Clinical and Molecular Epidemiology of Multidrug-Resistant Organisms in a Communi

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DESCRIPTION (provided by applicant): Infections due to multidrug-resistant organisms (MDROs) lead to 100,000 deaths each year in the US, cost the US healthcare system more than $30 billion annually, are increasingly common, are frequently treated inappropriately, and are spreading to community settings. As a result, these infections have been labeled as a "public health crisis" by the CDC. Little is known about the clinical and molecular epidemiology of MDROs in community settings, despite the fact that the majority of care in the US is provided in small community hospitals. Few studies have provided both clinical and molecular data on these pathogens and even fewer have been performed in community hospitals. Thus, the role of the community hospital in the emergence and dissemination of resistance remains unknown. The long-term goal of the PI is to become an independent clinician-scientist performing patient-oriented research (POR) on the clinical and molecular epidemiology of MDRO infections. To achieve this goal, the PI will use a multi-faceted plan to acquire molecular genotyping skills that will enhance his expertise in clinical epidemiology, including close oversight from co-mentors, senior-level guidance from a scientific advisory board of national experts, "hands-on" laboratory training, didactic class work, and completion of POR as outlined herein. This study will provide a better understanding of MDROs in community hospitals using a) the Duke Infection Control Outreach Network (DICON), a unique research resource consisting of 39 community hospitals, and b) previously existing POR, biorepository, and molecular testing infrastructure. The specific aims of the project are to 1) determine the clinical epidemiology of bloodstream infections (BSIs) due to MDROs in a large, prospectively-identified cohort of patients admitted to 10 community hospitals; 2) create a clinical biorepository from prospectively identified patients with infections due to MDROs admitted to a community hospital; and 3) using the newly created biorepository, determine and compare the clinical and molecular epidemiology of patients with infections due to MDR-E. coli, MDR-Klebsiella pneumoniae, or methicillin-resistant Staphylococcus aureus (MRSA) in a community hospital to patients in a tertiary care hospital using specific molecular techniques such as polymerase chain reaction (PCR), pulsed-field gel electrophoresis (PFGE), and repetitive extragenic palindromic (rep)-PCR. The completion of the proposed research will lead to a) the most complete analysis of patients with MDR-BSI in community hospitals to date; b) the creation and validation of a robust, completely unique research infrastructure to perform clinical and molecular POR on a unique, important patient group; c) demonstration of the significant burden of MDR in community hospitals; and d) demonstration of the importance of community hospitals as a source for development of MDR among important pathogens. Infections due to multidrug-resistant organisms (MDROs) lead to adverse patient outcomes, are increasingly common, and are frequently treated inappropriately. Little is known, however, about the clinical and molecular epidemiology of MDROs in community settings, such as community hospitals. Using a unique research resource in the Duke Infection Control Outreach Network, I propose 1) to determine risk factors for inappropriate treatment of and outcomes from bloodstream infections due to MDR-pathogens in community hospitals and 2) after creation of a new, prospective biorepository, to determine and compare the clinical and molecular epidemiology of patients with MDROs in a community hospital to patients in a tertiary care hospital.