Evaluation of target area under the concentration-time curve of vancomycin in an initial dosing design: a retrospective cohort study

Abstract

Objectives: Area under the concentration-time curve (AUC)-guided dosing of vancomycin was introduced in a clinical setting; however, the target range of non-steady-state AUCs, such as Day 1 AUC and Day 2 AUC, remains controversial. Therefore, we sought to determine pharmacokinetic parameter thresholds and identify independent risk factors associated with acute kidney injury (AKI) to establish a safe initial dosing design for vancomycin administration.

Methods: A single-centre, retrospective, cohort study of hospitalized patients treated with vancomycin was conducted to determine the threshold of both non-steady-state AUCs (Day 1 and 2 AUCs) and trough levels at the first blood sampling point (therapeutic drug monitoring, TDM). In addition, independent risk factors associated with AKI were evaluated using univariate and multivariate logistic regression analyses.

Results: The thresholds for predicting AKI were estimated as 456.6 mg·h/L for AUC0-24h, 554.8 mg·h/L for AUC24-48h, 1080.8 mg·h/L for AUC0-48h and 14.0 μg/mL for measured trough levels, respectively. In a multivariate analysis, Day 2 AUC ≥ 554.8 mg·h/L [adjusted odds ratio (OR), 57.16; 95% confidence interval (CI), 11.95-504.05], piperacillin/tazobactam (adjusted OR, 15.84; 95% CI, 2.73-127.70) and diuretics (adjusted OR, 4.72; 95% CI, 1.13-21.01) were identified as risk factors for AKI.

Conclusions: We identified thresholds for both AUCs in the non-steady-state and trough levels at the first TDM. Our results highlight the importance of monitoring not only the AUC but also trough levels during vancomycin treatment to reduce the likelihood of AKI.