Five-Year Surveillance Study of Clinical and Environmental Triazole-Resistant Aspergillus Fumigatus Isolates in Iran Publisher Pubmed



Khojasteh S^{1, 2} ; Abastabar M^{1, 2} ; Haghani I^{1, 2} ; Valadan R³ ; Ghazanfari S⁴ ; Abbasi K⁵ ; Ahangarkani F⁶ ; Zarrinfar H⁷ ; Khodavaisy S⁸ ; Badali H^{1, 2, 9} Show Affiliations
Source: Mycoses Published:2023

Abstract

Background: Invasive aspergillosis is one of the most common fungal infections and azole resistance in Aspergillus fumigatus (ARAf) is a growing medical concern in high-risk patients. To our knowledge, there is no comprehensive epidemiological surveillance study on the prevalence and incidence of ARAf isolates available in Iran. Objectives: The study aimed to report a five-year survey of triazole phenotypes and genotype patterns concerning the resistance in clinical and environmental A. fumigatus in Iran. Methods: During the study time frame (2016–2021), a total of 1208 clinical and environmental Aspergillus species were collected. Isolates were examined and characterised by in vitro antifungal susceptibility testing (CLSI M38 broth microdilution) and cyp51A sequencing. Results: In total, 485 Aspergillus section Fumigati strains were recovered (clinical, n = 23; 4.74% and environment, n = 462; 95.26%). Of which A. fumigatus isolates were the most prevalent species (n = 483; 99.59%). Amphotericin B and the echinocandins demonstrated good in vitro activity against the majority of isolates in comparison to triazole. Overall, 16.15% (n = 78) of isolates were phenotypically resistant to at least one of the azoles. However, 9.73% of A. fumigatus isolates for voriconazole were classified as resistant, 89.03% were susceptible, and 1.24% were intermediate. While, for itraconazole and posaconazole, using the epidemiological cut-off value 16.15% and 6.83% of isolates were non-wild types, respectively. Remarkably, in 21.79% (n = 17) phenotypically resistant isolates, no mutations were detected within the cyp51A gene. Conclusion: Although the incidence of ARAf varies from country to country, in Iran the rate has ranged from 3.3% to 18%, significantly increasing from 2013 to 2021. Strikingly, a quarter of the phenotypically resistant isolates harboured no mutations in the cyp51A gene. It seems that other mechanisms of resistance are importantly increasing. To fill a gap in our understanding of the mechanism for azole resistance in the non-cyp51A strains, we highly recommend further and more extensive monitoring of the soil with or without exposure to fungicides in agricultural and hospital areas. © 2022 Wiley-VCH GmbH.