Verweij Paul E, Snelders Eveline, Kema Gert H J, Mellado Emilia, Melchers Willem J G
Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
Lancet Infect Dis. 2009 Dec;9(12):789-95. doi: 10.1016/S1473-3099(09)70265-8.
Invasive aspergillosis due to multi-azole-resistant Aspergillus fumigatus has emerged in the Netherlands since 1999, with 6.0-12.8% of patients harbouring resistant isolates. The presence of a single resistance mechanism (denoted by TR/L98H), which consists of a substitution at codon 98 of cyp51A and a 34-bp tandem repeat in the gene-promoter region, was found in over 90% of clinical A fumigatus isolates. This is consistent with a route of resistance development through exposure to azole compounds in the environment. Indeed, TR/L98H A fumigatus isolates were cultured from soil and compost, were shown to be cross-resistant to azole fungicides, and genetically related to clinical resistant isolates. Azoles are abundantly used in the environment and the presence of A fumigatus resistant to medical triazoles is a major challenge because of the possibility of worldwide spread of resistant isolates. Reports of TR/L98H in other European countries indicate that resistance might already be spreading.
自1999年以来，荷兰出现了由多重唑类耐药烟曲霉引起的侵袭性曲霉病，6.0%至12.8%的患者携带耐药菌株。在超过90%的临床烟曲霉分离株中发现了单一耐药机制（由TR/L98H表示），该机制由cyp51A基因第98位密码子的替换和基因启动子区域的34 bp串联重复组成。这与通过环境中接触唑类化合物产生耐药性的途径一致。事实上，从土壤和堆肥中培养出了TR/L98H烟曲霉分离株，这些分离株对唑类杀菌剂具有交叉耐药性，并且在基因上与临床耐药分离株相关。唑类在环境中被大量使用，耐医用三唑类的烟曲霉的存在是一个重大挑战，因为耐药菌株有可能在全球范围内传播。其他欧洲国家关于TR/L98H的报告表明耐药性可能已经在传播。
