Optimizing Vancomycin Area under the Concentration-Time Curve Targets in Enterococcal Bacteremia: Balancing Efficacy and Nephrotoxicity.

Abstract

Purpose: Vancomycin is critical in treating enterococcal bacteremia; however, its optimal pharmacokinetic (PK)/pharmacodynamics (PD) targets remain unclear. This study evaluates the association between vancomycin PK/PD parameters and clinical outcomes in patients with enterococcal bacteremia.

Materials and methods: This retrospective cohort study included 70 patients with enterococcal bacteremia treated with vancomycin at a university-affiliated teaching hospital. The primary and secondary outcomes were unfavorable clinical outcome (30-day mortality or persistent bacteremia) and nephrotoxicity, respectively. Vancomycin area under the concentration-time curve (AUC)/minimal inhibitory concentration (MIC) was calculated using Bayesian methods. Receiver operating curve (ROC) analysis determined AUC/MIC thresholds for predicting unfavorable clinical outcomes and nephrotoxicity. Logistic regression analysis identified risk factors for clinical outcomes.

Results: Unfavorable outcome occurred in 21 patients (30.0%), and 10 (14.3%) experienced nephrotoxicity. The ROC-derived AUC₂₄/MIC cutoff for unfavorable outcome and nephrotoxicity were AUC₂₄/MIC ≥466.0 [AUC=0.740; 95% confidence interval (CI), 0.618-0.862] and ≥643.2 (AUC=0.963; 95% CI, 0.922-1.000), respectively. Clinical success was achieved in 44.9% (22/49) of patients with an AUC₂₄/MIC <400, whereas 47.6% (10/21) experienced unfavorable outcome despite having an AUC₂₄/MIC of 400-600. Nephrotoxicity [adjusted odds ratio (aOR)=15.05; 95% CI, 2.15-105.14; p=0.006] and Charlson Comorbidity Index (CCI) (aOR=1.57; 95% CI, 1.18-2.08; p=0.002) were independent risk factors for unfavorable outcome. High AUC₂₄/MIC and CCI were associated with nephrotoxicity (aOR=1.03; 95% CI, 1.01-1.04; p=0.005, and aOR=1.83; 95% CI, 1.01-3.35; p=0.045).

Conclusion: Nephrotoxicity and multiple comorbidities were stronger risk factors for unfavorable outcomes than vancomycin AUC/MIC. These findings highlight the need for individualized strategies to optimize efficacy while minimizing toxicity. Further large-scale studies are warranted to refine the optimal AUC/MIC threshold.