Diagnostic Mycology Service, Department of Medical Microbiology, North West London Pathology, Imperial College Healthcare National Health Service Trust, London, UK; Fungal Pathogens Laboratory, National Heart and Lung Institute, Imperial College London, UK.
Fungal Pathogens Laboratory, National Heart and Lung Institute, Imperial College London, UK; Department of Clinical Pharmacology, Guys and St Thomas' Foundation NHS Trust, London, UK.
Int J Antimicrob Agents. 2018 Nov;52(5):637-642. doi: 10.1016/j.ijantimicag.2018.08.004. Epub 2018 Aug 10.
To evaluate the prevalence of triazole-resistant Aspergillus fumigatus and common molecular cyp51A polymorphisms amongst clinical isolates in a specialised cardiothoracic centre in London, UK.
All A. fumigatus isolates were prospectively analysed from April 2014 to March 2016. Isolates were screened with a four-well VIPcheck™ plate to assess triazole susceptibility. Resistance was confirmed with a standard microbroth dilution method according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Triazole-resistant A. fumigatus isolates were subjected to a mixed-format real time polymerase chain reaction (RT-PCR) assay (AsperGenius) to detect common cyp51A alterations.
We identified 167 clinical A. fumigatus isolates from 135 patients. Resistance to at least one azole antifungal drug was confirmed in 22/167 (13.2%) of isolates from 18/135 (13.3%) patients, including 12/74 (16.2%) patients with cystic fibrosis (CF). The highest detection rate of azole-resistant A. fumigatus was among the 11- to 20-y age group. All triazole-resistant isolates (n = 22) were resistant to itraconazole, 18 showed cross-resistance to posaconazole and 10 displayed reduced susceptibility to voriconazole. No pan-azole-resistant A. fumigatus was identified. TR/L98H was identified in 6/22 (27.3%) of azole-resistant isolates and detectable in 5/12 (42%) patients with CF.
In our specialist cardiothoracic centre, the prevalence of triazole-resistant A. fumigatus is alarmingly high (13.2%). The majority of azole-resistant isolates were from patients with CF. We found a higher prevalence of the environmentally driven mutation TR/L98H in our A. fumigatus isolates than in published UK data from other specialist respiratory centres, which may reflect differing patient populations managed at these institutions.
评估英国伦敦一家专业心胸中心临床分离株中烟曲霉对三唑类药物耐药的流行情况和常见分子 CYP51A 多态性。
2014 年 4 月至 2016 年 3 月,前瞻性分析所有烟曲霉分离株。采用四孔 VIPcheckTM 板筛选分离株以评估三唑类药物敏感性。根据欧洲抗菌药物敏感性试验委员会(EUCAST)指南,采用标准微量肉汤稀释法确认耐药性。对三唑类耐药的烟曲霉分离株进行混合格式实时聚合酶链反应(RT-PCR)检测(AsperGenius),以检测常见 CYP51A 改变。
我们从 135 名患者中鉴定出 167 株临床烟曲霉分离株。18 名患者(13.3%)的 167 株分离株中有 22 株(13.2%)对至少一种唑类抗真菌药物耐药,包括 12 名囊性纤维化(CF)患者(16.2%)。唑类耐药烟曲霉的最高检出率见于 11-20 岁年龄组。所有三唑类耐药分离株(n=22)均对伊曲康唑耐药,18 株对泊沙康唑交叉耐药,10 株对伏立康唑显示敏感性降低。未发现泛唑类耐药烟曲霉。22 株唑类耐药分离株中有 6 株(27.3%)鉴定出 TR/L98H,12 名 CF 患者中有 5 名(42%)可检出。
在我们的专业心胸中心,三唑类耐药烟曲霉的流行率高得惊人(13.2%)。大多数唑类耐药分离株来自 CF 患者。我们发现,与英国其他专业呼吸中心发表的英国数据相比,我们的烟曲霉分离株中环境驱动的突变 TR/L98H 的流行率更高,这可能反映了这些机构管理的不同患者人群。