The optimal target of vancomycin area under the curve in early or later phase on clinical outcomes and nephrotoxicity in patients with enterococcal infective endocarditis: how much is enough?

Enterococcal infective endocarditis (EIE) is associated with substantial morbidity and mortality, while optimal vancomycin pharmacodynamic targets for this condition remain uncertain. To determine the association between vancomycin area under the concentration–time curve to minimum inhibitory concentration ratio (AUC/MIC) and clinical outcomes in patients with EIE. This retrospective cohort study included adult patients with enterococcal infective endocarditis (EIE) who received intravenous vancomycin and had at least one measurable serum concentration. Vancomycin exposure parameters, including the 24-hour area under the concentration–time curve (AUC₀–₂₄, day 1) and steady-state AUC (AUCss), were retrospectively estimated using Bayesian modeling software and were not used to guide dose adjustment during patient care. The primary outcome was 30-day all-cause mortality, and secondary outcomes included microbiological failure and nephrotoxicity defined according to KDIGO criteria. A total of 120 patients with EIE were included. The optimal cut-points for predicting 30-day survival were an AUC₀–₂₄/MIC ≥ 450 and an AUCss/MIC ≥ 420. Patients achieving these thresholds had significantly lower 30-day mortality compared with those below the thresholds. Adequate vancomycin exposure remained independently associated with improved survival. A prespecified AUCss ≥ 650 mg·h/L was associated with increased nephrotoxicity. In multivariate analysis, acute renal failure, septic shock, and low vancomycin AUC/MIC were independent predictors of 30-day mortality, whereas cardiac surgery demonstrated a protective effect. In patients with EIE, achieving AUC₀–₂₄/MIC ≥ 450 or AUCss/MIC ≥ 420 improves survival, whereas AUCss ≥ 650 mg·h/L significantly heightens nephrotoxicity risk. Early AUC-guided dose optimization and renal monitoring are crucial for balancing efficacy and safety in this high-risk population. Not applicable.