Mortality and morbidity attributable to inadequate empirical antimicrobial therapy in patients admitted to the ICU with sepsis:: a matched cohort study

Objectives: To determine the attributable mortality and excess length of stay (LOS) associated with the use of inadequate empirical antimicrobial therapy in patients with sepsis at admission to the intensive care unit (ICU). Methods: A retrospective matched cohort study was performed using a prospectively collected database at a 40 bed general ICU at a university public hospital. Patients who received inadequate antimicrobial therapy at admission to the ICU (exposed) were matched with controls (unexposed) on the basis of origin of sepsis, inflammatory response at admission, surgical or medical status, hospital- or community-acquired sepsis, APACHE II score (+/- 2 points) and age (+/- 10 years). Clinical outcome was assessed by in-hospital mortality, and this analysis was also performed in those pairs without nosocomial infection in the ICU. Results: Eighty-seven pairs were successfully matched. Fifty-nine exposed patients died [67.8% mortality (95% CI, 58.0-77.6%)] and 25 unexposed controls died [28.7% mortality (95% CI, 19.2-38.2%)] (P < 0.001). Excess in-hospital mortality was estimated to be 39.1%. The rate of nosocomial infection was significantly higher in patients with inadequate empirical therapy (16.1%) than in those treated empirically with adequate antibiotics (3.4%) (P = 0.013). Excess in-hospital mortality was 31.4% after excluding those 17 pairs that developed a nosocomial infection in the ICU. Inadequate antimicrobial therapy was associated with a significant increment in duration of hospitalization (15 days in surviving pairs). Conclusions: Inadequate antimicrobial therapy at admission to the ICU with sepsis is associated with excess mortality and increases LOS.