Evaluation of pharmacokinetic target attainment and hematological toxicity of linezolid in pediatric patients.
Eur J Clin Pharmacol
; 2024 Aug 25.
Article
em En
| MEDLINE
| ID: mdl-39183194
ABSTRACT
BACKGROUND:
Linezolid is commonly used to treat severe and/or resistant Gram-positive infections. Few studies have assessed its pharmacokinetic (PK) target attainment in pediatrics.OBJECTIVE:
To evaluate the percentage of pediatrics achieving the PK targets of linezolid with standard dosing regimens and to assess the incidence and risk factors associated with its hematologic toxicity.METHODS:
This prospective observational study included pediatric patients aged 0-14 who received linezolid for suspected or proven Gram-positive infections. Linezolid trough concentrations and the 24-h area under the curve (AUC24) were estimated, and hematologic toxicity was assessed.RESULTS:
Seventeen pediatric patients (5 neonates and 12 older pediatrics) were included. A wide variability was observed in linezolid's trough and AUC24 (ranging from 0.5 to 14.4 mg/L and from 86 to 700 mg.h/L, respectively). The median AUC24 was significantly higher in neonates than older pediatrics (436 [350-574] vs. 200 [134-272] mg,h/L, P = 0.01). Out of all patients, only 41% achieved adequate drug exposure (AUC24 160-300 mg.h/L and trough 2-7 mg/L), with 24% having subtherapeutic, and 35% having higher-than-optimal exposures. Hematological toxicity was observed in 53% of cases. Identified risk factors include treatment duration over 7 days, baseline platelet counts below 150 × 109/L, sepsis/septic shock, and concomitant use of meropenem.CONCLUSIONS:
Linezolid's standard dosing failed to achieve its PK targets in approximately half of our pediatric cohort. Our findings highlight the complex interplay between the risk factors of linezolid-associated hematological toxicity and underscore the importance of its vigilant use and monitoring, particularly in pediatrics with concomitant multiple risk factors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Eur J Clin Pharmacol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Egito
País de publicação:
Alemanha