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烟曲霉对医用三唑类药物耐药性可能的环境起源

Possible environmental origin of resistance of Aspergillus fumigatus to medical triazoles.

作者信息

Snelders Eveline, Huis In 't Veld Robert A G, Rijs Anthonius J M M, Kema Gert H J, Melchers Willem J G, Verweij Paul E

机构信息

Department of Medical Microbiology, Radboud University Nijmegen Medical Center, The Netherlands.

出版信息

Appl Environ Microbiol. 2009 Jun;75(12):4053-7. doi: 10.1128/AEM.00231-09. Epub 2009 Apr 17.

Abstract

We reported the emergence of resistance to medical triazoles of Aspergillus fumigatus isolates from patients with invasive aspergillosis. A dominant resistance mechanism was found, and we hypothesized that azole resistance might develop through azole exposure in the environment rather than in azole-treated patients. We investigated if A. fumigatus isolates resistant to medical triazoles are present in our environment by sampling the hospital indoor environment and soil from the outdoor environment. Antifungal susceptibility, resistance mechanisms, and genetic relatedness were compared with those of azole-resistant clinical isolates collected in a previous study. Itraconazole-resistant A. fumigatus (five isolates) was cultured from the indoor hospital environment as well as from soil obtained from flower beds in proximity to the hospital (six isolates) but never from natural soil. Additional samples of commercial compost, leaves, and seeds obtained from a garden center and a plant nursery were also positive (four isolates). Cross-resistance was observed for voriconazole, posaconazole, and the azole fungicides metconazole and tebuconazole. Molecular analysis showed the presence of the dominant resistance mechanism, which was identical to that found in clinical isolates, in 13 of 15 environmental isolates, and it showed that environmental and clinical isolates were genetically clustered apart from nonresistant isolates. Patients with azole-resistant aspergillosis might have been colonized with azole-resistant isolates from the environment.

摘要

我们报告了侵袭性曲霉病患者中烟曲霉分离株对医用三唑类药物产生耐药性的情况。发现了一种主要的耐药机制,我们推测唑类耐药性可能是通过环境中的唑类暴露而非在接受唑类治疗的患者中产生的。我们通过对医院室内环境和室外环境土壤进行采样,调查环境中是否存在对医用三唑类耐药的烟曲霉分离株。将抗真菌药敏性、耐药机制及遗传相关性与先前研究中收集的唑类耐药临床分离株进行比较。从医院室内环境以及医院附近花坛土壤(6株)中培养出了对伊曲康唑耐药的烟曲霉(5株),但天然土壤中未培养出。从园艺中心和植物苗圃获取的商业堆肥、树叶和种子的其他样本也呈阳性(4株)。观察到对伏立康唑、泊沙康唑以及唑类杀菌剂丙环唑和戊唑醇存在交叉耐药性。分子分析显示,15株环境分离株中有13株存在与临床分离株相同的主要耐药机制,且结果表明环境分离株和临床分离株在基因上聚类,与非耐药分离株不同。唑类耐药曲霉病患者可能已被环境中的唑类耐药分离株定植。

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