Azole and fungicide resistance in clinical and environmentalAspergillus fumigatusisolates

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Abstract
Aspergillus fumigatus is a human pathogen but it is also a widespread filamentous fungus in the environment. A. fumigatus can therefore be exposed to antifungals used in medical and agricultural environments. Only the class of azoles is used in both of these environments (i.e., voriconazole and itraconazole in medicine; prochloraz, propiconazole or imazalil in agriculture). Exposure to azoles provides the potential for the development of resistance. Several clinical itraconazole-resistant isolates have been reported in A. fumigatus and their resistance mechanisms have been partially resolved. Since limited data exist on the susceptibility of A. fumigatus to both medical and agricultural antifungals, we undertook a drug susceptibility study including clinical (400) and agricultural (150) A. fumigatus isolates (Swiss origin). We tested azoles and also compounds of major antifungal classes used in agriculture (i.e., azoxystrobin, iprodione, benalaxyl or cyprodinil). The results showed that all A. fumigatus isolates were intrinsically resistant to iprodione, benalaxyl or cyprodinil (MIC90>32 µg.ml−1) and that azoxystrobin minimal inhibitory concentrations (MICs) showed a wide range (0.06 to 32 µg.ml−1). MIC ranges of azoles were compound-dependent. MIC90 for voriconazole, itraconazole, imazalil and prochloraz were within a range of 0.125 to 1 µg.ml−1 and similar between clinical and environmental isolates, whereas propiconazole was the least active compound (MIC90: 4–8 µg.ml−1). Ten clinical and 36 environmental isolates with high itraconazole MIC (≥2 µg.ml−1) were detected. In clinical isolates, no cross-resistance was observed between itraconazole and all others azoles tested. Several patterns of azole MICs for were, however, observed in the environmental isolates. Unexpectedly, a single environmental isolate was voriconazole-resistant (MIC of 16 µg.ml−1) but still susceptible to itraconazole (MIC of 2 µg.ml−1). Taken together, our results demonstrate the absence of susceptibility of A. fumigatus isolates to non-azole agricultural agents and that there is little impact of azole resistance in both clinical and environmental isolates. When detected, azole resistance was compound-specific.

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