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Azole resistance in Aspergillus fumigatus: a growing public health concern

Edith Vermeulen1, Katrien Lagrou, Paul E Verweij

  • 1aDepartment of Microbiology and Immunology, Catholic University of Leuven bDepartment of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium cDepartment of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.

Current Opinion in Infectious Diseases
|October 16, 2013
PubMed
Abstract

Insights

Azole resistance in Aspergillus fumigatus is a growing global health concern. Environmental and patient-derived resistant strains, like TR34/L98H, are increasingly reported worldwide, necessitating further research and data collection.

Area of Science:

  • Medical Mycology
  • Antimicrobial Resistance
  • Fungal Pathogenesis

Background:

  • Azole resistance in Aspergillus fumigatus emerged as a significant clinical concern in the late 2000s.
  • Both chronically treated and azole-naive patients are at risk due to resistant environmental strains.
  • Understanding the origin and evolution of resistance is crucial for managing invasive fungal infections.

Purpose of the Study:

  • To review the latest findings on the origin, evolution, and implications of azole resistance in Aspergillus fumigatus.
  • To highlight the increasing prevalence and geographical spread of resistant strains.
  • To discuss emerging resistance mechanisms and the need for better data management.

Main Methods:

  • Literature review of recent epidemiological and molecular studies on azole resistance in A. fumigatus.
  • Analysis of reported resistance mechanisms, including CYP51A-mediated and non-CYP51A-mediated pathways.
  • Synthesis of data on the geographical distribution and genotypic variations of resistant isolates.

Main Results:

  • TR34/L98H is the predominant environmental resistance mechanism, with expanding reports globally.
  • Genotypic differences exist between Middle Eastern and European TR34/L98H strains, suggesting independent emergence.
  • A novel environmental resistance mechanism, TR46/Y121F/T289A, confers voriconazole resistance.
  • Patient resistance mechanisms are diversifying beyond CYP51A-mediated pathways.

Conclusions:

  • Azole resistance in Aspergillus fumigatus is a rapidly evolving global health problem.
  • Continuous monitoring and characterization of resistant strains are essential.
  • Centralized registration of treatment and outcome data for patients with resistant aspergillosis is needed.

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