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Azole-resistance in Aspergillus: proposed nomenclature and breakpoints

Paul E Verweij1, Susan J Howard, Willem J G Melchers

  • 1Department of Medical Microbiology, Radboud University, Nijmegen Medical Centre, The Netherlands.

Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
|November 3, 2009
PubMed

Insights

Reports of itraconazole resistance in Aspergillus fumigatus are increasing. New breakpoints for azole antifungal susceptibility testing are proposed to guide treatment, alongside nomenclature for genotypic resistance.

Area of Science:

  • Medical Mycology
  • Antimicrobial Resistance

Background:

  • Increasing reports of itraconazole resistance in Aspergillus fumigatus since 2000.
  • Azole resistance identification is method-dependent, but reproducible methods are available.
  • Some Aspergillus isolates exhibit reduced susceptibility to posaconazole and voriconazole.

Purpose of the Study:

  • To propose clinical breakpoints for azole antifungal susceptibility testing in Aspergillus fumigatus.
  • To establish standardized nomenclature for genotypic azole resistance in Aspergillus.

Main Methods:

  • Utilized the proposed EUCAST susceptibility testing methodology.
  • Determined minimum inhibitory concentrations (MICs) for itraconazole, voriconazole, and posaconazole.
  • Proposed nomenclature for genotypic resistance, e.g., ITZgR, VCZgI, POSgR (G54W).

Main Results:

  • Proposed breakpoints for itraconazole and voriconazole: susceptible (<2 mg/L), intermediate (2 mg/L), resistant (>2 mg/L).
  • Proposed breakpoints for posaconazole: susceptible (<0.25 mg/L), intermediate (0.5 mg/L), resistant (>0.5 mg/L).
  • Identified multiple resistance mechanisms, including Cyp51A gene mutations (e.g., G54W), conferring cross-resistance.

Conclusions:

  • Proposed breakpoints require further validation with in vivo and clinical data.
  • Standardized breakpoints and genotypic nomenclature are crucial for managing azole-resistant Aspergillus infections.
  • Accurate susceptibility testing is vital for effective antifungal therapy in aspergillosis.

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