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?

BACKGROUND: Enterococcal infective endocarditis (EIE) is associated with substantial morbidity and mortality, while optimal vancomycin pharmacodynamic targets for this condition remain uncertain. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: Not applicable.