Abstract
BACKGROUND: Real-world evidence regarding the efficacy of isavuconazole (ISA) for pediatric invasive fungal infections (IFIs) remains scarce, particularly in Asia. METHODS: This retrospective multicenter observational study (January 2022-June 2025) was conducted at four tertiary hospitals in central China. Children aged 1-17 years with IFI who received ISA for ≥7 days were included. Therapeutic drug monitoring (TDM) of trough concentrations (C(trough)) was performed using LC-MS/MS targeting 2-4 mg/L. The clinical pharmacists provided weekly antifungal stewardship interventions. RESULTS: Ten children (median age, 6.5 years [range, 2 months-16 years]; 50% male) were enrolled. ISA was used as salvage therapy in 80% of patients due to failure or toxicity of prior antifungal agents. The median treatment duration was 43.5 days (range: 10-318 days). The initial median C(trough) was 1.7 mg/L (range 0.9-5.1); and 60% of the patients were subtherapeutic (<2 mg/L). Pharmacist-led dose escalation (33-100%) achieved target attainment in 83% of the adjusted cases. The favorable response (complete/partial) on day 42 was 80%, and a child died due to bacterial sepsis. A median estimated AUC(0-24)/MIC (183.5) strongly predicts the success of mold infections. No QTc prolongation or severe hepatotoxicity was observed. CONCLUSION: This first Chinese multicenter pediatric series demonstrated the excellent efficacy and tolerability of ISA when combined with routine TDM and clinical pharmacist stewardship. It should be noted that our study has a small sample size, requiring further validation.