Time-to-Antibiotics and Clinical Outcomes in Patients With Sepsis and Septic Shock

A Prospective Nationwide Multicenter Cohort Study

Yunjoo Im; Danbee Kang; Ryoung-Eun Ko; Yeon Joo Lee; Sung Yoon Lim; Sunghoon Park; Soo Jin Na; Chi Ryang Chung; Mi Hyeon Park; Dong Kyu Oh; Chae-Man Lim; Gee Young Suh


Crit Care. 2022;26(19) 

In This Article

Abstract and Introduction


Background: Timely administration of antibiotics is one of the most important interventions in reducing mortality in sepsis. However, administering antibiotics within a strict time threshold in all patients suspected with sepsis will require huge amount of effort and resources and may increase the risk of unintentional exposure to broad-spectrum antibiotics in patients without infection with its consequences. Thus, controversy still exists on whether clinicians should target different time-to-antibiotics thresholds for patients with sepsis versus septic shock.

Methods: This study analyzed prospectively collected data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Adjusted odds ratios (ORs) were compared for in-hospital mortality of patients who had received antibiotics within 1 h to that of those who did not. Spline regression models were used to assess the association of time-to-antibiotics as continuous variables and increasing risk of in-hospital mortality. The differences in the association between time-to-antibiotics and in-hospital mortality were assessed according to the presence of septic shock.

Results: Overall, 3035 patients were included in the analysis. Among them, 601 (19.8%) presented with septic shock, and 774 (25.5%) died. The adjusted OR for in-hospital mortality of patients whose time-to-antibiotics was within 1 h was 0.78 (95% confidence interval [CI] 0.61–0.99; p = 0.046). The adjusted OR for in-hospital mortality was 0.66 (95% CI 0.44–0.99; p = 0.049) and statistically significant in patients with septic shock, whereas it was 0.85 (95% CI 0.64–1.15; p = 0.300) in patients with sepsis but without shock. Among patients who received antibiotics within 3 h, those with septic shock showed 35% (p = 0.042) increased risk of mortality for every 1-h delay in antibiotics, but no such trend was observed in patients without shock.

Conclusion: Timely administration of antibiotics improved outcomes in patients with septic shock; however, the association between early antibiotic administration and outcome was not as clear in patients with sepsis without shock.


Take-home Message

Timely administration of antibiotics improved outcomes in patients with septic shock. However, the association between early antibiotic administration and outcome was not as clear in patients with sepsis without shock.

Sepsis is a life-threatening syndrome characterized by physiological, pathological, and biochemical abnormalities that are induced by infection and associated with multiorgan failure and high mortality.[1] Compelling evidence has shown that delay in the initiation of appropriate antibiotic therapy is a risk factor for mortality; therefore, administration of antibiotics is recognized as a key component in the early treatment of sepsis.[2–7] In this regard, antibiotic administration has been included in the hour-1 bundle of the previous Surviving Sepsis Campaign guidelines, and the implementation of the hour-1 bundle was highly recommended to reduce mortality and morbidity.[8,9] Indeed, several multinational studies reported that compliance to the Surviving Sepsis Campaign bundle was associated with mortality in patients with sepsis.[10,11]

Nevertheless, considerable controversy still exists regarding the association between the time of antibiotic administration and clinical outcomes in patients with sepsis/septic shock, and whether the administration of antibiotics within 1 h could improve outcomes in patients with sepsis.[12,13] The Infectious Diseases Society of America recommends that the aggressive administration of antibiotics within 1 h might not be beneficial in sepsis[14] and may result in unintentional exposure to broad-spectrum antibiotics.[15] The American College of Emergency Physicians also noted a lack of evidence to recommend a strict time threshold for antibiotic administration in cases with sepsis.[16] In addition, organizing timely administration of antibiotics requires considerable effort and resources, and it may not be feasible to administer antibiotics within 1 h of presentation in all patients with sepsis.[17]

Thus, this study aimed to evaluate the impact of time-to-antibiotics on in-hospital mortality in patients with sepsis. Furthermore, subgroup analysis was performed to assess whether the effect of time-to-antibiotics was significantly different between the sepsis and septic shock groups.