De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock

We set out to assess the safety and the impact on in-hospital and 90-day mortality of antibiotic de-escalation in patients admitted to the ICU with severe sepsis or septic shock.We carried out a prospective observational study enrolling patients admitted to the ICU with severe sepsis or septic shock. De-escalation was defined as discontinuation of an antimicrobial agent or change of antibiotic to one with a narrower spectrum once culture results were available. To control for confounding variables, we performed a conventional regression analysis and a propensity score (PS) adjusted-multivariable analysis.A total of 712 patients with severe sepsis or septic shock at ICU admission were treated empirically with broad-spectrum antibiotics. Of these, 628 were evaluated (84 died before cultures were available). De-escalation was applied in 219 patients (34.9%). By multivariate analysis, factors independently associated with in-hospital mortality were septic shock, SOFA score the day of culture results, and inadequate empirical antimicrobial therapy, whereas de-escalation therapy was a protective factor [Odds-Ratio (OR) 0.58; 95% confidence interval (CI) 0.36-0.93). Analysis of the 403 patients with adequate empirical therapy revealed that the factor associated with mortality was SOFA score on the day of culture results, whereas de-escalation therapy was a protective factor (OR 0.54; 95% CI 0.33-0.89). The PS-adjusted logistic regression models confirmed that de-escalation therapy was a protective factor in both analyses. De-escalation therapy was also a protective factor for 90-day mortality.De-escalation therapy for severe sepsis and septic shock is a safe strategy associated with a lower mortality. Efforts to increase the frequency of this strategy are fully justified.