Khojasteh Shaghayegh, Abastabar Mahdi, Haghani Iman, Valadan Reza, Ghazanfari Sahar, Abbasi Kiana, Ahangarkani Fatemeh, Zarrinfar Hossein, Khodavaisy Sadegh, Badali Hamid
Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.
Mycoses. 2023 Feb;66(2):98-105. doi: 10.1111/myc.13535. Epub 2022 Oct 17.
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.
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.
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.
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.
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.
侵袭性曲霉病是最常见的真菌感染之一，烟曲霉唑类耐药（ARAf）在高危患者中日益引起医学关注。据我们所知，伊朗尚无关于ARAf分离株流行率和发病率的全面流行病学监测研究。
本研究旨在报告一项为期五年的关于伊朗临床和环境中烟曲霉耐药性的三唑类表型和基因型模式的调查。
在研究时间段（2016 - 2021年）内，共收集了1208株临床和环境曲霉菌种。通过体外抗真菌药敏试验（CLSI M38肉汤微量稀释法）和cyp51A测序对分离株进行检测和鉴定。
总共分离出485株烟曲霉属菌株（临床分离株，n = 23；4.74%，环境分离株，n = 462；95.26%）。其中烟曲霉分离株是最常见的菌种（n = 483；99.59%）。与三唑类药物相比，两性霉素B和棘白菌素对大多数分离株表现出良好的体外活性。总体而言，16.15%（n = 78）的分离株对至少一种唑类药物表现出表型耐药。然而，伏立康唑的烟曲霉分离株中9.73%被归类为耐药，89.03%为敏感，1.24%为中介。对于伊曲康唑和泊沙康唑，分别使用流行病学临界值时，16.15%和6.83%的分离株为非野生型。值得注意的是，在21.79%（n = 17）表型耐药的分离株中，cyp51A基因未检测到突变。
虽然ARAf的发病率因国家而异，但在伊朗，该发病率在3.3%至18%之间变化，2013年至2021年显著上升。令人惊讶的是，四分之一的表型耐药分离株在cyp51A基因中没有突变。似乎其他耐药机制正在显著增加。为了填补我们对非cyp51A菌株唑类耐药机制理解上的空白，我们强烈建议对农业和医院区域中接触或未接触杀真菌剂的土壤进行进一步更广泛的监测。
