Fluconazole Therapeutic Drug Monitoring in Critically Ill Pediatric Patients

Introduction: Fluconazole, a commonly used triazole antifungal agent, exhibits high inter-patient pharmacokinetic (PK) variability, especially in the setting of critical illness and with the use of extracorporeal support modalities. Data are lacking to guide dosing and ensure therapeutic targets are attained while toxicities are minimized in critically ill children. Therapeutic drug monitoring (TDM) has been proposed to optimize therapy, with an AUC24h/MIC of >100, corresponding to a trough of 10-15 mg/L for an MIC of 4 mg/L, suggested for treatment of candidal infections. The aim of this study was to evaluate fluconazole dosing and PK in critically ill pediatric patients.


Methods: This retrospective, single-center, cohort study reviewed electronic medical records of patients ≤17 years of age who received fluconazole with a corresponding fluconazole level in the cardiac (CICU), neonatal (NICU), and pediatric intensive care units (PICU) between July 2023 and July 2025. Data collected included fluconazole dose and frequency, extracorporeal modality used, culture data, and fluconazole trough values.


Results: A total of 9 patients (median age 3.7 years; IQR 2.7-6.4) received fluconazole in the CICU, NICU, and PICU for a Candidal infection, with a total of 12 trough values obtained. Median ICU length of stay was 70 days (IQR 45-148). All patients were supported with an extracorporeal device; 2 with a single ventricle assist device (SVAD), 4 with extracorporeal membrane oxygenation, and 8 with continuous renal replacement therapy (median clearance 2180 mL/1.73m2/hr). Patients were receiving a median fluconazole dose of 12 mg/kg every 24 hours at time of first level, with a median trough of 3.28 mg/L (IQR 1.6-8.2).

Goal trough was attained for only 1 of the 12 levels obtained; fluconazole 12 mg/kg every 24 hours given to a patient with an SVAD resulted in a level of 20.6 mg/L. Three patients received fluconazole 12 mg/kg every 12 hours, with a median trough of 8.2 mg/L, representing subtherapeutic levels. Three patients died while receiving treatment for Candida infection.


Conclusions: Subtherapeutic fluconazole levels are common in pediatric patients, especially for those on extracorporeal modalities. Further studies are needed to determine appropriate fluconazole dosing and the role of TDM in this population.