Emergence of Azole Resistance in Aspergillus

被引:38
|
作者
Wiederhold, Nathan P. [1 ,2 ]
Patterson, Thomas F. [2 ,3 ]
机构
[1] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78229 USA
[2] UTHSCSA, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA
[3] South Texas Vet Hlth Care Syst, San Antonio, TX USA
关键词
Aspergillus fumigatus; azole resistance; aspergillosis; voriconazole; itraconazole; posaconazole; CYP51A; INVASIVE PULMONARY ASPERGILLOSIS; AMPHOTERICIN-B; NEOSARTORYA-PSEUDOFISCHERI; ITRACONAZOLE RESISTANCE; ISAVUCONAZOLE BAL4815; ANTIFUNGAL RESISTANCE; FUMIGATUS; VORICONAZOLE; POSACONAZOLE; MECHANISMS;
D O I
10.1055/s-0035-1562894
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Resistance to the azole antifungals itraconazole, voriconazole, and posaconazole in Aspergillus species is a growing concern. This is especially alarming for A. fumigatus, where acquired resistance has been documented in patients with invasive disease caused by this species that were exposed to these agents, as well as in azole-naive individuals. The primary mechanisms of resistance that have been described in clinical strains include different point mutations in the CYP51A gene, which encodes the enzyme responsible for converting lanosterol to ergosterol via demethylation. Some resistant isolates also contain a tandem repeat in the promoter region of this gene that causes increased expression. These mutations, including TR34/L98H and TR46/Y121F/T289A have also been found in the environment in several areas of the world and have been demonstrated to cause resistance to azole fungicides used in agriculture, thus raising the concern of environmental spread of resistance. Treatment options are limited in patients with infections caused by azole-resistant isolates and include amphotericin B formulations or combination therapy involving an echinocandin. However, there are few clinical data available to help guide therapy, and infections caused by resistant A. fumigatus isolates have been reported to have high mortality rates.
引用
收藏
页码:673 / 680
页数:8
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