Population pharmacokinetics of intravenous cefotaxime indicates that higher doses are required for critically ill children.
J Antimicrob Chemother
; 77(6): 1725-1732, 2022 05 29.
Article
en En
| MEDLINE
| ID: mdl-35383374
ABSTRACT
BACKGROUND:
Cefotaxime is frequently used in critically ill children, however pharmacokinetic (PK) studies to support adequate dosing in this patient population are limited.OBJECTIVES:
To characterize cefotaxime PK in critically ill children and evaluate exposures achieved by current and alternative dosing regimens.METHODS:
Children (0-18â years) admitted to the paediatric ICU, receiving intravenous cefotaxime (100-150â mg/kg/day, interval 6-8â h) were included (Clinicaltrials.gov NCT03248349). Total plasma cefotaxime concentrations were measured on multiple study days. Population-PK analysis was performed using nonlinear mixed effects modelling (NONMEM™). Dose evaluations were performed using typical patients across the paediatric age range and target attainment was determined for MICs of 0.5, 2 and 4â mg/L.RESULTS:
479 cefotaxime plasma concentrations from 52 children (median age 1.6, range 0.03-17.7â years) were used to describe cefotaxime PK. We describe a two-compartment structural model with interindividual variability, including bodyweight as covariate for volume of distribution and clearance. Model predicted exposure for 150â mg/kg/day (current dose) showed trough concentrations <0.5â mg/L in patients >4â years of age. The maximum cefotaxime doses (200â mg/kg/day, interval 6â h) proved adequate for MICs ≤0.5â mg/L across the whole age range. Similar daily doses with increased frequency (interval 4â h) covered MICs up to 2â mg/L, while a loading dose followed by continuous infusion regimens are needed to adequately treat MICs of 4â mg/L.CONCLUSIONS:
Higher cefotaxime doses are required for adequate exposure for most pathogens in critically ill children. A higher dose frequency or continuous infusion is advisable to improve target attainment for intermediately susceptible pathogens.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Cefotaxima
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Enfermedad Crítica
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
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Child
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Child, preschool
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Humans
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Infant
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Newborn
Idioma:
En
Año:
2022
Tipo del documento:
Article