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Are standard dosing regimens of Amikacin suitable in Critically Ill Patients with Open Abdomen and Negative Pressure Wound Therapy? A population pharmacokinetic study.

Research paper by Cédric C Carrié, Faustine F Delzor, Stéphanie S Roure, Vincent V Dubuisson, Laurent L Petit, Mathieu M Molimard, Dominique D Breilh, Matthieu M Biais

Indexed on: 24 Jan '20Published on: 23 Jan '20Published in: Antimicrobial agents and chemotherapy



Abstract

To assess the appropriateness of recommended regimens for empirical MIC coverage in critically ill patients with open abdomen and negative pressure therapy (OA/NPT). Over a 5-year period, every critically ill patient who received amikacin and who underwent therapeutic drug monitoring (TDM) while treated by OA/NPT was retrospectively included. A population PK modelling was performed considering the effect of ten covariates (age, sex, TBW, ABW, BSA, modified SOFA score, vasopressor use, CL, fluid balance and amount of fluids collected by the NPT over the sampling day) in patients who underwent or not continuous renal replacement therapy (CRRT). Monte Carlo simulations were employed to determine the fractional target attainment (FTA) for the PK/PD targets (C/MIC ratio ≥ 8 and AUCMIC ≥ 75). Seventy critically ill patients treated by OA/NPT (contributing for 179 concentration values) were included. Amikacin PK concentrations were best described by a two-compartment model with linear elimination and proportional residual error, with CL and ABW as significant covariates for Vd and CL for CL. The reported volume of distribution (Vd) in non-CRRT and CRRT patients was 35.8 and 40.2 L respectively. In Monte Carlo simulations, ABW-adjusted doses between 25 and 35 mg/kg were needed to reach an FTA > 85% for various renal functions. Despite an increased Vd and a wide inter-individual variability, desirable PK/PD targets may be achieved using an ABW-pondered loading dose of 25 - 30 mg/kg. When targeting less susceptible pathogens, higher dosing regimens are probably needed in ARC patients. Further studies are needed to assess the effect of OA/NPT in PK parameters of antimicrobial agents. Copyright © 2020 American Society for Microbiology.