Association of Delayed Antimicrobial Therapy with One-Year Mortality in Pediatric Sepsis

Objective: Delayed antimicrobial therapy in sepsis is associated with increased hospital mortality, but the impact of antimicrobial timing on long-Term outcomes is unknown. We tested the hypothesis that hourly delays to antimicrobial therapy are associated with 1-year mortality in pediatric severe sepsis. Design: Retrospective observational study. Setting: Quaternary academic pediatric intensive care unit (PICU) from February 1, 2012 to June 30, 2013. Patients: One hundred sixty patients aged ≤21 years treated for severe sepsis. Interventions: None. Measurements and Main Results: We tested the association of hourly delays from sepsis recognition to antimicrobial administration with 1-year mortality using multivariable Cox and logistic regression. Overall 1-year mortality was 24% (39 patients), of whom 46% died after index PICU discharge. Median time from sepsis recognition to antimicrobial therapy was 137min (IQR 65-287). After adjusting for severity of illness and comorbid conditions, hourly delays up to 3h were not associated with 1-year mortality. However, increased 1-year mortality was evident in patients who received antimicrobials ≤1 h (aOR 3.8, 95% CI 1.2, 11.7) or >3h (aOR 3.5, 95% CI 1.3, 9.8) compared with patients who received antimicrobials within 1 to 3h from sepsis recognition. For the subset of patients who survived index PICU admission, antimicrobial therapy ≤1 h was also associated with increased 1-year mortality (aOR 5.5, 95% CI 1.1, 27.4), while antimicrobial therapy >3h was not associated with 1-year mortality (aOR 2.2, 95% CI 0.5, 11.0). Conclusions: Hourly delays to antimicrobial therapy, up to 3 h, were not associated with 1-year mortality in pediatric severe sepsis in this study. The finding that antimicrobial therapy ≤1 h from sepsis recognition was associated with increased 1-year mortality should be regarded as hypothesis-generating for future studies.