Early Versus Salvage Combination Antistaphylococcal Therapy for Staphylococcus aureus Bacteremia

Background: Early combination antistaphylococcal therapy may shorten SAB ( Staphylococcus aureus bacteremia) duration, but has not improved survival in unselected populations, with limited tools to identify the patient population to benefit the most. Methods: In a single‑center retrospective cohort study of 80 adults with SAB, we compared early combination therapy (initiated within 72 h of initial blood culture), salvage combination therapy (initiated after 72 h of initial blood culture due to persistent bacteremia), and monotherapy. Subgroup analyses in patients with indwelling cardiovascular or other hardware were performed. Outcomes included bacteremia duration, time to blood culture clearance, on‑treatment bacteremia‑related complications, length of stay, and a composite of in‑hospital mortality or discharge to hospice. Results: Combination therapy initiated after 72 hours of initial blood culture due to persistent SAB was associated with longer bacteremia duration, slower culture clearance, and more on‑treatment complications than monotherapy. In patients with indwelling hardware, early combination therapy was associated with faster bacteremia clearance than salvage therapy, yet without differences in mortality or length of stay. No specific parameter, including SOFA, defining patients likely to benefit from early combination therapy, has been identified. Conclusion: Targeted early combination therapy in addition to source control for device‑associated SAB might improve bacteriologic outcomes. Further prospective, risk‑stratified trials are needed to verify these findings and elaborate clinical tools to identify high-risk patients warranting early combination antistaphylococcal therapy for SAB.