Aspergillus fumigatus variant with decreased susceptibility to multiple antifungals

S Arunmozhi Balajee1, Molly Weaver, Alexander Imhof

  • 1Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.

Insights

Antifungal resistance in Aspergillus fumigatus is a growing concern. This study identified a unique, poorly sporulating A. fumigatus variant with reduced susceptibility to multiple antifungals, including itraconazole.

Area of Science:

  • Medical Mycology
  • Infectious Diseases
  • Antimicrobial Resistance

Background:

  • Itraconazole (ITZ) resistance in Aspergillus fumigatus is known but not fully understood.
  • Invasive fungal infections pose significant risks, especially in immunocompromised patients like stem cell transplant recipients.

Purpose of the Study:

  • To assess the prevalence and clinical significance of ITZ resistance in A. fumigatus isolates from stem cell transplant patients.
  • To characterize unusual A. fumigatus isolates exhibiting reduced antifungal susceptibility.

Main Methods:

  • Antifungal susceptibility testing (MICs) for ITZ, voriconazole, caspofungin, and amphotericin B.
  • Phenotypic characterization including colony morphology and sporulation.
  • Molecular typing using randomly amplified polymorphic DNA-PCR and gene sequencing (18S rRNA, mitochondrial cytochrome b).

Main Results:

  • 10 of 128 A. fumigatus isolates showed high ITZ MICs (>1 µg/ml).
  • Seven atypical isolates with high ITZ MICs displayed a distinct white colony phenotype due to slow sporulation.
  • These atypical isolates also exhibited high MICs for voriconazole and caspofungin, and in some cases, amphotericin B.
  • Molecular analysis revealed unique mitochondrial cytochrome b gene sequences in the atypical isolates, suggesting a distinct genetic variant.

Conclusions:

  • A genetically unique, poorly sporulating variant of A. fumigatus may be emerging.
  • This variant demonstrates decreased susceptibility to multiple antifungal agents.
  • Further research is needed to understand the prevalence and clinical impact of this antifungal-resistant A. fumigatus variant.

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