P039 Cross-resistance to clinical and agricultural azoles among <i>Aspergillus fumigatus</i> strains isolated from humans and environment in Italy

Abstract Poster session 1, September 21, 2022, 12:30 PM - 1:30 Objectives In Italy, a prevalence of 16.9% resistance to clinical azoles was observed among Aspergillus fumigatus isolates from an agricultural environment. This spread azole-resistance is attributed the widespread use 14a-demethylase inhibitors (DMIs). The aims present study were investigate: DMIs in Italian A. strains and environmental origin, both susceptible resistant azoles; molecular mechanism but at least one tested DMIs; vitro DMI induced by prolonged exposure strains, resistance. Methods A total 54 selected: 23 (CAS) 31 (CAR) with without mutations CYP51A gene (TR34/L98H, F219I, G54R, G54E, D269Y, M220I, or F46Y/M172V/N248T/D255E/E427K). Antifungal susceptibility testing performed for 8 (tebuconazole, epoxiconazole, difenoconazole, propiconazole, tetraconazole, flusilazole, fenbuconazole, prochloraz) using broth microdilution method according EUCAST CLSI methods. Mutations CYP51A, CYP51B, HMG1 genes investigated CAS high MIC values. induction on 11 (6 5 environmental) DMIs. suspension 106 conidia inoculated glucose-yeast extract-peptone agar plates containing different concentrations incubated 37°C 72 h six repeated passages. Results Comparable results obtained Resistance (MIC ≥16) tetraconazole fenbuconazole 100% isolates, CAR CAS. On contrary, statistically significant difference tebuconazole, flusilazole MICs between higher geometric means (GM) (range 4.9-9.3 mg/L) than (1.5-2.7 strains. Prochloraz showed lowest GMs: 0.6 0.25 mg/L respectively. GMs all tested, except prochloraz, harboring TR34/L98H M220I mutation (GM range 10.4-16 those other 1-4.6 mg/L). showing MICs, absence confirmed, while synonymous P394P, identified CYP51B. No found. tests, phenotypic (11/11 isolates) 72.7% (8/11) 54% (6/11) tebuconazole 9.1% (1/11) prochloraz. Molecular analysis understand if corresponds progress. Conclusions Preliminary confirm cross-resistance DMIs, differences gene. Furthermore, ability induce highlighted.