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

Anne-Laure Philippon; Soufiane Lebal; Marta Cancella de Abreu; Camille Gerlier; Oscar Mirò; Tabassome Simon; Yonathan Freund

doi:10.1097/MEJ.0000000000001212

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. 2024 Dec 23. doi: 10.1097/MEJ.0000000000001212. Online ahead of print.

Authors

Anne-Laure Philippon^{1

2}, Soufiane Lebal³, Marta Cancella de Abreu², Camille Gerlier⁴, Oscar Mirò⁵, Tabassome Simon^{1

3}, Yonathan Freund^{1

2}

Affiliations

¹ Sorbonne Université, IMProving Emergency Care (IMPEC) FHU Paris.
² Emergency Department, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP).
³ Department of Clinical Pharmacology and Clinical Research Platform Paris-East (URCEST-CRC-CRB), St Antoine Hospital, APHP.
⁴ Emergency Department, Paris Saint-Joseph Hospital Group, Paris, France.
⁵ Emergency Department, Hospital Clinic, Barcelona, Spain.

PMID: 39704009
DOI: 10.1097/MEJ.0000000000001212

Abstract

Importance: The impact of early antibiotics on mortality in patients with suspected sepsis in the emergency department (ED) remains debated, particularly in patients with less severe presentations or before infection confirmation.

Objective: To evaluate the association between time to antibiotic administration and 28-day in-hospital mortality among patients with suspected sepsis in the ED.

Design, setting, and participants: Post hoc analysis of the 1-bundle emergency department trial, a multicenter, stepped-wedge cluster-randomized controlled trial conducted in 23 EDs in France and Spain. A total of 872 patients with suspected sepsis were included between June 2022 and September 2023. All patients with available data on antibiotic administration were analyzed, and a subgroup of patients with no hypotension was also assessed.

Exposures: Time to antibiotic administration. The effect of time to fluid resuscitation was also assessed.

Main outcomes and measures: The primary outcome was in-hospital mortality at 28 days. Secondary outcomes included all-cause 28-day mortality, ICU length of stay, number of days without vasopressors at day 28, and change in Sequential Organ Failure Assessment score at 72 h.

Results: Among 872 patients (mean age 66 years; 41% female), 859 had available data on antibiotic administration (primary analysis) and 791 (92%) received antibiotics. The median time to antibiotic administration was 61 min (IQR 14-169), with 457 patients (58%) receiving antibiotics within 1 h. In-hospital mortality at 28 days was 14.7% for patients who did not received antibiotic within 1 h versus 9.6% for patients who did [adjusted odds ratio (aOR) 2.00 (1.24-3.23)]. There was an aOR of 1.06 (1.02-1.1) for each hour of delay for antibiotic administration. This effect was confirmed in patients without hypotension [aOR 2.02 (1.08-3.76) for patients who received antibiotics beyond 1 h]. Time to fluid resuscitation was not associated with 28-day in-hospital mortality.

Conclusion and relevance: In patients with suspected sepsis presenting to the ED antibiotic administration beyond 1 h was associated with a two-fold increased 28-day in-hospital mortality. This effect persisted in patients without hypotension.