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Development of a Predictive Dosing Nomogram to Achieve PK/PD Targets of Amikacin Initial Dose in Critically Ill Patients: A Non-Parametric Approach

French guidelines recommend reaching an amikacin concentration of ≥8 × MIC 1 h after beginning infusion (C(1h)), with MIC = 8 mg/L for probabilistic therapy. We aimed to elaborate a nomogram guiding clinicians in choosing the right first amikacin dose for ICU patients in septic shock. A total of 138...

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Detalles Bibliográficos
Autores principales: Coste, Anne, Bellouard, Ronan, Deslandes, Guillaume, Jalin, Laurence, Roger, Claire, Ansart, Séverine, Dailly, Eric, Bretonnière, Cédric, Grégoire, Matthieu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854650/
https://www.ncbi.nlm.nih.gov/pubmed/36671324
http://dx.doi.org/10.3390/antibiotics12010123
Descripción
Sumario:French guidelines recommend reaching an amikacin concentration of ≥8 × MIC 1 h after beginning infusion (C(1h)), with MIC = 8 mg/L for probabilistic therapy. We aimed to elaborate a nomogram guiding clinicians in choosing the right first amikacin dose for ICU patients in septic shock. A total of 138 patients with 407 observations were prospectively recruited. A population pharmacokinetic model was built using a non-parametric, non-linear mixed-effects approach. The total body weight (TBW) influenced the central compartment volume, and the glomerular filtration rate (according to the CKD–EPI formula) influenced its clearance. A dosing nomogram was produced using Monte Carlo simulations of the amikacin amount needed to achieve a C(1h) ≥ 8 × MIC. The dosing nomogram recommended amikacin doses from 1700 mg to 4200 mg and from 28 mg/kg to 49 mg/kg depending on the patient’s TBW and renal clearance. However, a C(through) ≤ 2.5 mg/L 24 h and 48 h after an optimal dose of amikacin was obtained with probabilities of 0.20 and 0.81, respectively. Doses ≥ 30 mg/kg are required to achieve a C(1h) ≥ 8 × MIC with MIC = 8 mg/L. Targeting a MIC = 8 mg/L should depend on local ecology.