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

• Published in: Journal of global antimicrobial resistance. Vol. 27; pp. 12 - 19
• Main Authors: Hashimoto, Naoto, Kimura, Toshimi, Hamada, Yukihiro, Niwa, Takashi, Hanai, Yuki, Chuma, Masayuki, Fujii, Satoshi, Matsumoto, Kazuaki, Shigemi, Akari, Kawamura, Hideki, Takahashi, Yoshiko, Takesue, Yoshio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.12.2021; Elsevier
• Subjects: Acute kidney injury; Acute Kidney Injury - prevention & control; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Area Under Curve; Area under the concentration–time curve; AUC; Humans; Microbial Sensitivity Tests; Nephrotoxicity; Risk Factors; Risk Reduction Behavior; Therapeutic drug monitoring; Vancomycin; Vancomycin - administration & dosage; Vancomycin - adverse effects; Therapeutic drug monitoring; Vancomycin; Nephrotoxicity; Acute kidney injury; Area under the concentration–time curve; AUC
• ISSN: 2213-7165; 2213-7173
• DOI: 10.1016/j.jgar.2021.07.018

•The cut-off day for acute kidney injury (AKI) onset was 7.3 days.•The cut-off Cmin associated with AKI was 19.3 mg/L.•Temporarily elevated high Cmin (>15–20 mg/L) due to a loading dose was not associated with a greater risk of AKI.•In patients with risk factors, the cut-off Cmin for AKI was 18.8–21.0 mg/L (14.4–15.8%).•In patients with risk factors, the estimated safe Cmin was <11.7–13.5 mg/L (9.8%). : 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. : 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. : 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. : 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. [Display omitted] [Display omitted]