AR RIAT¹, FI ISCHER³, JC SCHRENZEL², KG GINDRO⁴, DS SANGLARD<sup>3

1</sup>Bacteriology Laboratory, University of Geneva Hospitals, , ²Genomic Research Laboratory, Service of Infectious Diseases, University of Geneva Hospitals and Faculty of Medicine; Geneva (Switzerland), ³Institute of Microbiology, University Hospital Lausanne and University Hospital Center, CH-1011 Lausanne, Switzerland, ⁴Agroscope, Institute for Plant Production Sciences IPS, Mycology and Biotechnology, 1260 Nyon, Switzerland.

Abstract
Aspergillus fumigatus isolates resistant to azole drugs have been reported in several countries, however no recent data exist in Switzerland.
Snelders and colleagues (1) have described azoles resistance in A. fumigatus isolated from clinical samples for the first time in 2008. The mutations found in the azole-resistant isolates were associated with the gene CYP51A, whose product is involved in ergosterol biosynthesis. Different codon substitutions in CYP51A have been identified from A. fumigatus in clinical samples as well as samples from the environment. The presence of A. fumigatus with a single substitution in CYP51A is mainly encountered in patients after long-term azole therapy. In addition to single mutations, a tandem repeat in the promoter region of the CYP51A has been identified and was found to confer multi-azole resistance (TR34/L98H and TR46/Y121F/T289A)(2). Different studies have suggested an environmental origin of the TR34/L98H and TR46/Y121F/T289A mutations with a predominance of TR34/L98H (3, 4).
Here, we describe the first environmental A. fumigatus isolates, which harbored CYP51A mutations that confer azole resistance. Sixty-nine samples were collected in the Geneva Lake area and four of them showed resistance to azoles drugs. Three isolates possessed the TR34/L98H mutation and one isolate had a single substitution at the position 54 (G54R) of CYP51A. In addition, 20 A. fumigatus isolated from cystic fibrosis patients during the year 2011 and 2015 were phenotypically tested for azole resistance, however all of them were susceptible to itraconazole.
In conclusion, the occurrence of azole resistance from environmental origin in Switzerland is in agreement with reports from other countries. This situation needs further systematic surveillance, since transmission of azole-resistant isolates to patients is possible.