Molecular Detection of Blood Stream Infections in Women with Gynecologic Cancer

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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.