Timing of appropriate empirical antimicrobial administration and outcome of adults with community-onset bacteremia

Background: Early administration of appropriate antimicrobials has been correlated with a better prognosis in patients with bacteremia, but the optimum timing of early antibiotic administration as one of the resuscitation strategies for severe bacterial infections remains unclear. Methods: In a retrospective cohort study, adults with community-onset bacteremia at the emergency department (ED) were analyzed. Effects of different cutoffs of time to appropriate antibiotic (TtAa) administration after arrival at the ED on 28-day mortality were examined, after adjustment for independent predictors of mortality identified by multivariate regression analysis. Results: Among 2349 patients, the mean (interquartile range) TtAa was 2.0 (<1 to 12) hours. All selected cutoffs of TtAa, ranging from 1 to 96 hours, were significantly associated with 28-day mortality (adjusted odds ratio (AOR), 0.54-0.65, all P < 0.001), after adjustment of the following prognostic factors: fatal comorbidities (McCabe classification), critical illness (Pitt bacteremia score (PBS) >= 4) on arrival at the ED, polymicrobial bacteremia, extended-spectrum betalactamase- producer bacteremia, underlying malignancies or liver cirrhosis, and bacteremia caused by pneumonia or urinary tract infections. The adverse impact of TtAa on 28-day mortality was most evident at the cutoff of 48 hours, as the lowest AOR was identified (0.54, P < 0.001). In subgroup analyses, the most evident TtAa cutoff (i.e., the lowest AOR) remained at 48 hours in mildly ill (PBS = 0; AOR 0.47; P = 0.04) and moderately ill (PBS = 1-3; AOR 0.55; P = 0.02) patients, but shifted to 1 hour in critically ill patients (PBS >= 4; AOR 0.56; P < 0.001). Conclusions: The time from triage to administration of appropriate antimicrobials is one of the primary determinants of mortality. The optimum timing of appropriate antimicrobial administration is the first 48 hours after non-critically ill patients arrive at the ED. As bacteremia severity increases, effective antimicrobial therapy should be empirically prescribed within 1 hour after critically ill patients arrive at the ED.