Prevalence and mechanisms of azole resistance in clinical isolates of Aspergillus section Fumigati species in a Canadian tertiary care centre, 2000 to 2013

J Antimicrob Chemother. 2020 Apr 1;75(4):849-858. doi: 10.1093/jac/dkz534.


Objectives: Azole resistance among Aspergillus fumigatus isolates is a growing concern worldwide. Induction of mutations during azole therapy, environment-acquired mutations caused by azole fungicides and intrinsic resistance of cryptic Fumigati species all contribute to the burden of resistance. However, there is a lack of data in Canada on this emerging threat.

Methods: To gain insights into the magnitude and mechanisms of resistance, a 14 year collection of Aspergillus section Fumigati comprising 999 isolates from 807 patients at a Montreal hospital was screened for azole resistance, and resistance mechanisms were investigated with the combined use of genome sequencing, 3D modelling and phenotypic efflux pump assays.

Results: Overall azole resistance was low (4/807 patients; 0.5%). A single azole-resistant A. fumigatus sensu stricto strain, isolated from a patient with pulmonary aspergillosis, displayed efflux-pump-mediated resistance. Three patients were colonized or infected with azole-resistant cryptic Fumigati species (one Aspergillus thermomutatus, one Aspergillus lentulus and one Aspergillus turcosus). Evidence is presented that azole resistance is efflux-pump-mediated in the A. turcosus isolate, but not in the A. lentulus and A. thermomutatus isolates.

Conclusions: Azole resistance is rare in our geographic area and currently driven by cryptic Fumigati species. Continued surveillance of emergence of resistance is warranted.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / pharmacology
  • Antifungal Agents / therapeutic use
  • Aspergillus / genetics
  • Aspergillus fumigatus / genetics
  • Azoles* / pharmacology
  • Canada
  • Drug Resistance, Fungal*
  • Fungal Proteins / genetics
  • Humans
  • Microbial Sensitivity Tests
  • Prevalence
  • Tertiary Care Centers


  • Antifungal Agents
  • Azoles
  • Fungal Proteins

Supplementary concepts

  • Aspergillus lentulus
  • Aspergillus thermomutatus
  • Aspergillus turcosus