OBJECTIVE: To evaluate whether resistance to third-generation cephalosporins and/or aztreonam was associated with a higher mortality rate among patients with nosocomial Klebsiella pneumoniae infections. DESIGN: Retrospective cohort study.Setting. Tertiary care university hospital. METHODS: A total of 143 patients with nosocomial infections due to K. pneumoniae were evaluated. Death within 21 days after diagnosis of infection was the outcome. Demographic data, invasive procedures, presence and severity of underlying conditions, infection diagnosis, anatomic site of isolation, and treatment of infection, as well as resistance to third-generation cephalosporins and/or aztreonam, were evaluated for association with the outcome. RESULTS: The mortality associated with nosocomial K. pneumoniae infections was 22% in our study. Drug resistance was found in isolates from 48% of case patients. Multivariate analysis demonstrated that the severity of the patient's underlying condition (odds ratio, 12.50; P<.01) and isolation of the microorganism from the blood or from another usually sterile site (odds ratio, 2.94; P=.03) were associated with death. On the other hand, the presence of resistance to cephalosporins and/or aztreonam did not affect mortality, and the use of inadequate treatment was not significantly associated with increased mortality. When only the severe cases of infection were analyzed, the results were unchanged. CONCLUSIONS: Resistance to cephalosporins and/or aztreonam did not affect mortality, and the use of inadequate treatment was not significantly associated with increased mortality. The reasons for this are not clear. It is possible that the severity of the underlying disease and the patient's condition have a larger role than the K. pneumoniae infection in determining the outcome, and initially inadequate treatment may not have an impact sufficient to cause irreversible damage, allowing treatment to be changed to an effective drug.