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Azole preexposure affects the Aspergillus fumigatus population in patients

Alexandre Alanio1, Odile Cabaret, Emilie Sitterlé

  • 1Institut Pasteur, Unité de mycologie moléculaire, Paris, France.

Antimicrobial Agents and Chemotherapy
|June 20, 2012
PubMed

Insights

Voriconazole preexposure in patients selects for Aspergillus fumigatus isolates with specific CYP51A gene mutations. These mutations are linked to higher itraconazole minimum inhibitory concentrations (MICs).

Area of Science:

  • Medical Mycology
  • Antifungal Resistance
  • Clinical Microbiology

Background:

  • Azole antifungals are crucial for treating Aspergillus fumigatus infections.
  • Emergence of azole resistance in A. fumigatus is a significant clinical concern.
  • CYP51A gene polymorphisms are a known mechanism of azole resistance.

Purpose of the Study:

  • To investigate the impact of patient azole preexposure on A. fumigatus isolate characteristics.
  • To correlate CYP51A polymorphisms with azole susceptibility and genetic clustering.
  • To understand the selection pressures exerted by voriconazole preexposure.

Main Methods:

  • Analysis of 110 A. fumigatus isolates from 86 patients with known azole preexposure history.
  • Genotyping of isolates to identify CYP51A polymorphisms.
  • Determination of azole susceptibility using EUCAST methodology, including itraconazole and voriconazole.
  • Phylogenetic analysis to identify genetic clusters.

Main Results:

  • Isolates with specific CYP51A polymorphisms (F46Y, M172V, N248T, D255E, E427K) exhibited higher itraconazole MICs (P = 0.04).
  • These polymorphic isolates were associated with two distinct genetic clusters (P < 0.001).
  • Voriconazole preexposure was significantly linked to the selection of these A. fumigatus isolates (P = 0.016).

Conclusions:

  • Patient voriconazole preexposure drives the selection of A. fumigatus isolates harboring CYP51A polymorphisms.
  • These selected isolates demonstrate reduced susceptibility to itraconazole.
  • Understanding these selection dynamics is vital for optimizing antifungal treatment strategies.

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