Molecular Detection of Blood Stream Infections in Women with Gynecologic Cancer

妇科癌症女性血流感染的分子检测

• 批准号: 7738505
• 负责人: JEANNE ANN JORDAN
• 金额: $ 30.89万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2012-11-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7738505
• 关键词: Accounting; Adopted; Algorithms; Antibiotic-Associated Colitis; Antibiotics; Antimicrobial susceptibility; Bacteria; Blood; Cancer Patient; Clinical; Complication; Cost Savings; DNA Sequence; Detection; Development; Devices; Diagnosis; Diagnostic; Dose; Fever; Goals; Gold; Gynecologic; Hour; Immune system; Incidence; Incubated; Infection; Intravenous; Laboratories; Learning; Life; Liquid substance; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Microbial Drug Resistance; Molecular; Morbidity - disease rate; Nosocomial Infections; Operative Surgical Procedures; Organism; Patients; Performance; Pharmaceutical Preparations; Physicians; Regimen; Resistance; Risk; Screening procedure; Sepsis; Skin; Stream; Techniques; Testing; Time; Toxic effect; Whole Blood; Woman; Yeasts; antimicrobial; base; chemotherapy; drug resistant bacteria; fungus; high risk; improved; intraperitoneal therapy; mortality; patient population; pressure; tool; tumor

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.

描述（由申请人提供）：估计每年医院感染发生率超过 200 万例。其中，血流感染 (BSI) 所占病例比例最大，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能力。障碍。事实上，用于治疗癌症患者的新型腹膜内疗法在短期内的发病率比静脉内疗法更高。在发热性中性粒细胞减少性癌症患者中，BSI 实际上占已记录感染的 80-90%； 90% 的病例与细菌有关，10% 的病例与酵母或真菌有关。由于血培养通常呈阴性，因此临床怀疑 BSI 通常很难确认。因此，疑似 BSI 的患者经常接受广谱抗生素的经验治疗。目前的黄金标准是用血液培养生物体，但需要时间。细菌需要 1-3 天才能生长到可检测的水平，而酵母和真菌则需要更长的时间。一旦微生物繁殖到可检测的水平，就需要几天的时间来分离和鉴定该微生物并进行抗菌药物敏感性测试。利用更快速的手段，例如基于分子的方法，在更短的时间内检测和识别生物体将对患者产生积极影响；更快的检测可以降低​​死亡率。可以更快地修改抗菌疗法，减少广谱抗生素的使用，从而降低抗生素相关性结肠炎的风险、药物引起的毒性以及选择更具耐药性微生物的压力。在这项研究中，我们将检验以下假设：对于患有 BSI 风险的妇科恶性肿瘤的女性，实时 PCR 和快速 DNA 测序（焦磷酸测序）将提供一种更快速、更准确的检测和识别生物体的方法，文化的。结合这些技术来直接筛选全血以及筛选培养血培养瓶中的培养液，将是学习如何改进用于诊断高危患者群体中危及生命的血液感染的算法的关键的第一步，方法包括更新且强大的分子诊断工具。