title: High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: is it a challenging issue?
abstract: Triazole antifungal agents are the mainstay of aspergillosis treatment. As highlighted in numerous studies, the global increase in the prevalence of triazole resistance could hamper the management of aspergillosis. In the present three-year study, 513 samples (213 clinical and 300 environmental samples) from 10 provinces of Iran were processed and screened in terms of azole resistance (4 and 1 mg l-1 of itraconazole and voriconazole, respectively), using selective plates. Overall, 150 A. fumigatus isolates (71 clinical and 79 environmental isolates) were detected. The isolates were confirmed by partial sequencing of the β-tubulin gene. Afterwards, in vitro antifungal susceptibility tests against triazole agents were performed, based on the Clinical and Laboratory Standards Institute (CLSI) M38-A2 document. The CYP51A gene was sequenced in order to detect mutations. The MIC of itraconazole against 10 (6.6 %) strains, including clinical (n=3, 4.2 %) and environmental (n=7, 8.8 %) strains, was higher than the breakpoint and epidemiological cut-off value. Based on the findings, the prevalence of azole-resistant A. fumigatus in Iran has increased remarkablyfrom 3.3 % to 6.6 % in comparison with earlier epidemiological research. Among resistant isolates, TR34/L98H mutations in the CYP51A gene were the most prevalent (n=8, 80 %), whereas other point mutations (F46Y, G54W, Y121F, G138C, M172V, F219C, M220I, D255E, T289F, G432C and G448S mutations) were not detected. Although the number of patients affected by azole-resistant A. fumigatus isolates was limited, strict supervision of clinical azole-resistant A. fumigatus isolates and persistent environmental screening of azole resistance are vital to the development of approaches for the management of azole resistance in human pathogenic fungi.
authors.affiliation: Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Nabili
authors.affiliation: Department of Medical Mycology and Parasitology, Invasive Fungi Research Center, School of Medicine Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Tahereh
authors.initials: T
authors.lastname: Shokohi
authors.affiliation: Department of Medical Mycology and Parasitology, Invasive Fungi Research Center, School of Medicine Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Moazeni
authors.affiliation: Department of Medical Mycology and Parasitology, Kurdistan University of Medical Sciences, Sanandaj, Iran.|Department of Medical Mycology and Parasitology, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sadegh
authors.initials: S
authors.lastname: Khodavaisy
authors.affiliation: Department of Internal Medicine, Pulmonary and Critical Care Division, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Aliyali
authors.affiliation: Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Parisa
authors.initials: P
authors.lastname: Badiee
authors.affiliation: Allergy Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Zarrinfar
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
authors.forename: Ferry
authors.initials: F
authors.lastname: Hagen
authors.affiliation: Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.|Department of Medical Mycology and Parasitology, Invasive Fungi Research Center, School of Medicine Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Badali
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D001228:Aspergillosis / Q000453:epidemiology* / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D007492:Iran / Q000453:epidemiology; D017964:Itraconazole / Q000494:pharmacology*; D009154:Mutation; D015995:Prevalence; 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