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

Danny Tsai, Penelope Stewart, Rajendra Goud, Stephen Gourley, Saliya Hewagama, Sushena Krishnaswamy, Steven C. Wallis, Jeffrey Lipman, Jason A. Roberts

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)542-546
Number of pages5
JournalInternational Journal of Antimicrobial Agents
Volume48
Issue number5
DOIs
Publication statusPublished - 1 Nov 2016
Externally publishedYes

Keywords

  • Critically ill
  • Pharmacokinetics
  • Severe sepsis
  • β-Lactam

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