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

Abstract

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 Medellín, 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.

Prevention of P2 Receptor-Dependent Thrombocyte Activation by Pore-Forming Bacterial Toxins Improves Outcome in A Murine Model of Urosepsis

“…Sepsis constitutes the host reaction to a circulating infectious agent that potentially leads to life-threatening overstimulation of the immune system and a concomitant hypercoagulable state with a massive micro-thrombus formation and subsequent reduction of the microcirculation. Urinary tract infections are frequently the primary infection-site in patients with sepsis [3], and, thus, E. coli are found in around 30-40% of blood cultures from patients with suspected sepsis [43]. The E. coli that cause severe infection regularly produce a variety of virulence factors, of which HlyA is constantly found in clinical isolates [10].…”

Antimicrobials administration time in patients with suspected sepsis: faster is better for severe patients

“…Secondly, in the study of Ascuntar et al, the overall hospitality mortality rate was low (11.5%), suggesting that most of patients suffered from sepsis and not from septic shock, for which mortality rate usually reaches 40 to 50% [ 3 ]. Although this point was stressed by the authors in their article [ 1 ], we think that this is the major limitation of this work, precluding any application of the results to septic shock patients.…”

“…We read with great interest the recent paper published in the Journal by Ascuntar et al [ 1 ]. reporting the impossibility to demonstrate a significant association between early antibiotic therapy administration and mortality in sepsis patients.…”

“…Last but not least, more than a single intervention, sepsis treatment is based on a bundle of care, as mentioned by Ascuntar et al in the background of their article [ 1 ]. Among many clinical and paraclinical elements, hemodynamic optimization is one of the two most important [ 2 , 4 ].…”

Author’s response to letter “Antimicrobials administration time in patients with suspected sepsis: faster is better for severe patients”

“…Vivien. Their letter to the editor lists several concerns about our previously published article, which evaluated the effect on mortality of early antimicrobial administration in patients with sepsis [1]. Although we believe that these aspects have been mentioned in the article, it is important to return to them.…”