Laboratoire de Parasitologie-Mycologie, Groupe hospitalier Chenevier-Mondor, Assitance Publique-Hôpitaux de Paris, Créteil, France.
J Antimicrob Chemother. 2011 Feb;66(2):371-4. doi: 10.1093/jac/dkq450. Epub 2010 Dec 5.
An increase in invasive aspergillosis (IA) due to azole-resistant Aspergillus fumigatus isolates has been reported for 10 years. Our study aimed to estimate the prevalence of azole resistance in isolates prospectively collected in patients with haematological diseases.
One hundred and eighteen isolates were collected from 89 consecutive patients over 4 years. Fifty-one patients had proven or probable IA. Species identification was ascertained based on β-tubulin gene sequencing. The MICs of azole drugs were determined using Etest(®), and the cyp51A gene and its promoter were sequenced to detect mutations.
All isolates were identified as A. fumigatus and all of them but one had itraconazole and voriconazole MICs of ≤ 2 mg/L and posaconazole MICs of ≤ 0.25 mg/L. An isolate for which the itraconazole MIC was high (itraconazole MIC = 16 mg/L; voriconazole MIC = 0.38 mg/L; and posaconazole MIC = 0.25 mg/L) was recovered from a patient naive to azole treatment and had a new G432S substitution. To establish whether this mutation existed in other isolates, the 1426-2025 bp cyp51A locus was sequenced for all. G432S was not found.
In A. fumigatus, the prevalence of azole resistance is currently low in the haematological population in the Paris area. Surveillance programmes for azole resistance to adapt antifungal treatments are warranted for clinical isolates of A. fumigatus.
已有报道称，10 年来，由于唑类药物耐药的烟曲霉分离株，侵袭性曲霉病（IA）的发病率有所增加。本研究旨在评估前瞻性采集血液病患者分离株中唑类耐药的发生率。
在 4 年期间，从 89 例连续患者中收集了 118 株分离株。51 例患者患有确诊或疑似侵袭性曲霉病。根据β-微管蛋白基因测序确定物种鉴定。使用 Etest（®）测定唑类药物的 MIC，测序 cyp51A 基因及其启动子以检测突变。
所有分离株均被鉴定为烟曲霉，除一株外，所有分离株的伊曲康唑和伏立康唑 MIC 均≤2mg/L，泊沙康唑 MIC 均≤0.25mg/L。一株伊曲康唑 MIC 较高（伊曲康唑 MIC=16mg/L；伏立康唑 MIC=0.38mg/L；泊沙康唑 MIC=0.25mg/L）的分离株来自未接受唑类药物治疗的患者，且存在新的 G432S 取代。为了确定该突变是否存在于其他分离株中，对所有分离株的 1426-2025bp cyp51A 基因座进行了测序。未发现 G432S。
在烟曲霉中，目前巴黎地区血液病患者中唑类耐药的流行率较低。需要对临床分离株进行唑类耐药监测计划，以调整抗真菌治疗。
