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

Manat Pongchaidecha; Dhitiwat Changpradub; Kanjana Bannalung; Kajeewan Seejuntra; Sutthanuch Thongmee; Aminta Unnual; Wichai Santimaleeworagun

doi: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

Infect Chemother. 2020 Dec;52(4):573-582. doi: 10.3947/ic.2020.52.4.573. Epub 2020 Nov 27.

Authors

Manat Pongchaidecha¹, Dhitiwat Changpradub², Kanjana Bannalung¹, Kajeewan Seejuntra³, Sutthanuch Thongmee⁴, Aminta Unnual¹, Wichai Santimaleeworagun^{1

5}

Affiliations

¹ Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand.
² Division of Infectious Diseases, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand.
³ Department of Pharmacy, Ramathibodi Chakri Naruebodindra Hospital, Samutprakarn, Thailand.
⁴ Department of Pharmacy, Chiraprawat Hospital, Nakornsawan, Thailand.
⁵ Antibiotic Optimization and Patient Care Project by Pharmaceutical Initiative for Resistant Bacteria and Infectious Diseases Working Group, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand. swichai1234@gmail.com.

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.

Keywords: AUC; Clearance; Pharmacokinetic; Trough level; Volume of distribution.

Grants and funding

Silpakorn University/Thailand