Evaluation of pharmacokinetic target attainment and hematological toxicity of linezolid in pediatric patients.

Publisher: Springer Country of Publication: Germany NLM ID: 1256165 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1041 (Electronic) Linking ISSN: 00316970 NLM ISO Abbreviation: Eur J Clin Pharmacol Subsets: MEDLINE

Original Publication: Berlin, New York, Springer.

Linezolid*/pharmacokinetics ; Linezolid*/adverse effects ; Linezolid*/administration & dosage ; Linezolid*/blood ; Anti-Bacterial Agents*/pharmacokinetics ; Anti-Bacterial Agents*/adverse effects ; Anti-Bacterial Agents*/administration & dosage; Humans ; Infant ; Child, Preschool ; Child ; Male ; Female ; Adolescent ; Infant, Newborn ; Prospective Studies ; Area Under Curve ; Gram-Positive Bacterial Infections/drug therapy ; Risk Factors

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 (AUC 24 ) 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 AUC 24 (ranging from 0.5 to 14.4 mg/L and from 86 to 700 mg.h/L, respectively). The median AUC 24 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 (AUC 24 160-300 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 × 10 ⁹ /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.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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Keywords: Drug exposure; Hematologic toxicity; Linezolid; Pediatrics; Pharmacokinetics

ISQ9I6J12J (Linezolid)
0 (Anti-Bacterial Agents)

Date Created: 20240825 Date Completed: 20241007 Latest Revision: 20241007

20241007

10.1007/s00228-024-03740-3

39183194