Effect of delayed antibiotic use on mortality outcomes in patients with sepsis or septic shock: A systematic review and meta-analysis

Background: The use of antibiotics is essential in the treatment of sepsis and septic shock, and delaying their administration may impact patient mortality outcomes. However, there is currently a controversial debate surrounding this issue. In this meta-analysis, we aimed to explore the association between delayed antibiotic use and mortality in patients with sepsis and septic shock. Methods: A systematic search was conducted on PubMed, EMBASE, Web of Science, and Cochrane Library to identify relevant studies published from 2013 to 2023. These studies focused on patients with sepsis or septic shock and provided information on various antibiotic administration times and mortality rates. Two independent reviewers screened and extracted the data. The quality of each study was assessed using the Newcastle-Ottawa Scale, and the collected data were analyzed using STATA 15.1 software. Results: A total of 29 studies were included, consisting of 17 prospective cohort studies and 12 retrospective cohort studies. The meta-analysis showed that compared to administration of antibiotics within 1 h, each hour of delay in antibiotic administration increased the in-hospital mortality (IHM) (OR = 1.041, 95 % CI: 1.021-1.062), and ministration of antibiotics after 1 h increased the IHM (OR = 1.205, 95 % CI: 1.123-1.293). There was no significant change in the 28-day mortality (OR = 1.297, 95 % CI: 0.882-1.906), 90-day mortality (OR = 1.172, 95 % CI: 0.846-1.622), and 1-year mortality (OR = 0.986, 95 % CI: 0.422-2.303). Administration of antibiotics within 3 h may reduce the IHM (OR = 1.297, 95 % CI: 1.011-1.664, p = 0.041), while administration of antibiotics within 6 h showed no significant association with the IHM. Conclusion: The administration of antibiotics beyond 1 h after emergency triage or disease identification is strongly associated with an increased IHM in patients with sepsis or septic shock, and each hour of delay in antibiotic administration may be associated with an increase in the IHM. Furthermore, the use of antibiotics identification beyond 3 h after emergency triage / sepsis or septic shock may also increase the IHM.