Pharmacokinetics and pharmacodynamics of linezolid treatment of bacterial infections in children of different age groups: what do we know today?

Background. Bacterial infections are an important cause of morbidity and mortality in children of different age groups, and Gram-positive flora plays an important role in the development of infections of various localization. Linezolid is one of the main antibiotics used to treat these diseases. It`s pharmacokinetics in children have a number of features that need to be considered in order to optimize therapy to ensure its maximum effectiveness and safety. This is very important for newborn population, and especially for premature infants.

Objective. Search, review, analysis and generalization of the results of pharmacokinetic and pharmacodynamic (PK/PD) studies of linezolid in children of different age groups.

Materials and methods. The information was searched in the scientific electronic library eLIBRARY.ru and the PubMed database for combinations of keywords: «дети или новорождённые» и «линезолид» и «фармакокинетика или фармакокинетический (ая) или ФК/ФД или популяционный (ая) или модельный (ая) или терапевтический лекарственный мониторинг или ТЛМ», as well as «(infant OR newborn OR neonate OR pediatric) AND (linezolid) AND (pharmacokinetic OR PK/PD model (ling) OR population model (ling) OR therapeutic drug monitoring OR TDM» for the period from 01.01.2000 to 31.12.2025. At the initial screening stage, articles describing linezolid pharmacokinetic studies in the pediatric patient population in the treatment of bacterial infections were selected by title and annotation, and at the next stage, full-text identification of selected articles was performed. The analysis did not include studies that lacked the necessary details. Systematic reviews, as well as case reports and studies based on the analysis of adult patient data, were excluded from further consideration.

Results. The studies included into the analysis demonstrated heterogeneous results regarding PK parameter distributions, significant covariates of the PK parameters, optimized dosing regimens to maximize the probability of attaining the desired PK/PD targets. This was most likely due to the high PK variability of linezolid in pediatric populations, as well as the small and heterogeneous patient samples in these studies.

Conclusion. The identified pediatric population PK/PD studies have shown that the pharmacokinetics of linezolid is age-related, and in different age groups is characterized by significant interindividual variability, therefore, standard doses, even taking into account covariates, are not optimal for all patients. Optimization of dosage in the pediatric patient population is possible based on the therapeutic drug monitoring procedure and Bayesian PK/PD modeling.

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