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Optimal Dosing of Meropenem in a Small Cohort of Critically Ill Children Receiving Continuous Renal Replacement Therapy.

Publication ,  Journal Article
Tan, WW; Watt, KM; Boakye-Agyeman, F; Cohen-Wolkowiez, M; Mok, YH; Yung, CF; Chan, YH
Published in: J Clin Pharmacol
June 2021

Severe sepsis is an important cause of mortality and morbidity in critically ill children. Meropenem is a broad-spectrum antibiotic commonly used to treat sepsis. Current meropenem dosage recommendations for children on continuous renal replacement therapy are extrapolated from pharmacokinetic (PK) studies done in adults. Our study aims to determine the optimal dosing in critically ill septic children receiving continuous renal replacement therapy. A prospective single-center PK study was performed in 9 children in the intensive care unit on continuous renal replacement therapy. Meropenem concentrations were measured from blood and effluent fluid samples. A population PK model was developed using nonlinear mixed-effects modeling software (NONMEM, AstraZeneca UK Ltd, Cheshire, UK). Monte Carlo simulations were performed. The PK/pharmacodynamic target aimed for plasma concentrations above minimum inhibitory concentration of 4 mg/L for 100% of dosing interval (100%ƒT>MIC ). A 2-compartment model best characterized meropenem PK. Mean (range) clearance and elimination half-life was 0.091 L/h/kg (0.04-0.157) and 3.9 hours (2.1-7.5), respectively. Dosing of 40 mg/kg/dose every 12 hours over 30 minutes achieved PK/PD target in only 32% while 20 mg/kg every 8 hours over 4 hours or 40 mg/kg every 8 hours over 2 hours achieved 100% ƒT>MIC target for at least 90% of simulated patients.

Duke Scholars

Published In

J Clin Pharmacol

DOI

EISSN

1552-4604

Publication Date

June 2021

Volume

61

Issue

6

Start / End Page

744 / 754

Location

England

Related Subject Headings

  • Sepsis
  • Prospective Studies
  • Pharmacology & Pharmacy
  • Microbial Sensitivity Tests
  • Metabolic Clearance Rate
  • Meropenem
  • Male
  • Intensive Care Units
  • Infant
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Tan, W. W., Watt, K. M., Boakye-Agyeman, F., Cohen-Wolkowiez, M., Mok, Y. H., Yung, C. F., & Chan, Y. H. (2021). Optimal Dosing of Meropenem in a Small Cohort of Critically Ill Children Receiving Continuous Renal Replacement Therapy. J Clin Pharmacol, 61(6), 744–754. https://doi.org/10.1002/jcph.1798
Tan, Wei Wei, Kevin M. Watt, Felix Boakye-Agyeman, Michael Cohen-Wolkowiez, Yee Hui Mok, Chee Fu Yung, and Yoke Hwee Chan. “Optimal Dosing of Meropenem in a Small Cohort of Critically Ill Children Receiving Continuous Renal Replacement Therapy.J Clin Pharmacol 61, no. 6 (June 2021): 744–54. https://doi.org/10.1002/jcph.1798.
Tan WW, Watt KM, Boakye-Agyeman F, Cohen-Wolkowiez M, Mok YH, Yung CF, et al. Optimal Dosing of Meropenem in a Small Cohort of Critically Ill Children Receiving Continuous Renal Replacement Therapy. J Clin Pharmacol. 2021 Jun;61(6):744–54.
Tan, Wei Wei, et al. “Optimal Dosing of Meropenem in a Small Cohort of Critically Ill Children Receiving Continuous Renal Replacement Therapy.J Clin Pharmacol, vol. 61, no. 6, June 2021, pp. 744–54. Pubmed, doi:10.1002/jcph.1798.
Tan WW, Watt KM, Boakye-Agyeman F, Cohen-Wolkowiez M, Mok YH, Yung CF, Chan YH. Optimal Dosing of Meropenem in a Small Cohort of Critically Ill Children Receiving Continuous Renal Replacement Therapy. J Clin Pharmacol. 2021 Jun;61(6):744–754.

Published In

J Clin Pharmacol

DOI

EISSN

1552-4604

Publication Date

June 2021

Volume

61

Issue

6

Start / End Page

744 / 754

Location

England

Related Subject Headings

  • Sepsis
  • Prospective Studies
  • Pharmacology & Pharmacy
  • Microbial Sensitivity Tests
  • Metabolic Clearance Rate
  • Meropenem
  • Male
  • Intensive Care Units
  • Infant
  • Humans