Chamilos G, Kontoyiannis D P
Department of Infectious Diseases, Infection Control and Employee Health, Unit 402, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Drug Resist Updat. 2005 Dec;8(6):344-58. doi: 10.1016/j.drup.2006.01.001. Epub 2006 Feb 20.
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 study 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.
尽管在过去十年中，具有抗曲霉活性的药物种类有所增加，但侵袭性曲霉病（IA）导致的死亡率仍然高得令人难以接受。烟曲霉仍然是IA的主要致病菌；然而，对抗真菌药物不太敏感的非烟曲霉开始出现。曲霉的抗真菌药物耐药性可能是治疗失败的部分原因。我们对曲霉抗真菌药物作用机制的理解取得了新进展，同时体外药敏试验方法也实现了标准化，这使得耐药性检测成为临床真菌学的前沿问题。此外，分子生物学已开始揭示烟曲霉对唑类和棘白菌素类药物的耐药机制，而基于基因组的检测方法有望用于高通量筛选基因型抗真菌耐药性。然而，在这个复杂领域的研究中仍存在一些问题。缺乏大型多中心临床研究（现患率或纵向研究）来了解烟曲霉分离株中抗真菌耐药性的发生率和流行情况。体外药敏试验与临床结果及药敏折点之间的相关性尚未确立。此外，新型三唑类药物之间的交叉耐药问题也备受关注。此外，两性霉素B和棘白菌素类药物的体外耐药性检测困难，其耐药机制也大多未知。本综述探讨了烟曲霉在抗真菌药物耐药性的诊断、流行病学及机制方面所面临的挑战。
