Antifungal susceptibility of Aspergillus sp., Scedosporium sp. and Exophiala sp. isolated from patients with cystic fibrosis

BRITO DEVOTO T; POLA S; RUBEGLIO E; FINQUELIEVICH JL; GAMARRA S; GARCIA-EFFRON G; CUESTAS ML

Congreso; XVIII Congreso SADI; 2018

Moulds are frequently recovered from respiratory samples of cystic fibrosis (CF) patients. During the last decade, antifungal resistance in non-Candida species is increasingly reported. Azole resistance in Aspergillus fumigatus is a well-known problem and it was firstly reported in 1997 in three itraconazole-resistant clinical isolates. Since then, the main azole resistance mechanism reported are mutations at the CYP51A gene which encodes the azole drug target, the 14-α-sterol demethylase. The aims of this study were to overview the susceptibility profile from different fungal species isolated from respiratory secretions of Argentinean CF patients and to describe the molecular mechanisms of azole resistance in the isolated Aspergillus fumigatus strains. Amphotericin B, itraconazole, posaconazole and voriconazole minimum inhibitory concentrations (MICs) for 41 fungal strains: 34 Aspergillus spp. (22 A. fumigatus, 3 Aspergillus flavus, 2 Aspergillus niger, 6 Aspergillus terreus and 1 Aspergillus lentulus), 6 Scedosporium spp. (4 Scedosporium apiospermum and 2 Scedosporium auarnticum) and 1 Exophiala dermatitidis recovered from 20 CF patients were determined by using the CLSI M38-A2 document and Etest. The study of the azole mechanism of resistance in A. fumigatus, the full CYP51A coding sequences and its 5´UTR regions were amplified and sequenced. For amphotericin B, MICs were above the epidemiological cut-off values (ECV) in 100% of A. lentulus, 100% of S. auranticum and 50% of S. apiospermum. For voriconazole, MICs were above the ECV in 4.5% of A. fumigatus, 16.7% of A. terreus and 100% of A. lentulus. For posaconazole, MICs were above the ECV in 13.6% of A. fumigatus and 100% A. lentulus. For itraconazole, MICs were above the ECV in 13.6% A. fumigatus, 100% A. lentulus, 75% S. apiospermum and 100% S. auranticum. Three A. fumigatus strains showing mutations in their CYP51A genes were isolated.Azole drugs are one of the few therapeutic options to treat invasive fungal infections. The emergence of resistance is a problem that should be continuously monitored specially in CF patients.