Patients with suspected sepsis in the Emergency Department (ED) have twice the rate of survival at 28 days when antibiotics are started within 1 hour, even when symptoms are not severe and the diagnose is uncertain, according to post-hoc analysis of a trialthat evaluated a sepsis treatment “bundle.”1
Although guidelines2 have emphasized the importance of initiating broad-spectrum antibiotics in sepsis treatment bundles within 1 hour, the timing has been less clear for patients with lower severity of illness, explain Anne-Laure Philippon, MD, PhD, Sorbonne Université, IMProving Emergency Care (IMPEC) FHU and Emergency Department, CHU Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Paris France, and colleagues.
The investigators also point out more recent guidance3 that relaxes time to initiate antibiotics to within 3 hours for patients with suspected sepsis but without severe manifestations.They characterize that guidance as controversial, however, and suggest that the delay increases mortality risk of those with sepsis.
“Early recognition and timely management are crucial for improving outcomes in patients presenting with sepsis, with antimicrobial therapy being a cornerstone of treatment,” Philippon and colleagues declare.
To discern the value of initiating antibiotics within 1 hour for patients with suspected sepsis but less severe presenting symptoms, the investigators conducted post-hoc analysis of the 1-BED trial,4 which had compared outcomes from usual care to that with 1-hr initiation of a sepsis treatment bundle of microbiological cultures, lactate measurement, fluid resuscitation when indicated, and broad-spectrum antibiotics.
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Patients with suspected sepsis who received antibiotics within 1 hour had nearly double the survival rate at 28 days compared to those treated later, even if their symptoms were mild or diagnosis uncertain.
For every hour delay in starting antibiotics, the risk of death increased (adjusted odds ratio: 1.06). The association held true even after controlling for various factors and patient subgroups, reinforcing the urgency of treatment regardless of severity.
While newer guidelines allow up to 3 hours to administer antibiotics in less severe cases, the authors found this delay to be potentially harmful.
Their analysis isolated the association of antibiotic timing with 28-day in-hospital mortality. Secondary measures included all-cause mortality and duration of stay in ICU by day 28.The cohort comprised 872 adult patients with suspected infection and at least one criterion to suspect sepsis(serum lactate >2mmol/L, score on qSOFA [Sequential Organ Failure Assessment] of ≥2, or hypotension).859 patients had data on time of antibiotic initiation, with 791 receiving antibiotics in the ED, and 654 with confirmed infection.
Philippon and colleagues found a 9.6% rate of 28-day in-hospital mortality among patients receiving antibiotic within 1 hour, compared to 14.7% of those started on antibiotics after 1 hour (aOR 2.00; 95%CI 1.24-3.23).Further, there was an aOR of 1.06 (1.02-1.1) for each hour antibiotic initiation was delayed.That result was consistent through 3 sensitivity analyses: with 13 patients with incomplete data, with only those receiving antibiotics in the ED, and with only the patients with confirmed infection.
There was also an association between antibiotics started after 1 hour and increased all-cause day 28 mortality (aOR 2.19, 1.36-3.52).There was no association, however, between the timing of antibiotics and duration of ICU stay at day 28, or in change in SOFA score at 72 hours.
The investigators posit that early antibiotic administration is the main driver of the potential benefit of the sepsis treatment bundle.Although they had earlier reported no statistically significant difference in outcomes between the 1-hour treatment bundle and usual care in the 1-BED trial, they attribute that to most of patients in the control group having also received antibiotics within 1 hour.
“The present study suggests that in all patients, a 1 h timeframe for antibiotic administration should be recommended, because it reportedly improves outcomes, even in a heterogeneous population that includes patients without confirmed sepsis or infection,” Philippon and colleagues conclude.
References
1.Philippon A-L, Lebal S, de Abreu, MC, et al. Association between time to antibiotic and mortality in patients with suspected sepsis in the Emergency Department: Post-hoc analysis of the 1-BED randomized clinical trial. Eur J Emerg Med. 2025 32:109-115.
2.Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign Bundle. 2018 update. Intensive Care Med. 2018; 44:925-928.
3.Evans L, Rhodes A, Alhazzni W, et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021.Intensive Care Med. 2021; 47:1181-1247.
4.Freund Y, Lebal S, Freund Y, et al.. Effect of the 1-h bundle on mortality in patients with suspected sepsis in the emergency department: a stepped wedge cluster randomized clinical trial. Intensive Care Med. 2024; 50:1086-1095.
