者中，实时聚合酶链式反应和快速DNA测序(焦测序)将允许更快速、更准确地检测和识别微生物，就像培养方法一样。将这些技术结合起来直接筛查全血以及从孵化的血液培养瓶中筛选培养液，将是学习如何通过包含基于分子的诊断新的和强大的工具来改进用于诊断高危患者人群中危及生命的血液感染的算法的关键的第一步。

DESCRIPTION (provided by applicant): The estimated incidence of nosocomial infections exceeds 2 million cases per year. Of those, bloodstream infections (BSI) constitute the largest percentage of cases at 28%. Infections are a major complication in cancer patients and are the leading cause of chemotherapy-related mortality. Many factors contribute to this increased risk of infection including the chemotherapeutic regimens received by the patient that damage and weaken their immune system, the lengthy surgical procedures that they must undergo to remove their tumors, and the use of intravascular devices, which breach the skin's defensive barrier. In fact, the newer intraperitoneal therapies used to treat cancer patients have higher morbidities in the short term, than do intravenous therapies. In the febrile neutropenic cancer patient BSI actually accounts for 80-90% of documented infections; bacteria are associated with 90% of cases, and yeast or fungi with 10%. Clinical suspicion of BSI is often difficult to confirm because blood cultures are often negative. As a result, patients with suspected BSI are often treated empirically with broad-spectrum antibiotics. Culturing organisms out of blood, the current gold standard, takes time; bacteria require 1-3 days to grow to detectable levels, while yeast and fungi require even more time. Once an organism multiplies to detectable levels, several more days are needed to isolate and identify the organism and to perform antimicrobial susceptibility testing. Utilizing a more rapid means, such as a molecular-based approach to detect and identify the organism in less time would have a positive impact on the patient; quicker detection could result in reduced mortality. Antimicrobial therapies could be modified sooner, reducing the use of broad-spectrum antibiotics, which in turn could reduce the risk of antibiotic associated colitis, drug-induced toxicity, and the pressure to select more resistant organisms. In this study, we will test the following hypothesis: In women with a gynecologic malignancy at risk for BSI, real-time PCR and rapid DNA sequencing (pyrosequencing) will permit a more rapid, yet as accurate a means of detecting and identifying organisms as that of culture. Combining these techniques to screen whole blood directly as well as screening culture fluid from incubating blood culture bottles will be a critical first step in learning how to improve the algorithms used to diagnose life-threatening bloodstream infections in high-risk patient populations, by encompassing the newer and powerful tools of molecular-based diagnostics.