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Master Thesis

Pharmacocinétique de population de l'amikacine chez les patients de réanimation traités par laparostomie avec pansement aspiratif

Abstract : Introduction: the main objective of this study is to characterize the pharmacokinetics (PK) of amikacin and to assess the appropriateness of recommended regimens in patients treated with open abdomen (OA) and negative pressure therapy (NPT). Methods: over a 5 year period, every septic patients who underwent therapeutic drug monitoring (TDM) of amikacin while treated by OA/NPT was retrospectively included for analysis. Multivariable logistic regression was used to determine the risk of amikacin empirical underdosing (Cmax < 60 mg/L) and overdosing (Cmax > 80 mg/L), adjusting for amikacin doses, age, sex, total (TBW) and adjusted body weight (ABW), SOFA score and renal function. A population PK modelling was performed with external validation 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 (Cmax/MIC ratio > 8). Results: over the study period, 70 patients were included (contributing for 179 concentration values). The rate of empirical underdosing was 21%, only depending on the ABW-pondered amikacin dose (p = 0.001). The rate of overdosing was 51%, associated with higher doses (p = 0.001), higher TBW (p = 0.05) and lower CLCR values (p = 0.018). The reported central volume of distribution (Vd) in non-CRRT and CRRT patients was 23.5 and 25.6 L respectively. In Monte Carlo simulations, ABW-adjusted doses between 20 and 35 mg/kg were needed to reach an FTA > 85% for various renal functions. Conclusion: 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.
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Stéphanie Roure. Pharmacocinétique de population de l'amikacine chez les patients de réanimation traités par laparostomie avec pansement aspiratif. Sciences du Vivant [q-bio]. 2020. ⟨dumas-02498643⟩