Optimizing Voriconazole Dosing in Extremely Premature Infants With Aspergillus Infections

Background: Primary cutaneous aspergillosis can disseminate in premature infants. Voriconazole, dosed every 12 hours, is the preferred antifungal agent. Prior studies show difficulty achieving therapeutic targets with this regimen. We report the safety and attainment of therapeutic targets with voriconazole dosed q8h with careful therapeutic drug monitoring. Methods: Retrospective review of 4 extremely premature infants with primary cutaneous aspergillosis given voriconazole divided every 8 hours with therapeutic drug monitoring. Demographics, voriconazole administration, treatment duration, need for debridement and patient outcomes were analyzed. Results: All patients survived with complete healing of affected skin. Median voriconazole duration was 69.5 days (min-max 36–84); 69% of voriconazole troughs on intravenous therapy were within the targeted range (1–5 mcg/mL). Troughs on enteral voriconazole were consistently under the targeted range. Few mild, transient adverse effects attributable to therapy were noted. Conclusions: Intravenous voriconazole every 8 hours was safe and consistently met therapeutic targets. Enteral administration consistently failed to achieve therapeutic concentrations.