Delay in the administration of appropriate antimicrobial therapy in Staphylococcus aureus bloodstream infection: a prospective multicenter hospital-based cohort study

Early broad-spectrum antimicrobial treatment reduces mortality in patients with septic shock. In a multicenter, prospective observational study, we explored whether delayed appropriate antimicrobial therapy (AAT) influences outcome in Staphylococcus aureus bloodstream infection (SAB). Two hundred and fifty-six patients with SAB from ten German study centers were enrolled and followed for 3 months. Predisposing factors, clinical features, diagnostic procedures, antimicrobial therapy, and outcome were recorded. The appropriateness of antimicrobial therapy was judged by a trained physician based on in vitro activity, dosage, and duration of therapy. Therapy was considered to be delayed when more than 24 h elapsed between the first positive blood culture and the start of appropriate therapy. The association of delayed therapy with overall mortality and SAB-related events (i.e., attributable mortality or late SAB-related complications) was assessed by crosstabulation and propensity score-based logistic regression. One hundred and sixty-eight patients received AAT during their hospital stay, of whom 42 (25 %) received delayed AAT. The overall mortality and the occurrence of severe sepsis or septic shock were lower in patients with delayed AAT, pointing towards confounding by indication. Adjusted 90-day mortality (adjusted odds ratio [OR] 0.91, 95 % confidence interval [CI] [0.39-2.13], p 0.82) and SAB-related events (adjusted OR 1.46, 95 % CI [0.47-4.51], p 0.52) also failed to show a significant impact of delayed AAT on outcome. In patients with SAB, early AAT may not improve survival. However, confounding by indication is a major challenge when analyzing and interpreting observational studies on the impact of delayed AAT.