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.