Mycology Unit, Department of Microbiological Surveillance and Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
J Clin Microbiol. 2011 Jun;49(6):2243-51. doi: 10.1128/JCM.00213-11. Epub 2011 Apr 20.
Respiratory tract colonization by molds in patients with cystic fibrosis (CF) were analyzed, with particular focus on the frequency, genotype, and underlying mechanism of azole resistance among Aspergillus fumigatus isolates. Clinical and demographic data were also analyzed. A total of 3,336 respiratory samples from 287 CF patients were collected during two 6-month periods in 2007 and 2009. Azole resistance was detected using an itraconazole screening agar (4 mg/liter) and the EUCAST method. cyp51A gene sequencing and microsatellite genotyping were performed for isolates from patients harboring azole-resistant A. fumigatus. Aspergillus spp. were present in 145 patients (51%), of whom 63 (22%) were persistently colonized. Twelve patients (4%) harbored other molds. Persistently colonized patients were older, provided more samples, and more often had a chronic bacterial infection. Six of 133 patients (4.5%) harbored azole-nonsusceptible or -resistant A. fumigatus isolates, and five of those six patients had isolates with Cyp51A alterations (M220K, tandem repeat [TR]/L98H, TR/L98H-S297T-F495I, M220I-V101F, and Y431C). All six patients were previously exposed to azoles. Genotyping revealed (i) microevolution for A. fumigatus isolates received consecutively over the 2-year period, (ii) susceptible and resistant isolates (not involving TR/L98H isolates) with identical or very closely related genotypes (two patients), and (iii) two related susceptible isolates and a third unrelated resistant isolate with a unique genotype and the TR/L98H resistance combination (one patient). Aspergilli were frequently found in Danish CF patients, with 4.5% of the A. fumigatus isolates being azole nonsusceptible or resistant. Genotyping suggested selection of resistance in the patient as well as resistance being achieved in the environment.
对囊性纤维化 (CF) 患者的呼吸道霉菌定植进行了分析，特别关注烟曲霉分离株中唑类药物耐药的频率、基因型和潜在机制。还分析了临床和人口统计学数据。在 2007 年和 2009 年的两个 6 个月期间，共从 287 名 CF 患者中采集了 3336 份呼吸道样本。使用伊曲康唑筛选琼脂 (4mg/L) 和 EUCAST 方法检测唑类药物耐药性。对携带唑类药物耐药烟曲霉的患者的分离株进行 cyp51A 基因测序和微卫星基因分型。在 145 名患者（51%）中存在曲霉菌属，其中 63 名（22%）持续定植。12 名患者（4%）定植其他霉菌。持续定植的患者年龄较大，提供的样本较多，且经常患有慢性细菌感染。在 133 名患者中，有 6 名（4.5%）定植的烟曲霉对唑类药物不敏感或耐药，其中 5 名患者的分离株存在 Cyp51A 改变（M220K、串联重复[TR]/L98H、TR/L98H-S297T-F495I、M220I-V101F 和 Y431C）。所有 6 名患者均有唑类药物暴露史。基因分型显示：（i）在 2 年期间连续分离的烟曲霉分离株发生微进化；（ii）具有相同或非常相似基因型的敏感和耐药分离株（不涉及 TR/L98H 分离株）（2 名患者）；（iii）2 个相关敏感分离株和第 3 个无关耐药分离株，具有独特基因型和 TR/L98H 耐药组合（1 名患者）。丹麦 CF 患者中经常发现曲霉菌，其中 4.5%的烟曲霉分离株对唑类药物不敏感或耐药。基因分型表明耐药性是在患者体内选择的，也是在环境中获得的。
