Effect of renal clearance on vancomycin area under the concentration-time curve deviations in critically ill patients

Abstract

Introduction: Augmented renal clearance (ARC) increases vancomycin (VCM) clearance. Therefore, higher VCM doses are recommended in patients with ARC; however, impacts of ARC on the area under the concentration-time curve (AUC) discrepancies between initial dosing design and therapeutic drug monitoring (TDM) period remains unclear.

Methods: We retrospectively collected data from critically ill patients treated with VCM. The primary endpoint was the association between ARC and AUC_24-48h deviations. ARC and AUC deviation were defined as a serum creatinine clearance (CCr) ≥130 mL/min/1.73 m² and an AUC at TDM 30% or more higher than the AUC at the initial dosing design, respectively. The pharmacokinetic profiles of VCM were analyzed with the trough levels or peak/trough levels using the Bayesian estimation software Practical AUC-guided TDM (PAT).

Results: Among 141 patients (median [IQR]; 66 [58-74] years old; 30% women), 35 (25%) had ARC. AUC deviations were significantly more frequent in the ARC group than in the non-ARC group (20/35 [57.1%] and 17/106 [16.0%] patients, respectively, p < 0.001). Age- and sex-adjusted multivariate analyses revealed that the number of VCM doses before TDM ≥5 (odds ratio, 2.56; 95% confidence interval [CI]: 1.01-6.44, p = 0.047) and CCr ≥130 mL/min/1.73 m² were significantly associated with AUC deviations (odds ratio, 7.86; 95%CI: 2.91-21.19, p < 0.001).

Conclusion: Our study clarifies that the AUC of VCM in patients with ARC is higher at the time of TDM than at the time of dosage design.

Keywords: AUC deviations; Augmented renal clearance; Overestimation of renal function; Renal clearance; Therapeutic drug monitoring; Vancomycin.