DESCRIPTION (adapted from the application) This award will prepare Ebbing Lautenbach M.D., M.P.H., for a career as an independent investigator in Infectious Diseases epidemiology with a particular focus on the proper use of antimicrobial agents and the emergence of antimicrobial resistance. He proposes a comprehensive, interdisciplinary program that will provide him with the skills and experience necessary for independent patient-oriented research. The training component includes advanced education in clinical epidemiology and biostatistics, training in Hospital Epidemiology, and dual mentorship from an internationally recognized pharmacoepidemiologist and a highly experienced Infectious Diseases clinical researcher. The research component of the Award will focus on resistance to the fluoroquinolone (FQ) antibiotics among nosocomial urinary tract infections (UTIs). UTIs are by far the most common of nosocomial infections and are responsible for significant morbidity, mortality, and cost associated with hospitalization. FQ antibiotics have played an increasingly important role in the treatment of nosocomial UTIs particularly as resistance to other first line antibiotics has become widespread. The utility of FQ antibiotics in this setting is, however, seriously threatened by the emergence of resistance to these agents in recent years. Causes of FQ resistance in nosocomial UTIs are unclear and whether risk factors for FQ resistance vary across different infecting organisms has not been studied. This proposal will investigate risk factors for FQ resistance for individual pathogens as well as for gram-positive and gram-negative pathogens as distinct groups. These data will then be used to develop clinical prediction rules for FQ resistance in patients with UTI. Finally, the impact of FQ resistance will be investigated by comparing the outcomes of patients with FQ-resistant and FQ-susceptible infections. This work will provide a basis for the control of the emergence of FQ resistance. Future studies will be planned to evaluate the effect of interventions designed to decrease the emergence of resistance as well as the effect of the prediction rules in selecting more effective empiric antimicrobial therapy for patients with nosocomial UTI.