深部真菌感染的耐药机制研究进展_West China Medical Journal

Authors：

代华 , 陈木英 , 陈立宇 ,  王晓辉

Corresponding author：

王晓辉, Email: auhiad0208@126.com

Keywords：

真菌; 耐药机制; 真菌外排泵; 靶酶CYP51; FKS1基因

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【摘要】 随着深部真菌感染日益增加及抗真菌药物的广泛应用，深部真菌耐药现象也日益突出。近十年以来，虽有较多新型抗真菌感染药物相继研发并应用于临床，但国内外已有较多对其耐药的病案报道。真菌面对唑类等强大的抗真菌药物也不断产生着严重的耐药性，并迅速使一些院内真菌感染陷入了无药可选的境地。因此，研究真菌的耐药机制并寻找新的抗真菌药物已成当务之急。现就按照抗真菌药物分类，对近年来国内外深部真菌感染的耐药机制的研究进展进行综述，以明确深部真菌耐药发生的诱因、机制，为指导临床合理使用抗真菌药物；尽可能减少深部真菌耐药的发生及研究新一代抗真菌药物提供参考。

Citation： 代华,陈木英,陈立宇,王晓辉. 深部真菌感染的耐药机制研究进展. West China Medical Journal, 2011, 26(1): 142-145. doi: Copy

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26.	Balashov SV, Park S, Perlin DS. Assessing resistance to the echinocandin antifungal drug caspofungin in Candida albicans by profiling mutations in FKS1[J]. Antimicrob Agents Chemother, 2006, 50(6): 2058-2063.
27.	Park S, Kelly R, Kahn JN, et al. Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates[J]. Antimicrob Agents Chemother, 2005, 49(8): 3264-3273.

1. 　周巧霞, 张经硕. 抗真菌药物及其临床应用进展[J]. 抗感染药物, 2008, 5(1): 11-18.
2. 　Kanafani ZA, Perfect JR. Antimicrobial resistance: resistance to antifungal agents: mechanisms and clinical impact[J]. Clin Infect Dis, 2008, 46 (1): 120-128.
3. 　周露, 斯拉普, 艾白. 抗深部真菌感染药物的研究进展[J]. 药学进展, 2010, 7(7): 898-900.
4. 　Macbashi K, Niimi M, Kudoh M, et al. Mechanisms of fluconazole resistance in Candida albicans isolates from Japanese AIDS patients[J]. Antimicrob Chemother, 2001, 47(5): 527.
5. 　Marr KA, Lyons CN, Ha K, et al. Inducible azole resistance associated with a heterogeneous phenotype in Candida albicans[J]. Anti Agents Chemo, 2001, 45(1): 52.
6. 　Micheli M, Bille J, Schueller C, et al. A common drug-responsive element mediates the upregulation of the Candida albicans ABC transporters CDR1 and CDR2, two genes involved in antifungal drugresistance[J]. Mol Microbiol, 2002, 43(5): 1197-1214.
7. 　Mar MC, Felix GR. Antifungal drug resistance to azole and polyenes[J]. Lancet Infect Dis, 2002, 9(2): 550-563.
8. 　Edlind TD, Henry KW, Metera KA, et al. Aspergillus fumigatus CYP51 sequence: potential basis for fluconazole resistance[J]. Med Mycol, 2001, 39(3): 299.
9. 　Kontoyiannis DP, Lewis RE. Antifungal drug resistance of pathogenic fungi[J]. Lancet, 2002, 359 (9312): 1135-1144.
10. 　乔建军, 刘伟, 李若瑜. 白色念珠菌耐药的分子研究机制研究进展[J]. 微生物学通报, 2007, 34(2): 393-396.
11. 　Kohli A, Smriti, Mukhopadhyay K, et al. In vitro low-level resistance to azole in Candida albicans is associated with changes in membrane lipid fluidity and asymmetry[J]. Anti Agents Chemo, 2002, 46(4): 1046.
12. 　Emter R, Heese-Peck A, Kralli A. ERG6 and PDR5 regulate small lipophilic drug accumulation in yeast cells via distinct mechanisms[J]. FEBS Lett, 2009, 521(1-3): 57-61.
13. 　Espinel-Ingroff A. Mechanisms of resistance to antifungalag-ents: Yeasts and filamentous fungi[J]. Rev Iberoam Micol, 2008, 25(2): 101-106.
14. 　于维林, 朱元祺, 刘蓬蓬, 等. 唑类耐药白色念珠菌羊毛甾醇14α-去甲基化酶基因的研究[J]. 中国实验诊断学, 2009, 10(13): 1357-1359.
15. 　綦颖, 夏国光. 侵袭性真菌感染的流行病学和抗真菌药物的作用效力[J]. 中华医院感染学杂志, 2009, 19(16): 2217-2220.
16. 　Rock FL, Mao W, Anya YA, et al. An antifungal agentinhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site[J]. Science, 2007, 316(5832): 1759-1761.
17. 　胡辉, 白色念珠菌生物被膜形成和由其产生的耐药机制[J]. 国外医药•抗生素分册, 2008, 29(1): 1-6.
18. 　Hope WW, Tabemero L, Denning DW, et al. Molecular mechanisms of primary resistance to flucytosine in Candida albicans[J]. Anti Agents Chemo, 2004, 48: 4377-4386.
19. 　李婷婷, 朱若华, 蔡光明, 等. 抗真菌药物的研究进展[J]. 中国药房, 2010, 21(16): 1533-1536.
20. 　Akings RA. An update on antifungal targets and mechanisms of resistance in Candida albicans[J]. Med Mycol, 2005, 43(4): 285-318.
21. 　田伟, 王育英. 特比奈芬治疗浅部真菌病的临床应用[J]. 临床皮肤科杂志, 2008, 09(51): 622-623.
22. 　陈螟, 曹国颖, 傅得兴, 等. 棘白菌素类抗真菌药物的研究进展[J]. 中国新药杂志, 2007, 16(14): 1082-1083.
23. 　叶丽娟, 王辂, 朱辉. 抗真菌药物的作用机制及真菌耐药机制的研究进展[J]. 中国新药杂志, 2007, 16(14): 1082-1083.
24. 　Katiyar S, Pfaller M, Edlind T. Candida albicans and Candida glabrata clinical isolates exhibiting reduced echinocandin susceptibility[J]. Antimicrob Agents Chemother, 2006, 50(8): 2892-2894.
25. 　Gardiner RE, Souteropoulos P, Park S, et al. Characterization of Aspergillus fumigatus mutants with reduced suscepti-bility to caspofungin[J]. Med Mycol, 2005, 43(l1): 299-305.
26. 　Balashov SV, Park S, Perlin DS. Assessing resistance to the echinocandin antifungal drug caspofungin in Candida albicans by profiling mutations in FKS1[J]. Antimicrob Agents Chemother, 2006, 50(6): 2058-2063.
27. 　Park S, Kelly R, Kahn JN, et al. Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates[J]. Antimicrob Agents Chemother, 2005, 49(8): 3264-3273.

West China Medical Journal

深部真菌感染的耐药机制研究进展

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