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Severity of illness scores are helpful in predicting mortality; however, no standardized scoring system has been validated in patients with Staphylococcus aureus bacteremia (SAB). The modified Rapid Emergency Medicine Score (REMS), the CURB-65 (confusion, urea, respiratory rate, blood pressure and age 65) and the Charlson weighted index of comorbidity (CWIC) were compared in predicting outcomes at the onset of SAB.All adult inpatients with SAB from July 15, 2008, to December 31, 2009, were prospectively assessed. The 3 scoring systems were applied: REMS, CURB-65 and CWIC. The end points were attributable and overall mortality.A total of 241 patients with SAB were reviewed during the study period. The all-cause mortality rate was 22.8% and attributable mortality 14.1%. Patients who died had higher mean CURB-65 score and REMS than those who lived, whereas the difference in the CWIC score was not significant. Two logistic regression models based on CURB-65 score or REMS, after controlling for CWIC, revealed that both scores were independent predictors of mortality, with an odds ratio of 3.38 (P < 0.0001) and 1.45 (P < 0.0001) for CURB-65 and REMS, respectively. Receiver operating characteristic analysis revealed that a cutoff point of 3.0 (CURB-65) and 6.0 (REMS) provided the highest sensitivity and specificity. The area under the curves for all-cause mortality were 0.832 and 0.806, and for attributable mortality 0.845 and 0.819, for CURB-65 and REMS, respectively.REMS and CURB-65 scores outperformed CWIC as predictors of mortality in SAB and may be effective in predicting the severity of illness at the onset of bacteremia.