Institute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne, Cologne, Germany.
CF Center, University Children's Hospital of Cologne, Cologne, Germany.
J Antimicrob Chemother. 2014 Jun;69(6):1533-6. doi: 10.1093/jac/dku009. Epub 2014 Jan 31.
Aspergillus spp. are the most frequently isolated filamentous fungi in the sputum of patients with cystic fibrosis (CF). Resistance to the azoles, the mainstay of current antifungal therapy, has been increasingly observed worldwide, but few data are available on the resistance of Aspergillus spp. in German CF patients. This study investigated the epidemiology of Aspergillus spp. and the molecular origin of azole resistance in a large German CF centre.
In total, 2677 respiratory samples from 221 CF patients collected between April 2010 and April 2013 were analysed; of these, 573 yielded Aspergillus spp., which were screened for azole resistance. Isolates with reduced susceptibility to itraconazole and/or voriconazole were tested according to the EUCAST reference procedure. Sequencing of cyp51A, the target of azole antifungals, was performed in all resistant isolates.
Six isolates obtained from four patients were highly resistant to itraconazole (all identified as Aspergillus fumigatus sensu stricto); five of them were pan-azole resistant. The TR34/L98H mutation was the most frequent mutation identified in azole-resistant isolates (n = 4), followed by M220L and TR46/Y121F/T289A, a mutation previously reported from Belgium and the Netherlands only. Three of four patients harbouring azole-resistant A. fumigatus had not received any prior azole treatment.
Resistance to azoles in Aspergillus spp. is still infrequent in German CF patients and is mainly caused by the TR34/L98H mutation. Worryingly, pan-azole-resistant TR46/Y121F/T289A has spread to Germany. Azole resistance has to be considered also in azole-naive CF patients and susceptibility testing of Aspergillus spp. isolates should be performed in all patients requiring treatment.
曲霉菌属是囊性纤维化（CF）患者痰液中最常分离的丝状真菌。抗真菌药物唑类药物的耐药性在全球范围内日益受到关注，但有关德国 CF 患者曲霉菌属耐药性的数据很少。本研究调查了德国大型 CF 中心曲霉菌属的流行情况和唑类耐药的分子起源。
共分析了 2010 年 4 月至 2013 年 4 月期间收集的 221 例 CF 患者的 2677 份呼吸道样本，其中 573 份样本分离出曲霉菌属，对其进行了唑类药物耐药性筛查。对伊曲康唑和/或伏立康唑敏感性降低的分离株按照 EUCAST 参考程序进行检测。对所有耐药分离株进行唑类药物靶标 cyp51A 的测序。
从 4 名患者中获得的 6 株分离株对伊曲康唑高度耐药（均鉴定为烟曲霉）；其中 5 株为泛唑类耐药。在唑类耐药分离株中最常见的突变是 TR34/L98H（n=4），其次是 M220L 和 TR46/Y121F/T289A，这一突变之前仅在比利时和荷兰报道过。携带唑类耐药烟曲霉的 4 名患者中有 3 名未接受过任何唑类药物治疗。
在德国 CF 患者中，曲霉菌属对唑类药物的耐药性仍然罕见，主要由 TR34/L98H 突变引起。令人担忧的是，泛唑类耐药 TR46/Y121F/T289A 已传播到德国。在未接受唑类药物治疗的 CF 患者中也应考虑唑类耐药性，所有需要治疗的患者均应进行曲霉菌属分离株的药敏试验。
