Optimising meropenem dosing in critically ill Australian Indigenous patients with severe sepsis

Tsai, Danny, Stewart, Penelope, Goud, Rajendra, Gourley, Stephen, Hewagama, Saliya, Krishnaswamy, Sushena, Wallis, Steven C., Lipman, Jeffrey and Roberts, Jason A. (2016) Optimising meropenem dosing in critically ill Australian Indigenous patients with severe sepsis. International Journal of Antimicrobial Agents, 48 5: 542-546. doi:10.1016/j.ijantimicag.2016.08.015


Author Tsai, Danny
Stewart, Penelope
Goud, Rajendra
Gourley, Stephen
Hewagama, Saliya
Krishnaswamy, Sushena
Wallis, Steven C.
Lipman, Jeffrey
Roberts, Jason A.
Title Optimising meropenem dosing in critically ill Australian Indigenous patients with severe sepsis
Journal name International Journal of Antimicrobial Agents   Check publisher's open access policy
ISSN 1872-7913
0924-8579
Publication date 2016-11-01
Sub-type Article (original research)
DOI 10.1016/j.ijantimicag.2016.08.015
Open Access Status Not yet assessed
Volume 48
Issue 5
Start page 542
End page 546
Total pages 5
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Collection year 2017
Language eng
Formatted 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.
Keyword Critically ill
Pharmacokinetics
Severe sepsis
β-Lactam
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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