Effectiveness, Safety, and Pharmacokinetics of Linezolid in Pediatric Bacterial Central Nervous System Infections.

BACKGROUND:Linezolid shows therapeutic potential for pediatric gram-positive bacterial central nervous system infections (CNSIs). However, its efficacy, safety profile, and cerebrospinal fluid (CSF) pharmacokinetics require detailed evaluation. METHODS:This prospective 2-center observational study enrolled children with confirmed or suspected gram-positive CNSIs. Clinical outcomes and adverse events were compared between linezolid-treated patients and a matched vancomycin cohort. Population pharmacokinetic (PopPK) modeling with nonlinear mixed-effects analysis quantified linezolid exposure in plasma and CSF. RESULTS:Among 45 matched pediatric CNSIs patients per group, linezolid demonstrated a 91.1% clinical response rate and 68.9% cure rate (vancomycin cure rate, 68.9%). However, noninferiority to vancomycin was not established for the primary end point, possibly influenced by intergroup baseline variability and extended treatment duration. Adverse events occurred more frequently with linezolid, including gastrointestinal (48.9% vs 24.4%, P = .02) and hematologic effects (73.3% vs 53.3%, P = .05). Plasma trough concentrations >7 µg/mL were correlated with elevated risk of leukopenia and neutropenia (odds ratio [OR], 9.38; 95% confidence interval [CI], 1.21-72.6 and OR, 40.2; 95% CI, 2.15-748.50). However, no treatment discontinuations occurred due to adverse events. The PopPK model analyzed 135 linezolid concentrations (90 plasma/45 CSF), identifying body weight as the primary covariate influencing distribution. Plasma and CSF trough concentrations showed a strong correlation (r = 0.87; 95% CI, .75-.98). CONCLUSIONS:Linezolid demonstrated favorable clinical efficacy and tolerability in pediatric CNSIs, with CSF concentrations that correlated with plasma levels and exhibited predictable pharmacokinetics.