Kathryn Pavia, Addison Pritchett, Jennifer Goldman
Posaconazole is a triazole antifungal agent used for prophylaxis and treatment of invasive fungal diseases. Posaconazole has high inter-individual variability in dose-exposure relationship and benefits from therapeutic drug monitoring (TDM). Adult studies report particularly high rates of subtherapeutic exposure among intensive care unit (ICU) patients related to changes in physiology during critical illness. The rates of subtherapeutic posaconazole exposure among critically ill children in ICU's are unknown. This single-center retrospective analysis at a large freestanding children's hospital used TDM results from 2010 to 2025 obtained while patients were undergoing care in a pediatric ICU. Therapeutic targets were ≥ 1.0 mg/L for treatment of infection and ≥ 0.7 mg/L for prophylaxis. A general linear mixed model (GLMM) was used to assess factors which differed between instances with therapeutic and subtherapeutic posaconazole concentrations. Sixty-two posaconazole concentrations from 30 ICU patients were analyzed, of which 24 (39%) concentrations were below target based on their therapeutic indication. Both univariate analysis and stepwise GLMM identified an association between liquid formulation and subtherapeutic targets (OR 29.6, CI 2.2-398.2, p = 0.01). However, even among critically ill children with IV posaconazole administration 13/46 (28%) measured concentrations remained subtherapeutic. Rates of subtherapeutic posaconazole exposure among critically ill children are high, though lower than reported from adult ICU cohorts. Liquid formulation use was associated with subtherapeutic concentrations, however appreciable instances of subtherapeutic exposure persist in patients receiving IV administration. Further research is needed to identify characteristics of critically ill patients at risk of subtherapeutic posaconazole exposure and to develop strategies to optimize attainment of appropriate medication exposure.