Activity of isavuconazole and comparator agents against pediatric isolates from invasive fungal infections

Background Invasive fungal infections (IFI) are a rising problem among pediatric patients. Antifungal agents have data supporting treatment in pediatric patients of varying ages and infection types but in vitro susceptibility data for large collections of pediatric isolates is lacking, which limits empiric treatment. We describe in vitro antifungal susceptibility testing (AFST) of 900 contemporary yeast and mold isolates collected from IFI in patients ≤17 years of age as a part of the SENTRY Antifungal Surveillance Program. Methods 900 isolates (743 yeast and 157 molds) were collected from 28 countries between 2017 and 2024. AFST was performed by broth microdilution (BMD) according to Clinical Laboratory and Standards Institute (CLSI) methodology. Results 33.4% of isolates were from patients ≤1 year old, 22.1% from 2–5 years old, 24.4% from 6–12 years old, and 20.0% from 13-17 years old. 63.0% of yeasts were recovered in patients ≤5 years old; 79.6% of molds were in patients ≥6 years old. Most yeast isolates (72.5%) were from bloodstream infections; most mold isolates (61.8%) were from the respiratory tract. By CLSI breakpoints, 88.5% and 87.5% of Aspergillus fumigatus were susceptible to voriconazole and isavuconazole, respectively. Against Mucorales, isavuconazole MIC50 was 4 mg/L and >8 mg/L for voriconazole and posaconazole. All agents had low MICs to most yeasts collected and there were few resistant or non-wildtype yeasts. Conclusions BMD among a diverse collection of isolates obtained from IFI among pediatric patients showed low rates of resistance to echinocandins or azoles. Across species, the lowest MICs were observed for voriconazole and isavuconazole in yeasts. All triazoles were highly active against Aspergillus spp. Against non-Aspergillus molds, isavuconazole, posaconazole, and amphotericin B were the most active agents. This data can guide antifungal treatment of IFI in pediatric patients when susceptibility testing is unavailable.