Empirical dosage determination of vancomycin for a target area under the concentration-time curve of 400 μg·h/mL in the first 24 h: A prospective multicenter observational study with rich sampling.

Abstract

Aim: Area under the concentration-time curve (AUC)-guided dosing is recommended in vancomycin therapy. This study aims to determine the empirical dosing for achieving an AUC on the first day (AUC_f24h) and the optimal number of samplings for Bayesian estimation.

Methods: A multicentric prospective study was conducted across five hospitals. Critically ill patients were included, with rich sampling conducted on the first day and/or days 3-5 of therapy. Cumulative dose on the first day for the trapezoidal AUC_f24h > 400 μg·h/mL and the predictive performances of AUC and clearance in limited sampling were evaluated. The probability of adherence to AUC_f24h within 400-600 μg·h/mL in the guidelines-compliant or non-compliant doses were also evaluated.

Results: The study included 27 patients and 395 samplings were performed. The mean cumulative dose (standard deviation) on the first day was higher in the group with AUC_f24h > 400 μg·h/mL at 49.3 (4.5) mg/kg compared to the group with AUC_f24h < 400 μg·h/mL at 42.1 (6.8) mg/kg (P = 0.01) for patients with creatinine clearance > 90 mL/min, respectively. The biases and variations of Bayesian posterior AUC by using only a trough concentration were improved by using two-point concentrations at trough and peak. The probability of adherence to AUC_f24h was significantly higher in the guidelines-compliant group (66.7%) than in the non-compliant group (11.1%, P < .01).

Conclusion: This study suggested an empirical dosage of about 50 mg/kg on the first day of vancomycin therapy and the use of two-point sampling in Bayesian estimations to enhance accuracy.

Trial registration: Not applicable because this is a non-intervention study.