Activity of isavuconazole and other triazole derivatives against clinical isolates of Aspergillus fumigatus

Abstract

Aspergillus fumigatus is the most frequent pathogen of the genus Asperillus, which is highly susceptible to triazole derivatives, especially to isavuconazole and voriconazole. Many countries face a growing problem of infections due to A. fumigatus showing acquired resistance to one or several triazoles. In medical centres, monitoring the susceptibility of isolated Aspergillus spp. is recommended. Aim: The aim of this study was to collect and test triazole susceptibility of Aspergillus fumigatus obtained from clinical samples, which were investigated in diagnostic laboratories located in Wrocław, Warszawa and Ruda Śląska (Poland). In addition, 5 resistant A. fumigatus strains with TR34/L98H mutation were included. Material/Methods: The microdilution method, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) was applied to test susceptibility to isavuconazole (ISV), voriconazole (VOR), posaconazole (POS) and itraconazole (ITR). Results: During a period of 24 months, a total number of 75 A. fumigatus isolates were collected. Most of the strains were obtained from lower respiratory tract specimens (58/75; 77%), from patients hospitalized on pulmonology (41%) or intensive care and surgery units (29%). No isolate resistant to ISV or other triazoles was found. The minimal inhibitory concentration (MIC) value of ISV ranged from 0.125 to 1 mg/L (mean 0.4 ±0.15 mg/L) in triazole susceptible isolates, whereas among triazole-resistant strains, three showed a MIC of 8 mg/L and two had a MIC of 4 mg/L. Conclusions: A. fumigatus isolates carrying the mutation TR34/L98H are cross-resistant to ISV. The acquired resistance is very rare in our region (0-4%), which supports of use of triazole derivatives (VOR, ISV) in the therapy of aspergillosis.