Please use this identifier to cite or link to this item: http://docs.prosentient.com.au/prosentientjspui/handle/1/10779
Title: Optimising meropenem dosing in critically ill Australian Indigenous patients with severe sepsis.
Authors: Tsai, Danny
Stewart, Penelope
Goud, Rajendra
Gourley, Stephen
Hewagama, Saliya
Krishnaswamy, Sushena
Wallis, Steven C
Lipman, Jeffrey
Roberts, Jason A
Affiliation: Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Department of Intensive Care Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia; Pharmacy Department, Alice Springs Hospital, Alice Springs, Northern Territory, Australia. Electronic address: d.tsai@uq.edu.au..
Department of Intensive Care Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia..
Department of Intensive Care Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia..
Emergency Department, Alice Springs Hospital, Alice Springs, Northern Territory, Australia..
Department of Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia; Department of Infectious Diseases, The Northern Hospital, Epping, Melbourne, Victoria, Australia..
Department of Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia; Monash Infectious Diseases, Monash Health, Clayton, Melbourne, Victoria, Australia..
Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia..
Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Department of Intensive Care Medicine, The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia..
Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Department of Intensive Care Medicine, The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia..
Issue Date: Nov-2016
Citation: International journal of antimicrobial agents 2016-11; 48(5): 542-546
Abstract: Currently there are no pharmacokinetic (PK) data to guide antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis. This study aimed to determine whether the population pharmacokinetics of meropenem were different between critically ill Australian Indigenous and critically ill Caucasian patients. Serial plasma and urine samples as well as clinical and demographic data were collected over two dosing intervals from critically ill Australian Indigenous patients. Plasma meropenem concentrations were assayed by validated chromatography. Concentration-time data were analysed with data from a previous PK study in critically ill Caucasian patients using Pmetrics. The population PK model was subsequently used for Monte Carlo dosing simulations to describe optimal doses for these patients. Six Indigenous and five Caucasian subjects were included. A two-compartment model described the data adequately, with meropenem clearance and volume of distribution of the central compartment described by creatinine clearance (CLCr) and patient weight, respectively. Patient ethnicity was not supported as a covariate in the final model. Significant differences were observed for meropenem clearance between the Indigenous and Caucasian groups [median 11.0 (range 3.0-14.1) L/h vs. 17.4 (4.3-30.3) L/h, respectively; P <0.01]. Standard dosing regimens (1 g intravenous every 8 h as a 30-min infusion) consistently achieved target exposures at the minimum inhibitory concentration breakpoint in the absence of augmented renal clearance. No significant interethnic differences in meropenem pharmacokinetics between the Indigenous and Caucasian groups were detected and CLCr was found to be the strongest determinant of appropriate dosing regimens.
URI: http://docs.prosentient.com.au/prosentientjspui/handle/1/10779
DOI: 10.1016/j.ijantimicag.2016.08.015
Type: Journal Article
Observational Study
Subjects: Critically ill
Pharmacokinetics
Severe sepsis
β-Lactam
Adult
Aged
Anti-Bacterial Agents
Australia
European Continental Ancestry Group
Female
Humans
Male
Microbial Sensitivity Tests
Middle Aged
Monte Carlo Method
Plasma
Population Groups
Prospective Studies
Sepsis
Thienamycins
Time Factors
Urine
Young Adult
Critical Illness
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