Impact of time to antibiotic optimization following inadequate or excessive empiric therapy on clinical outcomes

OBJECTIVE: Inadequate empiric therapy for sepsis has been correlated with heightened mortality; however, bloodstream infections do not uniformly manifest as severe presentations. Empiric administration of broad-spectrum antibiotics may result in adverse events and treatment failure. This study aimed to evaluate the impact of time to antibiotic optimization on outcomes of patients with bloodstream infections who received either inadequate or excessive empiric therapy. METHODS: This single-center retrospective study included patients aged ≥18 years with positive blood culture results and confirmed antimicrobial susceptibility between April 2018 and March 2024. The primary endpoint was a composite outcome of all-cause 30-day mortality, microbiological failure, and antibiotic modification due to insufficient efficacy. The secondary endpoints included adverse event-related discontinuation in the excessive group. RESULTS: = .023). Later optimization (≥100 h) was also linked to higher antibiotic discontinuation due to adverse events. CONCLUSION: Delayed optimization was independently associated with adverse outcomes in cohorts receiving excessive empiric therapy. These findings emphasize the importance of prompt de-escalation of broad-spectrum antibiotics to mitigate treatment failure and treatment discontinuation attributable to adverse events.