Delay of active antimicrobial therapy and mortality among patients with bacteremia: Impact of severe neutropenia

Increasing bacterial antimicrobial resistance has prompted physicians to choose broad-spectrum antimicrobials in order to reduce the likelihood of inactive empirical therapy. However, for bacteremic patients already receiving supportive care, it is unclear whether delay of active antimicrobial therapy significantly impacts patient outcomes. We performed a retrospective cohort study of patients with monomicrobial bloodstream infections at a large urban hospital in the United States from 2001 to 2006. We assessed the impact of delay of active antimicrobial therapy on mortality by using multivariable logistic regression modeling with and without propensity score methodology. We evaluated 1,523 episodes of monomicrobial bacterial bloodstream infections at our institution. Nine hundred eighty-three bacteremic episodes (64.5%) were treated with an active antimicrobial agent within 24 h of the index blood culture; the remaining 540 episodes (35.5%) were considered to have delay of active antimicrobial therapy. In adjusted analysis, among patients in the nonintensive-care-unit setting with an absolute neutrophil count (ANC) of < 100 cells/mu l, delay was associated with increased mortality (odds ratio [OR], 18.0; 95% confidence interval [CI], 2.84 to 114.5; P < 0.01); among intensive-care-unit patients with an ANC of < 100 cells/mu l, the effect of delay on mortality was nearly significant (OR, 5.56; 95% CI, 0.85 to 36.3; P = 0.07). However, for patients who were nonneutropenic ( ANC, > 500 cells/mu l) or had ANCs of 100 to 500 cells/mu l, delay was not associated with increased mortality. While the delay of active antimicrobial therapy was not significantly associated with higher mortality for most patients in this cohort, patients with severe neutropenia appeared to be vulnerable.