My research interests focus on the question, "What makes some patients with bacteremia do poorly while others do well?" In order to approach this question, I have generated and continue to generate large prospective cohorts of patients with bacteremia due to gram positive (S. aureus) and gram negative (enterobacteriacea) organisms. In addition to clinical data, the corresponding bloodstream isolate, and patient DNA and serum are being catalogued from patients with bacteremia due to both gram positive and negative pathogens. Because of the increasing frequency and antibiotic resistance of bacterial infections, these pathogens will remain an important topic of patient-oriented research for many years to come. My immediate objective is to identify important determinants of poor clinical outcome in patients with S. aureus bacteremia, utilizing a consecutive cohort of ~1000 patients and corresponding bloodstream isolates collected over the past seven years. In addition, identifying important determinants of poor clinical outcome also requires the use of our bacterial isolates to evaluate the role of virulence factors in S. aureus infection. Identification of these determinants could eventually result in a facile and cost-efficient way to help identify patients at risk for severe metastatic infection, thereby affecting clinical management. One important future direction in translational bacterial outcome studies will be the host. We are uniquely poised to begin inquiries into this field, as well. Over the last two years, we have been collecting DNA and serum samples from patients with bacteremia who provide written informed consent. Borrowing from the model created for our bacterial isolates of collaboration with the laboratory of an established basic science investigator, we plan to combine our efforts with a human geneticist coinvestigator. In this way, we plan to begin to address the role of host "susceptibility factors" in determining outcome in patients with bloodstream infections. The unique resource of large collections of well-characterized clinical cases of bacteremia with available specimens from the corresponding pathogen (e.g., bacterial isolate) and host (e.g., DNA and serum) will offer rich research opportunities for trainees for years to come.