title: Azole-resistant Aspergillus fumigatus isolates carrying TR₃₄/L98H mutations in Taiwan.
abstract: Cumulative evidence described the emergence and geographical expansion of azole-resistant A. fumigatus associated with azole treatment failure. To investigate the status of azole resistance in A. fumigatus in Taiwan, we studied 38 A. fumigatus clinical isolates cultivated from 31 patients at two teaching hospitals from 2011 to 2014. Three isolates obtained from respiratory samples of two azole-naïve patients with pulmonary aspergillosis were found to display multi-azole resistance and cross resistance to agricultural azole fungicides, and all carried TR34/L98H mutations in cyp51A gene. The prevalence rates of azole resistance were 7.9% and 6.5% based on isolates and patients respectively. A phylogenetic analysis suggested genetic diversity of the TR34/L98H isolates in Taiwan, including a unique genotype distinct from strains outside Taiwan. The result underlines the emergence of such isolates in Taiwan as well, emphasising the importance of further surveillance for azole-resistant A. fumigatus and implementation of strategies that prevent fungicide-driven resistance selection.
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.|Department of Internal Medicine, National Cheng Kung University Hospital and Medical College, Tainan, Taiwan.
authors.forename: Chi-Jung
authors.initials: CJ
authors.lastname: Wu
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Hsuan-Chen
authors.initials: HC
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital and Medical College, Tainan, Taiwan.
authors.forename: Jen-Chieh
authors.initials: JC
authors.lastname: Lee
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Hsiu-Jung
authors.initials: HJ
authors.lastname: Lo
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Ching-Tzu
authors.initials: CT
authors.lastname: Dai
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Pei-Hsin
authors.initials: PH
authors.lastname: Chou
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital and Medical College, Tainan, Taiwan.
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Ko
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.|Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Yee-Chun
authors.initials: YC
authors.lastname: Chen
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D001393:Azoles; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010802:Phylogeny; D055732:Pulmonary Aspergillosis / Q000453:epidemiology / Q000382:microbiology; D012189:Retrospective Studies; D013624:Taiwan / Q000453:epidemiology; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D005656:Fungal Proteins; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus
keywords: Aspergillus fumigatus; Azole resistance; TR34/L98H; Taiwan; azole fungicide