High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: Is it a challenging issue?

Nabili, M. and Shokohi, T. and Moazeni, M. and Khodavaisy, S. and Aliyali, M. and Badiee, P. and Zarrinfar, H. and Hagen, F. and Badali, H. (2016) High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: Is it a challenging issue? Journal of Medical Microbiology, 65 (6). pp. 468-475.

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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 theCYP51A 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. © 2016 The Authors.

Item Type: Article
Additional Information: Cited By :21 Export Date: 16 February 2020 CODEN: JMMIA Correspondence Address: Badali, H.; Pharmaceutical Sciences Research Center, Mazandaran University of Medical SciencesIran; email: badalii@yahoo.com
Uncontrolled Keywords: A. fumigatus Iran TR34/L98H mutation Triazole-resistant amphotericin B beta tubulin caspofungin itraconazole posaconazole pyrrole triazole voriconazole antifungal agent cytochrome P-450 CYP51A, Aspergillus cytochrome P450 fungal protein antifungal resistance antifungal susceptibility Article Aspergillus fumigatus CYP51A gene fungal gene fungus isolation gene mutation gene sequence in vitro study minimum effective concentration minimum inhibitory concentration nonhuman prevalence priority journal aspergillosis dna mutational analysis drug effects gene expression regulation genetics human metabolism microbiology multidrug resistance mutation Antifungal Agents Cytochrome P-450 Enzyme System Drug Resistance, Multiple, Fungal Fungal Proteins Gene Expression Regulation, Enzymologic Gene Expression Regulation, Fungal Humans
Subjects: WC Communicable Diseases
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib4 lib4
Date Deposited: 01 Mar 2020 07:04
Last Modified: 01 Mar 2020 07:04
URI: http://eprints.mums.ac.ir/id/eprint/13118

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