Antimicrobials administration time in patients with suspected sepsis: is faster better? An analysis by propensity score

Background Early use of antimicrobials is a critical intervention in the treatment of patients with sepsis. The exact time of initiation is controversial and its early administration may be a difficult task in crowded emergency departments (ED). The aim of this study was to estimate, using a matched propensity score, the effect on hospital mortality of administration of antimicrobials within 1 or 3 hours, in patients admitted to the ED with sepsis. Methods This was a secondary analysis of a multicenter prospective cohort. Patients included in the study were older than 18 years, hospitalized between 2014 and 2016 with suspected sepsis, and admitted to ED of three tertiary care university hospitals in Medellin, Colombia. A propensity score analysis for administration of antimicrobials, both within 1 and 3 h of admission by the ED, was fitted with 28 variables related with clinical attention and physiological changes. As a sensitivity analysis, a logistic regression model was fitted for antimicrobial use adjusted both by propensity score and confounding variables. Results The study cohort was composed of 2454 patients with a median age of 62 years (IQR = 46-74). Among them, 32% (n = 781) received antibiotics within 3 h and 14% (n = 340) within the first hour. The main diagnoses were urinary tract infection (28%, n = 682) and pneumonia (27%, n = 671). Blood cultures were obtained in 87% (n = 2140) and yielded positive in 29% (n = 629), mainly with Escherichia coli (37%, n = 230), Staphylococcus aureus (21%, n = 132), and Klebsiella pneumoniae (10.2%, n = 64). The hospital mortality rate was 11.5% (n = 283). There were no significant differences in mortality, after adjustment, using antimicrobials either in the first hour (OR 1.03; 95% CI = 0.63; 1.70) or 3 h (OR 0.85; 95% CI = 0.61; 1.20). There were no changes with different models for sensitivity analysis. Conclusions Despite the obvious constraints given for sample size and residual confounding, our results suggest that we need a more comprehensive approach to sepsis and its treatment, considering early detection, multiple interventions, and goals beyond the simple time-to-antimicrobials.