Population pharmacokinetics and clinical assessment of linezolid in pediatric bacterial infections.

Abstract

The pharmacokinetic profile of linezolid still needs further definition, and insufficient or excessive exposure may lead to treatment failure or development of adverse events. Our study aimed to establish a population pharmacokinetic (PPK) model for linezolid in children with bacterial infections, develop an optimal dosage, and evaluate its efficacy and safety. A total of 157 plasma samples from 80 patients were utilized in PPK modeling. A one-compartment model with first-order elimination was most suitable for describing the PK characteristics of linezolid. Weight and creatinine clearance were the significant covariates for clearance. The outcomes of Monte Carlo revealed that in children under 12 years, the probability of target attainment (PTA) for standard dosage (10 mg/kg q8h) was over 90.0% when minimum inhibitory concentration (MIC) ≤2 µg/mL, with a mere 1.4% probability of surpassing the safety threshold. Meanwhile, in children aged 12 years and above, the PTA for standard dosage (600 mg q12h) was over 83.0%, and the probability of surpassing the safety threshold was 0.0%. To take the results one step further, a total of 67 patients (using standard dosage) were enrolled in the efficacy and safety analysis. Of the patients, 95.5% were cured or improved clinical treatment outcomes, and 22.4% of the patients developed possible adverse events (AEs), and no patient experienced early discontinuation of linezolid due to AEs. The standard dosage of linezolid is effective and safe in children with bacterial infections (MIC ≤2 µg/mL). For pathogens with MIC >2 µg/mL, it is advisable to switch antibiotics or increase dosage.CLINICAL TRIALSThis study is registered with Chinese Clinical Trial Registry as ChiCTR 2200061207.