Tsai, Danny

Stewart, Penny

Goud, Rajendra

Gourley, Stephen

Hewagama, Saliya

Krishnaswamy, Sushena

Wallis, Steven C

Lipman, Jeffrey

Roberts, Jason A

2016-11

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.

International journal of antimicrobial agents 2016-11; 48(5): 542-546

https://pubmed.ncbi.nlm.nih.gov/27771187/?otool=iaurydwlib

https://hdl.handle.net/10137/5312

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

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

Journal Article

Publication