title: Azole susceptibility in clinical and environmental isolates of Aspergillus fumigatus from eastern Hokkaido, Japan.
abstract: Azole antifungals are used not only clinically for fungal infections but also used as agricultural fungicides. Recently, azole-resistant Aspergillus fumigatus containing a tandem repeat in the promoter region of cyp51A combined with amino acid substitution(s) appears in the environment in Eurasia, especially in several European countries. Although azole fungicides have been used in Japan, especially in Hokkaido, surveillance and characterization of A. fumigatus in Hokkaido have not been reported. In this study, we collected soil samples from farms that used an azole fungicide in the Tokachi area of eastern Hokkaido, isolated 91 A. fumigatus strains, and determined the minimal inhibitory concentrations of medical azoles required for these strains. Moreover, because causative agent A. fumigatus is ubiquitous in the air and acquired from the environment, we collected 22 clinical isolates of A. fumigatus to measure their susceptibility to medical azoles in a hospital in the Tokachi area. Our data show that almost all A. fumigatus isolates retained susceptibility to medical azoles. Clinical isolates OKH34 and OKH6 showed 8 and 2 μg/mL of voriconazole, respectively, as the minimal inhibitory concentration. Both isolates did not contain tandem repeat in cyp51A promoter region. An isolate contained G448S mutation in cyp51A conferring voriconazole resistance, which is the first report from Japan. Our data shows the existence of azole-resistant and low azole-susceptible clinical isolates and highlight the necessity for continuous surveillance in Japan because resistant A. fumigatus strains can arise through clinical or environmental selection or could be introduced from overseas.
authors.affiliation: Diagnostic Center for Animal Health and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-11, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan; Division of Clinical Research, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba, 260-8673, Japan. Electronic address: tome@obihiro.ac.jp.
authors.forename: Takahito
authors.initials: T
authors.lastname: Toyotome
authors.affiliation: Diagnostic Center for Animal Health and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-11, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Department of Medical Technologist, Obihiro-Kosei General Hospital, West 6 South 8-1, Obihiro, Hokkaido, 080-0016, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kida
authors.affiliation: First Department of Internal Medicine, Obihiro-Kosei General Hospital, West 6 South 8-1, Obihiro, Hokkaido, 080-0016, Japan.
authors.forename: Munehiro
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Medical Technologist, Obihiro-Kosei General Hospital, West 6 South 8-1, Obihiro, Hokkaido, 080-0016, Japan.
authors.forename: Terumi
authors.initials: T
authors.lastname: Wada
authors.affiliation: Department of Medical Technologist, Obihiro-Kosei General Hospital, West 6 South 8-1, Obihiro, Hokkaido, 080-0016, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Komatsu
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000235:genetics; D005656:Fungal Proteins / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D007564:Japan; D008826:Microbial Sensitivity Tests; D009154:Mutation; D065819:Voriconazole / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D017964:Itraconazole; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus; D065819:Voriconazole
keywords: Aspergillus fumigatus; Azole; cyp51A