Delayed targeted antibiotics linked to higher mortality in vancomycin-resistant E. faecium bloodstream infections

Patients with vancomycin-resistant Enterococcus faecium bloodstream infections who waited more than three days for targeted antibiotic therapy showed higher mortality, according to a retrospective cohort study conducted at a single medical center in Taiwan. The study, published in BMC Infectious Diseases, also found that inappropriate empiric therapy was independently associated with 30-day all-cause mortality across the full cohort of patients with E. faecium bloodstream infections.

Enterococcus faecium bloodstream infections are associated with high mortality and limited treatment options. A practical complication is diagnostic delay: after Gram-positive cocci are detected in blood cultures, antimicrobial susceptibility results take time to become available, which can complicate the timely initiation of targeted therapy. The study team, led by Ching-Yen Tsai, Chun-Chih Chien and Chen-Hsiang Lee, set out to investigate the association between the timing of appropriate antibiotic therapy and clinical outcomes in these infections.

The retrospective cohort included adult patients with monomicrobial E. faecium bloodstream infections admitted to medical wards, surgical departments, or intensive care units at Kaohsiung Chang Gung Memorial Hospital in Taiwan between January 2011 and June 2023. In total, 336 patients were included: 196 (58.3 percent) had vancomycin-resistant E. faecium (VREF) infections and 140 (41.7 percent) had vancomycin-susceptible E. faecium (VSEF) infections. The primary outcome was 30-day all-cause mortality.

The researchers categorized antibiotic therapy as appropriate empiric therapy (AET) or inappropriate empiric therapy (IET), and then examined whether targeted therapy was initiated within or beyond three days after the bloodstream infection was diagnosed. Kaplan–Meier survival analysis and multivariable Cox proportional hazards regression were used to evaluate the association between antibiotic timing and clinical outcomes.

In the multivariable Cox regression analysis, two factors emerged as independently associated with 30-day all-cause mortality. Higher Sequential Organ Failure Assessment (SOFA) scores carried an adjusted hazard ratio of 1.16 (95 percent confidence interval, 1.01–1.34; p = 0.03), meaning each point increase on the severity score was associated with higher mortality. Appropriate empiric therapy, by contrast, was associated with lower mortality, with an adjusted hazard ratio of 0.30 (95 percent confidence interval, 0.09–0.94; p = 0.04) compared with inappropriate empiric therapy.

The relationship between targeted therapy timing and survival differed according to vancomycin susceptibility. In Kaplan–Meier survival analysis, delayed targeted therapy — initiated more than three days after diagnosis — was associated with higher mortality among patients with VREF bloodstream infections, but not among those with VSEF bloodstream infections. The study’s highlights summarize this pattern: targeted therapy beyond three days was associated with higher mortality in VREF infections, and earlier targeted therapy was associated with better survival in VREF infections.

The authors conclude that higher SOFA scores and inappropriate empiric therapy were associated with higher 30-day all-cause mortality in patients with E. faecium bloodstream infections, and that the association between delayed targeted therapy and mortality differed according to vancomycin susceptibility. They note that timely initiation of effective therapy remains an important clinical consideration in this high-risk population, and that rapid diagnostics may help optimize treatment timing in E. faecium bloodstream infections.

Several caveats are important when interpreting these findings. The study is retrospective and was conducted at a single hospital, so the results describe associations observed in one center’s data rather than causal effects demonstrated in a randomized setting. The article was published as an accepted manuscript shared ahead of the final Version of Record, and is subject to further editorial edits. The findings apply to adult patients with monomicrobial E. faecium bloodstream infections treated at the study hospital during the 2011–2023 period and should not be generalized to other populations, other pathogens, or polymicrobial infections without further research.

Subject of Research: Timing of appropriate antibiotic therapy and 30-day mortality in vancomycin-resistant and vancomycin-susceptible Enterococcus faecium bloodstream infections

Article Title: 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

Article References: Tsai, C.-Y., Chien, C.-C., & Lee, C.-H. (2026). 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. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14716-2

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14716-2

Keywords: Enterococcus faecium, bloodstream infection, vancomycin-resistant, targeted therapy, empiric antibiotic therapy, 30-day mortality, retrospective cohort, SOFA score, Kaplan-Meier analysis, Cox regression, antimicrobial susceptibility, Taiwan