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Master Thesis

Pharmacocinétique et pharmacodynamiques des aminosides dans la mucoviscidose, étude pédiatrique au CHU de Bordeaux

Abstract : Introduction. The vital and functional respiratory prognosis of cystic fibrosis is essentially related to pulmonary colonization by bacteria such as Pseudomonas aeruginosa (PA). Aminoglycoside dosages currently recommended in pediatrics have been inferred from studies in adults or very small cohorts. The objective was to describe the pharmacokinetic parameters in children with cystic fibrosis, and to evaluate the pharmacokinetic / pharmacodynamic correlation (PK / PD) on respiratory function and microbiological colonization of antibiotic cures. Material and methods. In this retrospective single-center observational study, we noted all intravenous antibiotic courses including an aminoglycoside, carried out between 2013 and 2018. Peak and residual plasma assays were performed on the first day of the treatment, pharmacokinetic data were obtained using PK-Just software, and the dosage was individually adapted by Bayesian method. Respiratory function was assessed by FEV1, and bacterial load by cytobacteriological examination of sputum before and after treatment. Results. 493 courses were analyzed in 90 patients between 1 and 19 years old. We observed an increase in clearance, area under the curve and a decrease in half-life compared to a healthy population, with significant differences by age and sex, justifying dosages ranging from 30 at 35 mg / kg / day for amikacin, 15 mg / kg / day for tobramycin and gentamicin. There was a good PK / PD correlation with microbiological colonization (p <0.001), especially when the germ was sensitive. Conclusion. The particular pharmacokinetics in cystic fibrosis requires the use of high doses of aminoglycosides, making monitoring of plasma dosages essential. The emergence of resistance could lead to increased dosages to maintain clinical efficacy.
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Pauline Gallet. Pharmacocinétique et pharmacodynamiques des aminosides dans la mucoviscidose, étude pédiatrique au CHU de Bordeaux. Sciences du Vivant [q-bio]. 2019. ⟨dumas-02493488⟩

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