Candidates for area under the concentration–time curve (AUC)-guided dosing and risk reduction based on analyses of risk factors associated with nephrotoxicity in vancomycin-treated patients

Abstract

ABSTRACT: Objectives: : Compared with vancomycin trough concentration (Cmin)-guided dosing, area under the concentration–time curve (AUC)-guided dosing is associated with decreased acute kidney injury (AKI). However, whether Cmin-guided or AUC-guided dosing should be used in patients other than those with serious MRSA infections remains uncertain. The purposes of this multicentre study were to identify risk factors for early- and late-phase vancomycin-induced AKI and to identify candidates for AUC-guided dosing, rather than Cmin-guided dosing, who require a more accurate dose titration to reduce the AKI risk. Methods: : A multivariate logistic regression analysis was applied to identify risk factors for AKI. Additionally, the cut‑off day for AKI onset, cut-off Cmin for AKI, safe Cmin for reduced AKI risk and probability of AKI were calculated. Results: : In total, 8.4% (159/1882) of patients developed AKI. AKI occurred within the first 7 days of therapy (early phase) in the vast majority of patients. Significant risk factors for AKI during the early phase were identified as Cmin > 20 mg/L, ICU stay, concurrent diuretic or piperacillin/tazobactam use, and pre-existing renal dysfunction. A temporarily elevated Cmin (>15–20 mg/L) was not associated with a greater risk of AKI. In patients with risk factors, the cut-off Cmin for AKI and the estimated safe Cmin for reduced AKI risk were 18.8–21.0 mg/L and <11.7–13.5 mg/L, respectively. Conclusion: : Patients with known AKI risk factors require a low target Cmin. The presence of several risk factors for AKI may indicate a need for more accurate dose titration using AUC-guided dosing.

Keywords

• Vancomycin
• Nephrotoxicity
• Acute kidney injury
• Area under the concentration–time curve
• AUC
• Therapeutic drug monitoring