Similar to the findings of previous studies [4–6], we observed a significant effect of delayed AEA administration on patient survival in the overall cohort. The results of the subgroup analysis revealed that the adverse effects of delayed AEA administration on the prognosis of middle-aged patients were not significant; however, we found that each hour of delay in AEA administration resulted in an average increase of 0.36% and 0.38% in the 30-day crude mortality of old and very old patients, respectively. Moreover, in critically ill patients, each hour of delayed AEA administration contributed to an average increase of 0.3%, 0.4%, and 0.5% in 30-day crude mortality in middle-aged, old, and very old patients, respectively. In sum, regardless of bacteremia severity, the effects of delayed AEA administration on short-term mortality increased with patients’ age.
Studies have reported age-related differences in the distribution of comorbidities, bacteremia sources, and causative microorganisms [8, 10, 19, 20]. Consistent with these findings, a positive age-related trend in bacteremia severity, comorbidity severity, and short-term mortality was observed in the present study. Accordingly, physicians adopted different empirical antimicrobials for patients in different age groups, leading to similar durations of the time to appropriate antibiotic among the different age groups included in this study.
Numerous studies have reported a trend of delay in antimicrobial administration affecting the short-term prognosis of patients with bacteremia in various settings, such as those with community-onset bacteremia [4, 13], severe illness , nosocomial bacteremia , neutropenia , and specific causative microorganisms (i.e., Pseudomonas aeruginosa , S. aureus , and extended-spectrum beta-lactamase-producing Enterobacteriaceae ). Notably, the findings of the present study indicate that regardless of whether a patient was critically ill, the adverse effects of delay in AEA administration on patient survival increased with patients’ age. Accordingly, in older patients with bacteremia episodes, faster AEA administration is recommended. To administer AEAs, epidemiological surveillance of causative microorganisms and susceptibilities or application of the biomolecular technique of rapid pathogen identification is essential for older patients.
Similar to previous studies [4, 27, 28] that have emphasized that severe bacteremia requires earlier AEA administration to achieve favorable outcomes and therapeutic efficacy, we found that each hour of AEA delay resulted in a higher increase in 30-day crude mortality in critically ill patients than in overall patients; that is, middle-aged (0.3% vs. nonsignificant), old (0.4% vs. 0.36%), and very old (0.5% vs. 0.38%) groups. Therefore, regardless of patients’ age, rapid AEA administration is crucial for preventing more severe episodes of bacteremia. Early identification of critically ill patients with bloodstream infections among ED patients through the use of a scoring algorithm, such as the Mortality Emergency Department Sepsis score  or quick Sequential Organ Failure Assessment , is crucial. These tools can assist in accurately assessing bacteremia severity at onset and identifying patients with a high mortality risk.
This study has several limitations. First, consistent with the findings of previous studies regarding the appropriateness of empirical antimicrobial administration [5, 13, 31, 32], no detailed components of the Surviving Sepsis Campaign were evaluated as covariates. However, this study investigated the adverse effects of inadequate source control for complicated bacteremia that are superior to the findings of reports regarding this campaign. Second, because previous studies have reported the neglected difference in therapeutic efficacies between narrow- and broad-spectrum antimicrobials administered as the appropriate empirical agent [33, 34], the differential efficacy between various AEAs was not considered herein owing to the study design being based on previous findings [5, 13, 31, 32]. Third, to investigate the effects of AEA timing on patient prognosis, patients with undetectable antimicrobial administration, incomplete clinical information, or uncertain date of death were excluded. Selection bias may have occurred as a result of the small sample size in this study. Fourth, the retrospective nature of this study made it prone to recall bias during data collection. To reduce this bias, all clinical information was randomly retrieved by two physicians who were blinded to the study hypothesis, and they inspected medical records together to resolve any discrepancies. Fifth, a low E-value was obtained for the prognostic effects of delayed AEA administration on various age groups; thus, unmeasured confounders in our cohort should be trivial. Finally, because study hospitals were located in southern Taiwan, the results of this study should be validated in other communities with variable bacteremia sources, causative microorganisms, or antibiotic-resistant isolates.