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To test whether empirical antibiotic treatment that matches the in vitro susceptibility of the pathogen (appropriate treatment) improves survival in patients with bloodstream infections; and to measure the improvement.Observational, prospective cohort study.University hospital in Israel.All patients with bloodstream infections detected during 1988-94.None.In-hospital fatality rate and length of hospitalization.Out of 2158 patients given appropriate empirical antibiotic treatment, 436 (20%) died, compared with 432 of 1255 patients (34%) given inappropriate treatment (P = 0.0001). The median durations of hospital stay for patients who survived were 9 days for patients given appropriate treatment and 11 days for patients given inappropriate treatment. For patients who died, the median durations were 5 and 4 days, respectively (P < 0.05), for both comparisons.In a stratified analysis, fatality was higher in patients given inappropriate treatment than in those given appropriate treatment in all strata but two: patients with infections caused by streptococci other than Streptococcus gr. A and Streptoccocus pneumoniae (odds ratio (OR) of 1.0, 95% confidence interval (95% CI) 0.4-2.5); and hypothermic patients (OR = 0.9, 95% CI = 0.3-2.4). Even in patients with septic shock, inappropriate empirical treatment was associated with higher fatality rate (OR = 1.6, 95% CI = 1.0-2.7). The highest benefit associated with appropriate treatment was observed in paediatric patients (OR = 5.1, 95% CI = 2.4-10.7); intra-abdominal infections (OR = 3.8, 95% CI = 2.0-7.1); infections of the skin and soft tissues (OR = 3.1, 95% CI = 1.8-5.6); and infections caused by Klebsiella pneumoniae (OR = 3.0, 95% CI = 1.7-5.1) and S. pneumoniae (OR = 2.6, 95% C = 1.1-5.9).On a multivariable logistic regression analysis, the contribution of inappropriate empirical treatment to fatality was independent of other risk factors (multivariable adjusted OR = 1.6, 95% CI = 1.3-1.9).Appropriate empirical antibiotic treatment was associated with a significant reduction in fatality in patients with bloodstream infection.