Tsai, D; Stewart, Penny; Hewagama, Saliya; Krishnaswamy, S; Wallis, S C; Lipman, J; Roberts, J A

Author(s)

Tsai, D

Stewart, Penny

Hewagama, Saliya

Krishnaswamy, S

Wallis, S C

Lipman, J

Roberts, J A

Publication Date

2018-07

Abstract

Vancomycin is a commonly used antibiotic due to the high burden of methicillin-resistant <i>Staphylococcus aureus</i> infections. This study aimed to describe the pharmacokinetics (PK) of vancomycin in Australian Indigenous patients with severe sepsis, and advise an optimal dosing strategy. A population PK study was conducted in a remote Australian intensive care unit (ICU). Serial plasma samples were collected over one to two dosing intervals and assayed by validated chromatography. Concentration-time data collected were analysed using Pmetrics® software. The final population PK model was then used for Monte Carlo dosing simulations to determine optimal loading and intermittent maintenance doses. Fifteen Indigenous subjects were included for analysis with a median (interquartile range, IQR) age, weight and creatinine clearance (CrCL) of 43 (34-46) years, 73 (66-104) kg and 99 (56-139) ml/minute respectively. A two-compartment model described the data adequately. Vancomycin clearance (CL) and volume of distribution of the central compartment (Vc) were described by CrCL and patient weight respectively. Median (IQR) CL, Vc, distribution rate constants from central to peripheral, and from peripheral to central compartments were 4.6 (3.8-5.6) litres per hour, 25.4 (16.1-31.3) litres, 0.46 (0.28-0.52)/hour and 0.25 (0.12-0.37)/hour respectively. No significant interethnic PK differences were observed in comparison to published data. Therapeutic loading doses were significantly dependent on both weight and CrCL, whereas maintenance doses were dependent on CrCL. In the absence of severe renal impairment, initiation of maintenance dose eight hours post-loading dose achieved higher probability of target attainment at 24 hours. This is the first report of vancomycin PK in this patient group.

Citation

Anaesthesia and intensive care 2018-07; 46(4): 374-380

ISSN

0310-057X

Pubmed ID

https://pubmed.ncbi.nlm.nih.gov/29966110/?otool=iaurydwlib

Link

https://hdl.handle.net/10137/7032

Subject

Indigenous

dosing

pharmacokinetics

severe sepsis

vancomycin

Title

Optimised dosing of vancomycin in critically ill Indigenous Australian patients with severe sepsis.

Type of document

Journal Article

Entity Type

Publication

Author(s)	Tsai, D Stewart, Penny Hewagama, Saliya Krishnaswamy, S Wallis, S C Lipman, J Roberts, J A
Publication Date	2018-07
Abstract	Vancomycin is a commonly used antibiotic due to the high burden of methicillin-resistant <i>Staphylococcus aureus</i> infections. This study aimed to describe the pharmacokinetics (PK) of vancomycin in Australian Indigenous patients with severe sepsis, and advise an optimal dosing strategy. A population PK study was conducted in a remote Australian intensive care unit (ICU). Serial plasma samples were collected over one to two dosing intervals and assayed by validated chromatography. Concentration-time data collected were analysed using Pmetrics® software. The final population PK model was then used for Monte Carlo dosing simulations to determine optimal loading and intermittent maintenance doses. Fifteen Indigenous subjects were included for analysis with a median (interquartile range, IQR) age, weight and creatinine clearance (CrCL) of 43 (34-46) years, 73 (66-104) kg and 99 (56-139) ml/minute respectively. A two-compartment model described the data adequately. Vancomycin clearance (CL) and volume of distribution of the central compartment (Vc) were described by CrCL and patient weight respectively. Median (IQR) CL, Vc, distribution rate constants from central to peripheral, and from peripheral to central compartments were 4.6 (3.8-5.6) litres per hour, 25.4 (16.1-31.3) litres, 0.46 (0.28-0.52)/hour and 0.25 (0.12-0.37)/hour respectively. No significant interethnic PK differences were observed in comparison to published data. Therapeutic loading doses were significantly dependent on both weight and CrCL, whereas maintenance doses were dependent on CrCL. In the absence of severe renal impairment, initiation of maintenance dose eight hours post-loading dose achieved higher probability of target attainment at 24 hours. This is the first report of vancomycin PK in this patient group.
Citation	Anaesthesia and intensive care 2018-07; 46(4): 374-380
ISSN	0310-057X
Pubmed ID	https://pubmed.ncbi.nlm.nih.gov/29966110/?otool=iaurydwlib
Link	https://hdl.handle.net/10137/7032
Subject	Indigenous dosing pharmacokinetics severe sepsis vancomycin
Title	Optimised dosing of vancomycin in critically ill Indigenous Australian patients with severe sepsis.
Type of document	Journal Article
Entity Type	Publication

Optimised dosing of vancomycin in critically ill Indigenous Australian patients with severe sepsis.

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