Pre-Referral Antibiotics and Mortality Among Adults With Sepsis in Southeast Asia: A Secondary Analysis of a Prospective Cohort Study

Abstract

OBJECTIVE: Early antibiotics are considered critical for bacterial sepsis treatment, although the benefit of this early timing may differ by the presence of shock. Little evidence exists from low- or middle-income settings. In patients referred from community hospitals to a tertiary center, we tested whether pre-referral antibiotic administration is associated with 28-day survival in sepsis, and whether this association differs by the presence of shock. DESIGN: Secondary analysis of a prospective cohort study that enrolled patients from 2013 to 2017 with a primary diagnosis of infection made by an attending physician and at least three Surviving Sepsis Campaign criteria for sepsis. SETTING: Tertiary care hospital in northeastern Thailand. PATIENTS: A total of 2593 adults with sepsis defined by primary diagnosis of infection and modified Sequential Organ Failure Assessment score greater than or equal to 2 who were referred from community hospitals. INTERVENTIONS: Antibiotics administered at the referring community hospital. MEASUREMENTS AND MAIN RESULTS: The median age was 59 years (interquartile range 44-72), 2233 (86.1%) were transferred the same day as initial presentation, and 1897 (73.2%) received antibiotics prior to referral. Blood cultures grew bacteria in 313 (12.1%). Twenty-eight-day mortality was 18.9%. In the propensity score-matched cohort ( n = 722 sepsis without shock, n = 244 septic shock), shock modified the association between pre-referral antibiotics and death (interaction p = 0.001). In patients with septic shock, pre-referral antibiotics were associated with lower hazard of death (hazard ratio [HR], 0.38; 95% CI, 0.19-0.75) but in patients without shock there was no association with hazard of death (HR, 1.36; 95% CI, 0.96-1.92). CONCLUSIONS: In rural Thailand, antibiotic administration prior to referral was associated with lower hazard of death in patients with septic shock. Our findings extend to a resource-limited setting evidence supporting the benefit of early antibiotic administration in septic patients with shock.