Evaluation of Pharmacokinetic Pharmacodynamic Target Attainment and Hematological Toxicity of Linezolid in Pediatric Patients

Abstract

Background Linezolid is commonly used to treat severe and/or resistant Gram-positive infections. Few studies have assessed its pharmacokinetics/pharmacodynamics (PK/PD) in pediatrics. Objective to evaluate the percentage of pediatric patients achieving the PK/PD target of linezolid using 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 years who received linezolid for suspected or proven Gram-positive infections. Linezolid trough concentrations were measured, and hematologic toxicity was assessed. Results In total, 17 pediatric patients (5 neonates and 12 older pediatrics) were included in the analysis. The median trough concentration in neonates was significantly higher than that of the older pediatrics (7.1 [6.2–11.0] vs. 3.9 [1.95–6.5] mg/L, respectively, P = 0.04). Out of all patients, 53% achieved the therapeutic trough level of 2–7 mg/L, 18% had subtherapeutic levels, and 23% had higher-than-optimal troughs. Linezolid-associated hematological toxicity was documented in 53% of cases. Identified significant risk factors include treatment duration of more than 7 days, baseline platelet counts of less than 150 x 10⁹/L, sepsis/septic shock, and concomitant use of meropenem. Conclusions Linezolid's standard dosing failed to achieve its PK/PD target in approximately half of our pediatric cohort. Our findings underscore the complex interplay between the risk factors of linezolid-associated hematological toxicity and highlight the importance of its vigilant use and monitoring if it is to be initiated in pediatrics with concomitant multiple risk factors.