Timing of appropriate antibiotic therapy and 30-day all-cause mortality in vancomycin-resistant and vancomycin-susceptible Enterococcus faecium bloodstream infections: a retrospective cohort study

Enterococcus faecium (EF) bloodstream infections (BSIs) are associated with high mortality and limited treatment options. Diagnostic delays between the detection of Gram-positive cocci and the availability of antimicrobial susceptibility results often complicate the timely initiation of targeted therapy (TT). We aimed to investigate the association between the timing of appropriate antibiotic therapy and clinical outcomes in patients with EF BSIs. This retrospective cohort study included adult patients with monomicrobial EF BSIs admitted to medical wards, surgical departments, or intensive care units at Kaohsiung Chang Gung Memorial Hospital, Taiwan, between January 2011 and June 2023. The primary outcome was 30-day all-cause mortality. Isolates were stratified according to vancomycin susceptibility as vancomycin-resistant EF (VREF) or vancomycin-susceptible EF (VSEF). Antibiotic therapy was categorized as appropriate empiric therapy (AET) or inappropriate empiric therapy (IET), followed by TT initiated within or beyond 3 days after BSI diagnosis. Kaplan–Meier survival analysis and multivariable Cox proportional hazards regression were performed to evaluate the association between antibiotic timing and clinical outcomes. A total of 336 patients with EF BSIs were included, comprising 196 (58.3%) VREF and 140 (41.7%) VSEF. Multivariable Cox proportional hazards regression analysis identified higher Sequential Organ Failure Assessment (SOFA) scores (adjusted hazard ratio [aHR], 1.16; 95% confidence interval [CI], 1.01–1.34; p = 0.03) and AET (aHR, 0.30; 95% CI, 0.09–0.94; p = 0.04) as independent factors associated with 30-day all-cause mortality. In Kaplan–Meier survival analysis, delayed TT (> 3 days) was associated with higher mortality in patients with VREF BSIs but not in those with VSEF BSIs. Higher SOFA scores and IET were associated with higher 30-day all-cause mortality in patients with EF BSIs. The association between delayed targeted therapy (TT > 3 days) and mortality differed according to vancomycin susceptibility. Timely initiation of effective therapy remains an important clinical consideration in this high-risk population Inappropriate empiric therapy was associated with 30-day all-cause mortality. Targeted therapy > 3 days was associated with higher mortality in VREF BSIs. Earlier targeted therapy was associated with better survival in VREF infections. Rapid diagnostics may help optimize treatment timing in EF BSIs.