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The impact of azole resistance on aspergillosis guidelines

Sarah P Georgiadou1, Dimitrios P Kontoyiannis

  • 1Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Annals of the New York Academy of Sciences
|December 13, 2012
PubMed

Insights

Azole resistance in Aspergillus species is increasing, impacting invasive aspergillosis treatment. Resistance, primarily due to CYP51A mutations, makes isolates itraconazole resistant, posing clinical challenges.

Area of Science:

  • Medical Mycology
  • Antifungal Resistance
  • Clinical Microbiology

Background:

  • Azole resistance in Aspergillus species presents a growing threat to managing invasive aspergillosis.
  • The primary mechanism involves alterations in the target enzyme, cytochrome P450 lanosterol 14α-demethylase (CYP51A).
  • Resistance can be primary or secondary, arising from single or multiple mutations.

Purpose of the Study:

  • To provide a comprehensive overview of current knowledge regarding azole resistance in Aspergillus species.
  • To highlight the implications of azole resistance for invasive aspergillosis management.
  • To identify areas for future research and practical considerations.

Main Methods:

  • Review of existing literature on azole resistance mechanisms in Aspergillus.
  • Analysis of studies reporting prevalence and characteristics of azole-resistant Aspergillus isolates.
  • Discussion of diagnostic challenges, including low fungal culturability.

Main Results:

  • Azole resistance in Aspergillus species is a significant concern with potential clinical implications.
  • Alterations in CYP51A are the main drivers of azole resistance in Aspergillus fumigatus.
  • All azole-resistant Aspergillus isolates demonstrate itraconazole resistance, regardless of specific CYP51A mutations.
  • Prevalence data is highly variable and exact frequencies remain unknown due to diagnostic limitations.

Conclusions:

  • Azole resistance in Aspergillus is an evolving challenge requiring ongoing surveillance and research.
  • Understanding resistance mechanisms is crucial for effective treatment strategies against invasive aspergillosis.
  • Further research is needed to address diagnostic gaps and refine clinical management protocols for azole-resistant infections.

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