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Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, Artigas A, Schorr C, Levy MM. Crit Care Med.

Empiric Antibiotic Treatment Reduces Mortality in Severe Sepsis and Septic Shock from the First Hour: Results From a Guideline-Based Performance Improvement Program

Real-world retrospective analysis


  • To perform a retrospective analysis on the Surviving Sepsis Campaign database to evaluate the relationship between timing of antibiotic administration and mortality

This retrospective, multicenter study was conducted to analyze the data collected in the Surviving Sepsis Campaign and evaluate the relationship between the timing of antibiotic administration and mortality.

This study included 28,150 patients from 165 ICUs in Europe, the United States, and South America between January 2005 and February 2010. Eligible subjects for the Surviving Sepsis Campaign were those admitted to an ICU with a suspected site of infection, two or more systemic inflammatory response syndrome criteria, and one or more organ dysfunction criteria.
Patients with previous antibiotic administration, missing antibiotic administration timing data, or no antibiotic administration were excluded from the analysis, resulting in 17,990 remaining patients. The study used a generalized estimation equation (GEE) population averaged logistic regression to analyze the relationship between hospital mortality and time to first antibiotic administration. The model was adjusted for three covariates that the risk factor model identified as confounders or effect modifiers: sepsis severity score (SSS), ICU admission source (ED, ward, vs ICU), and geographic region (Europe, United States, South America).


The analysis found that there was a linear increase in the risk of mortality for each hour delay in antibiotic administration between the first and sixth hour. The probability of mortality increased from 24.6% to 33.1% from hour 0 to 6 (for the following subject characteristics: from the US, admission source is ED, median SSS of 52). The study found there were similar results for patients with either severe sepsis or septic shock, and there were consistent results across levels of illness severity (number of organ failure) and areas of the hospital (ED, ward, or ICU).


The authors acknowledge that as with any retrospective study, there is potential for residual confounding. The study does not assess the appropriateness of antibiotic therapy in the patient population, nor the reasons for the delay in antibiotic administration, which could potentially confound the results. The study supports the importance of prompt antibiotic administration for the survival of severe sepsis and septic shock, and the authors emphasize that sepsis should be recognized as an urgent situation that requires immediate response.

The figure below displays the relationship between antibiotic administration delay and mortality from Figure 2 of the article.


Figure 2. Predicted hospital mortality and the associated 95% CIs for time to first antibiotic administration. The results are adjusted by the sepsis severity score (SSS), ICU admission source (emergency department [ED], ward, vs ICU), and geographic region (Europe, United States, and South America). Probability of hospital mortality is based on the subject having the following specific characteristics: the patient is from the United States, admission source is the ED, and the SSS is 52 (median of all observations).


  • Delay in first antibiotic administration for patients with severe sepsis and septic shock is associated with increased in-hospital mortality
  • There is a linear increase in the risk of mortality for each hour delay in antibiotic administration from the first through sixth hour
  • The results of the study were similar in patients with severe sepsis and septic shock, regardless of the number of organ failure or hospital setting where sepsis was identified
  • Early identification and treatment of septic patients in the hospital setting is very important for reducing mortality 
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