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 96hours, 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 beta-lactamase-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 48hours, 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 48hours 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 1hour 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 48hours after non-critically ill patients arrive at the ED. As bacteremia severity increases, effective antimicrobial therapy should be empirically prescribed within 1hour after critically ill patients arrive at the ED.