Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM), Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Científicas y Tecnológicas, Argentina.
Mycoses. 2020 Sep;63(9):937-941. doi: 10.1111/myc.13139. Epub 2020 Aug 7.
Triazole resistance in Aspergillus fumigatus sensu stricto due to mutations in the cyp51A gene has been widely reported. Data from Argentina, and particularly from cystic fibrosis (CF) patients, are limited.
To investigate the prevalence and molecular mechanisms of azole resistance in A. fumigatus sensu stricto recovered from this population.
Ninety-three A. fumigatus isolates from 50 CF patients were retrospectively analysed for azole resistance using the standard microbroth dilution method according to CLSI M38-A2 guidelines. Sequencing analysis of the cyp51A gene and its promoter region was conducted in those isolates displaying high MIC values to itraconazole, voriconazole and/or posaconazole.
Overall, 14% of isolates displayed high MIC values to at least one azole. Of them, 30.7% had the mutation TR34-L98H. No mutations in the cyp51A gene or its promoter were found in the remaining non-wild-type strains. Therefore, other mechanisms associated with azole resistance can be highly prevalent in these isolates.
To the best of our knowledge, this is the first study in Latin America reporting azole-resistant A. fumigatus strains recovered from respiratory secretions of CF patients. Noteworthy, the prevalence of azole resistance in A. fumigatus sensu stricto in the studied Argentinean CF population is alarmingly high.
由于 cyp51A 基因突变，烟曲霉严格意义上的三唑类耐药已被广泛报道。来自阿根廷的数据，特别是来自囊性纤维化 (CF) 患者的数据十分有限。
调查从该人群中分离出的烟曲霉严格意义上对唑类药物耐药的流行情况和分子机制。
对 50 例 CF 患者的 93 株烟曲霉分离株进行回顾性分析，采用 CLSI M38-A2 指南规定的标准微量肉汤稀释法检测唑类药物耐药性。对显示伊曲康唑、伏立康唑和/或泊沙康唑 MIC 值较高的分离株进行 cyp51A 基因及其启动子区的测序分析。
总体而言，14%的分离株对至少一种唑类药物显示出高 MIC 值。其中，30.7%的菌株存在 TR34-L98H 突变。在其余非野生型菌株中未发现 cyp51A 基因或其启动子区的突变。因此，这些分离株中可能存在其他与唑类耐药相关的机制。
据我们所知，这是在拉丁美洲首次报道从 CF 患者呼吸道分泌物中分离出的对唑类药物耐药的烟曲霉菌株。值得注意的是，研究中阿根廷 CF 人群中烟曲霉严格意义上的唑类耐药率高得惊人。
