Update on antifungal drug resistance mechanisms of Aspergillus fumigatus

被引:98
作者
Chamilos, G [1 ]
Kontoyiannis, DP [1 ]
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Infect Dis Infect Control & Employee Hlth, Unit 402, Houston, TX 77030 USA
关键词
Aspergillus fumigatus; drug resistance; susceptibility testing; triazoles; amphotericin B;
D O I
10.1016/j.drup.2006.01.001
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Although the arsenal of agents with anti-Aspergillus activity has expanded over the last decade, mortality due to invasive aspergillosis (IA) remains unacceptably high. Aspergillus fumigatus still accounts for the majority of cases of IA; however less susceptible to antifungals non-fumigatus aspergilli began to emerge. Antifungal drug resistance of Aspergillus might partially account for treatment failures. Recent advances in our understanding of mechanisms of antifungal drug action in Aspergillus, along with the standardization of in vitro susceptibility testing methods, has brought resistance testing to the forefront of clinical mycology. In addition, molecular biology has started to shed light on the mechanisms of resistance of A. fumigatus to azoles and the echinocandins, while genome-based assays show promise for high-throughput screening for genotypic antifungal resistance. Several problems remain, however, in the stud), of this complex area. Large multicenter clinical studies - point prevalence or longitudinal - to capture the incidence and prevalence of antifungal resistance in A. fumigatus isolates are lacking. Correlation of in vitro susceptibility with clinical outcome and susceptibility breakpoints has not been established. In addition, the issue of cross-resistance between the newer triazoles is of concern. Furthermore, in vitro resistance testing for polyenes and echinocandins is difficult, and their mechanisms of resistance are largely unknown. This review examines challenges in the diagnosis, epidemiology, and mechanisms of antifungal drug resistance in A. fumigatus. (C) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:344 / 358
页数:15
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