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Published on: April 19, 2017
Activity of Isavuconazole and Comparator Agents Against Pediatric Isolates From Invasive Fungal Infections
Marisa L Winkler1, Paul Rhomberg1, Kelley Fedler1
1Element Iowa City (JMI Laboratories), North Liberty, IA 52317, United States.
Background:
Invasive fungal infections (IFIs) 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 are lacking, which limits empiric treatment. We describe in vitro antifungal susceptibility testing of 900 contemporary yeast and mold isolates collected from IFIs in patients ≤ 17 years of age as a part of the SENTRY Antifungal Surveillance Program.
Methods:
A total of 900 isolates (743 yeasts and 157 molds) were collected from 28 countries between 2017 and 2024. Antifungal susceptibility testing was performed by broth microdilution according to Clinical and Laboratory and Standards Institute (CLSI) methodology.
Results:
A total of 33.4% of isolates were from patients ≤ 1 year old, 22.1% from patients aged 2-5 years old, 24.4% from patients aged 6-12 years old, and 20.0% from patients aged 13-17 years old. In total, 63.0% of yeasts were recovered from patients ≤ 5 years old; 79.6% of molds were from 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 isolates were susceptible to voriconazole and isavuconazole, respectively. Against Mucorales, the isavuconazole minimum inhibitory concentration (MIC)50 value was 4 mg/L, whereas the MIC50 values for voriconazole and posaconazole were > 8 mg/L. All agents had low MICs against most yeasts collected and there were few resistant or non-wildtype yeasts.
Conclusions:
Broth microdilution among a diverse collection of isolates obtained from IFIs 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. These data can guide the antifungal treatment of IFIs in pediatric patients when susceptibility testing is unavailable.
Insights
Invasive fungal infections in children show low resistance to common antifungals like azoles and echinocandins. Voriconazole and isavuconazole demonstrated excellent activity against yeast and Aspergillus species, guiding pediatric antifungal treatment.
Area of Science:
- Medical Microbiology
- Pediatric Infectious Diseases
- Antifungal Surveillance
Background:
- Invasive fungal infections (IFI) pose a growing threat to pediatric patients.
- Limited in vitro antifungal susceptibility data for pediatric isolates hinders effective empiric treatment.
- The SENTRY Antifungal Surveillance Program addresses this gap by analyzing pediatric fungal isolates.
Purpose of the Study:
- To characterize antifungal susceptibility profiles of contemporary yeast and mold isolates from pediatric patients with IFI.
- To provide crucial in vitro data to guide antifungal therapy selection in children.
- To assess the activity of key antifungal agents against a diverse collection of pediatric fungal pathogens.
Main Methods:
- Collected 900 yeast and mold isolates from invasive fungal infections in pediatric patients (≤17 years) across 28 countries (2017-2024).
- Performed in vitro antifungal susceptibility testing (AFST) using broth microdilution (BMD) according to Clinical Laboratory and Standards Institute (CLSI) guidelines.
- Analyzed isolate demographics, infection sources, and pathogen distribution by age group.
Main Results:
- Isolates represented diverse age groups, with yeasts predominantly from younger children (≤5 years) and molds from older children (≥6 years).
- Bloodstream infections were the primary source for yeasts, while respiratory tract infections were most common for molds.
- High susceptibility rates were observed for Aspergillus fumigatus against voriconazole and isavuconazole; isavuconazole showed good activity against Mucorales. Most yeasts exhibited low minimum inhibitory concentrations (MICs) to tested agents.
Conclusions:
- Broth microdilution testing of 900 pediatric fungal isolates revealed low resistance rates to echinocandins and azoles.
- Voriconazole and isavuconazole displayed the lowest MICs against yeasts, while triazoles were highly active against Aspergillus spp.
- Isavuconazole, posaconazole, and amphotericin B were most effective against non-Aspergillus molds, providing valuable data for pediatric IFI treatment.
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