The prevalence of azole-resistant Aspergillus fumigatus (ARAF) among chronic pulmonary aspergillosis (CPA) patients treated with azoles in Japan is unknown. The aim of this study was to determine the detection rate of ARAF in isolates from CPA patients who were treated with azoles for varying durations. The potential mechanism of acquiring resistance was examined by sequencing cyp51A and hmg1, two genes associated with ARAF. A. fumigatus isolates (n = 120) were collected from CPA patients (n = 104) between February 2012 and February 2019, at National Hospital Organization Tokyo National Hospital. The isolates were tested for susceptibility to the azole drugs itraconazole (ITCZ) and voriconazole (VRCZ). The detection rate of ARAF among all isolates was 8.3% (n = 10). Of the 10 resistant isolates, eight were ITCZ-resistant and five were VRCZ-resistant. Among 47 isolates obtained from 36 CPA patients who were treated with ITCZ (for an average of 256 days) and/or VRCZ (for an average of 29 days), the resistance rates were 17.0% and 10.6%, respectively. In addition, 46.2% of 13 isolates obtained from CPA patients with ongoing azole treatment at the time of antifungal therapy failure were resistant to azoles. Among the 10 ARAF isolates, a point mutation was detected in cyp51A in seven isolates and in hmg1 in two isolates. ARAF was detected at a high rate in CPA patients, particularly in those with ongoing long-term azole treatment, at the time of azole antifungal therapy failure.

中文翻译：

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低唑类耐药单医院慢性肺曲霉病患者经唑类抗真菌药物治疗后耐药烟曲霉检出率高

在日本接受唑类药物治疗的慢性肺曲霉病 (CPA) 患者中，唑类耐药的烟曲霉(ARAF)的患病率尚不清楚。本研究的目的是确定在接受不同持续时间唑类治疗的 CPA 患者的分离株中 ARAF 的检出率。通过对与ARAF相关的两个基因cyp51A和hmg1进行测序来检查获得抗性的潜在机制。烟曲霉分离物（Ñ  = 120）从CPA患者采集（Ñ = 104) 2012 年 2 月至 2019 年 2 月，在国立医院组织东京国立医院。对这些分离株进行了对唑类药物伊曲康唑 (ITCZ) 和伏立康唑 (VRCZ) 的敏感性测试。所有分离株中ARAF的检出率为8.3%（n  =10）。在 10 个耐药菌株中，8 个对 ITCZ 耐药，5 个对 VRCZ 耐药。在从接受 ITCZ（平均 256 天）和/或 VRCZ（平均 29 天）治疗的 36 名 CPA 患者中获得的 47 株分离物中，耐药率分别为 17.0% 和 10.6%。此外，在抗真菌治疗失败时从接受唑类药物治疗的 CPA 患者中获得的 13 株分离物中，有 46.2% 对唑类药物耐药。在 10 个 ARAF 分离株中，在cyp51A中检测到点突变在七个分离株中和在两个分离株中的hmg1。在唑类抗真菌治疗失败时，在 CPA 患者中检测到 ARAF 的比率很高，特别是在那些正在进行长期唑类治疗的患者中。