Infect Chemother.  2020 Dec;52(4):573-582. 10.3947/ic.2020.52.4.573.

Vancomycin Area under the Curve and Pharmacokinetic Parameters during the First 24 Hours of Treatment in Critically Ill Patients using Bayesian Forecasting

• Pongchaidecha M
• Changpradub D
• Bannalung K
• Seejuntra K
• Thongmee S
• Unnual A
• Santimaleeworagun W

• KMID: 2509888
• DOI: http://doi.org/10.3947/ic.2020.52.4.573

Abstract

Background
Currently, the achievement of the target area under the curve (AUC)/ minimum inhibitory concentration ratio during the first 24 - 48 h of treatment is associated with reduced 30-day mortality and greater microbiological eradication in patients with methicillin-resistant Staphylococcus aureus bacteremia. This study aimed to determine the AUC and pharmacokinetic parameters on the first day of vancomycin administration based on the Bayesian theorem to optimize the dosing regimen in critically ill patients.
Materials and Methods
This retrospective study included participants meeting the following criteria: 1) ≥18 years old; 2) receipt of at least one dose of vancomycin; 3) measurement of 2 vancomycin serum concentrations during the first 24 h of treatment; and 4) an intensive care unit admission, mechanical ventilator use, or an Acute Physiology and Chronic Health Evaluation II score >15 points. The AUC on day 1 of treatment and the estimated vancomycin pharmacokinetic parameters were measured using PrecisePK software based on the Bayesian theorem.
Results
We obtained 132 vancomycin concentrations from 66 patients. The vancomycin pharmacokinetic parameters were as follows: AUC_0-24 , 571.09 (± standard deviation [SD] 188.62) mg/L·h; clearance (CL), 2.97 (± SD 1.81) L/h; volume of distribution (Vd), 50.60 (± SD 13.91) L;elimination rate constant, 0.062 (± SD 0.039) h ⁻¹ ; and half-life, 18.19 (± SD 15.96) h. Focusing on the vancomycin loading dose, AUC _0-24 400 - 600 was achieved in 41.7, 46.1, 44.4, and 26.3% of patients with loading doses of <20, 20 – 24.9, 25 – 30, and >30 mg/kg, respectively. Whereas AUC_0-24 ≥521 was achieved in 50, 50, 77.8, and 84.2% of patients with loading doses of <20, 20 – 24.9, 25 – 30, and >30 mg/kg, respectively. The CL of vancomycin was correlated with creatinine CL, whereas the Vd of vancomycin was significantly correlated with age and body weight.
Conclusion
This study revealed that the higher Vd and CL values on the first day of vancomycin therapy were found in critically ill patients. Additionally, a higher vancomycin loading dose (25 – 30 mg/kg) might be required to achieve target of AUC_0-24 during early phase of administration for critically ill patients.

Keyword

AUC; Clearance; Pharmacokinetic; Trough level; Volume of distribution