Molecular Detection of Blood Stream Infections in Women with Gynecologic Cancer

描述（由申请人提供）：医院感染的估计发生率每年超过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。许多因素导致感染风险增加，包括患者接受的化疗方案损害和削弱了他们的免疫系统，他们必须接受漫长的外科手术来切除肿瘤，以及使用血管内装置，这会破坏皮肤的防御屏障。事实上，用于治疗癌症患者的较新的腹膜内疗法在短期内比静脉内疗法具有更高的发病率。在发热性贫血的癌症患者中，BSI实际上占记录的感染的80-90%;细菌与90%的病例有关，酵母菌或真菌与10%有关。临床怀疑BSI通常难以证实，因为血培养通常为阴性。因此，疑似BSI的患者通常使用广谱抗生素进行经验性治疗。从血液中培养生物体，目前的黄金标准，需要时间;细菌需要1-3天才能生长到可检测的水平，而酵母和真菌需要更多的时间。一旦微生物繁殖到可检测的水平，需要几天时间来分离和鉴定微生物，并进行抗菌药物敏感性测试。利用更快速的手段，如基于分子的方法，在更短的时间内检测和识别微生物，将对患者产生积极的影响;更快的检测可以降低死亡率。抗菌药物治疗可以更快地进行修改，减少广谱抗生素的使用，这反过来又可以降低抗生素相关性结肠炎的风险，药物诱导的毒性以及选择更具耐药性微生物的压力。在这项研究中，我们将测试以下假设：在有BSI风险的妇科恶性肿瘤患者中，实时PCR和快速DNA测序（焦磷酸测序）将允许更快速，但准确的检测和鉴定微生物的方法。结合这些技术直接筛选全血以及从孵育的血培养瓶中筛选培养液将是学习如何改进用于诊断高危患者人群中危及生命的血流感染的算法的关键第一步，包括更新和强大的基于分子的诊断工具。

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.