国产两性霉素B及其他常用抗真菌药物对侵袭性真菌病病原菌的体外抑菌活性研究

中国真菌学杂志　 2018, Vol. 13 　Issue (5): 277-282.

国产两性霉素B及其他常用抗真菌药物对侵袭性真菌病病原菌的体外抑菌活性研究

周亚彬, 王千, 张浩, 万喆, 李若瑜, 刘伟

北京大学第一医院皮肤性病科北京大学真菌与真菌病研究中心皮肤病分子诊断北京市重点实验室, 北京 100034

收稿日期:2018-03-30 出版日期:2018-10-28 发布日期:2018-10-28
通讯作者: 刘伟,E-mail:liuwei@bjmu.edu.cn E-mail:liuwei@bjmu.edu.cn
作者简介:周亚彬,男(汉族),博士研究生在读.E-mail:chouyabin@163.com
基金资助:
国家自然科学基金（81471925，81671990）

In vitro antifungal activity of domestic amphotericin B and other common antifungal agents against pathogenic fungi isolated from invasive fungal disease

ZHOU Ya-bin, WANG Qian, ANG Hao, WAN Zhe, LI Ruo-yu, Liu Wei

Department of Dermatology & Venereology, Peking University First Hospital, Research Center for Medical Mycology, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Peking University, Beijing 100034

Received:2018-03-30 Online:2018-10-28 Published:2018-10-28

摘要/Abstract

摘要：

目的了解国产两性霉素B（AMB）及其他常用抗真菌药物对侵袭性真菌病病原菌的体外抑菌活性。方法参照美国临床和实验室标准协会（CLSI）制定的M27-A3和M38-A2方案测定国产AMB及其他常用抗真菌药物对108株侵袭性真菌病致病菌的最低抑菌浓度（MIC）或最低有效浓度（MEC）值。结果 AMB对受测几乎所有菌株的MIC值均≤ 2 mg/L，但对土曲霉、多育赛多孢、尖端赛多孢的MIC值分别为2~4 mg/L、>16 mg/L、1~8 mg/L；AMB对耐唑类药物的念珠菌及曲霉的MIC值均2 mg/L；氟康唑（FLC）对受测的所有丝状真菌的MIC值均>64 mg/L；伊曲康唑（ITR）对茄病镰刀菌、多育赛多孢、卷枝毛霉等的MIC值分别为8 mg/L、>16 mg/L、>16 mg/L；伏立康唑（VRC）对茄病镰刀菌、多育赛多孢及受测的所有毛霉的MIC值均≥ 16 mg/L；泊沙康唑（POS）对茄病镰刀菌、多育赛多孢、卷枝毛霉等的MIC值均>16 mg/L；米卡芬净（MCF）和卡泊芬净（CAS）对隐球菌、毛孢子菌、毛霉、茄病镰刀菌及尖端赛多孢菌的MIC及MEC值均≥ 16 mg/L，对多育赛多孢菌的MEC值分别为8 mg/L和4 mg/L。结论同其他常用抗真菌药相比，AMB对分离自中国的常见侵袭性真菌病的病原菌有良好的体外抗菌活性，但对土曲霉和赛多孢菌抑菌活性较弱。

关键词: 抗真菌药物, 两性霉素B, 体外敏感性试验, 病原真菌

Abstract:

Objective To investigate the in vitro antifungal activity of domestic amphotericin B and other common antifungal agents against the clinical isolates associated with invasive fungal disease. Methods Minimal inhibitory concentration (MIC) or minimum effect concentration (MEC) of domestic amphotericin B and other common antifungal agents against 108 strains associated with invasive fungal disease were tested by using CLSI (Clinical and Laboratory Standards Institute) broth microdilution method M27-A3 and M38-A2. Results The MICs of amphotericin B against almost all strains tested were less than or equal to 2 mg/L, except Aspergillus terreus, Scedosporium prolificans and S. apiospermum (MIC range of 2-4 mg/L, >16 mg/L, 1-8 mg/L, respectively). The MICs of amphotericin B against azole-resistant Candida and Aspergillus were less than or equal to 2 mg/L. The MICs of fluconazole against all the filamentous fungi tested were greater than 64 mg/L. The MICs of itraconazole against Fusarium solani, S. prolificans and Mucor circinelloides were 8 mg/L, >16 mg/L, >16 mg/L, respectively. The MICs of voriconazole against F. solani, S. prolificans and all Mucor tested were greater than 16 mg/L. The MICs of posaconazole against Fusarium solani, S. prolificans and Mucor circinelloides were all greater than 16 mg/L. The MICs/MECs of caspofungin and micafungin against Cryptococcus, Trichosporon, Mucor, F. solani and Scedosporium were all greater than 16 mg/L. The MECs of caspofungin and micafungin against S. prolificans were 8 and 4 mg/L, respectively. Conclusion Compared with other common antifungal agents, amphotericin B is active against the clinical isolates associated with invasive fungal disease, except A. terreus and Scedosporium.

Key words: antifungal agent, amphotericin B, in vitro susceptibility tests, pathogenic fungi

中图分类号:

R978.5

周亚彬, 王千, 张浩, 万喆, 李若瑜, 刘伟. 国产两性霉素B及其他常用抗真菌药物对侵袭性真菌病病原菌的体外抑菌活性研究[J]. 中国真菌学杂志, 2018, 13(5): 277-282.

ZHOU Ya-bin, WANG Qian, ANG Hao, WAN Zhe, LI Ruo-yu, Liu Wei. In vitro antifungal activity of domestic amphotericin B and other common antifungal agents against pathogenic fungi isolated from invasive fungal disease[J]. Chinese Journal of Mycology, 2018, 13(5): 277-282.

参考文献

[1] Enoch DA, Yang H, Aliyu SH, et al. The Changing Epidemiology of Invasive Fungal Infections[J]. Methods Mol Biol, 2017, 1508(Suppl 1):17-65.
[2] Barnes PD, Marr KA. Risks, diagnosis and outcomes of invasive fungal infections in haematopoietic stem cell transplant recipients[J]. Br J Haematol, 2007, 139(4):519-531.
[3] Hamill RJ. Amphotericin B formulations:a comparative review of efficacy and toxicity[J]. Drugs, 2013, 73(9):919-934.
[4] Clinical and Laboratory Standards Institute.Reference method for broth dilution antifungal susceptibility testing of yeasts; Approved Standard-Third Edition.CLSI document M27-A3[S].Wayne,PA:Clinical and Laboratory Standards Institute, 2008.
[5] Clinical and Laboratory Standards Institute.Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; Approved Standard-Second Edition.CLSI document M38-A2[S].Wayne,PA:Clinical and Laboratory Standards Institute, 2008.
[6] Cao C, Liu W, Li R, et al. In vitro interactions of micafungin with amphotericin B, itraconazole or fluconazole against the pathogenic phase of Penicillium marneffei[J]. J Antimicrob Chemother, 2009, 63(2):340-342.
[7] 李强国, 李昕, 曹存巍. 两种钙调磷酸酶抑制剂联合常用抗真菌药物对马尔尼菲青霉酵母相体外药敏的研究[J]. 广西医科大学学报, 2015, 32(2):169-172.
[8] Clinical and Laboratory Standards Institute.Reference method for broth dilution antifungal susceptibility testing of yeasts; Fourth Information Supplement. CLSI document M27-S4[S].Wayne,PA:Clinical and Laboratory Standards Institute, 2012.
[9] Pastor FJ, Guarro J. Treatment of Aspergillus terreus infections:a clinical problem not yet resolved[J]. Int J Antimicrob Agents, 2014, 44(4):281-289.
[10] Fera MT, La CE, De SA. New triazoles and echinocandins:mode of action, in vitro activity and mechanisms of resistance[J]. Expert Rev Anti Infect Ther, 2009, 7(8):981.
[11] Montoya AM, Sánchez González A, Palma-Nicolás JP, et al. Genotyping, extracellular compounds, and antifungal susceptibility testing of Trichosporon asahii isolated from Mexican patients[J]. Med Mycol, 2015, 53(5):505-511.
[12] Tomazin R, Matos T, Meis JF, et al. Molecular characterization and antifungal susceptibility testing of sequentially obtained clinical Cryptococcus deneoformans and Cryptococcus neoformans isolates from Ljubljana, Slovenia[J]. Mycopathologia, 2018, 183(6):371-380.
[13] Gupta C, Jongman M, Das S, et al. Genotyping and in vitro antifungal susceptibility testing of Fusarium isolates from onychomycosis in India[J]. Mycopathologia, 2016, 181(7-8):497-504.
[14] Homa M, Galgóczy L, Tóth E, et al. In vitro antifungal activity of antipsychotic drugs and their combinations with conventional antifungals against Scedosporium and Pseudallescheria isolates[J]. Med Mycol, 2015, 53(8):890-895.
[15] 王澎, 徐英春, 窦洪涛,等. 尖端赛多孢和多育赛多孢所致的深部真菌感染2例并文献复习[J]. 中国真菌学杂志, 2007, 2(4):210-213.
[16] Drogari-Apiranthitou M, Mantopoulou FD, Skiada A, et al. In vitro antifungal susceptibility of filamentous fungi causing rare infections:synergy testing of amphotericin B, posaconazole and anidulafungin in pairs[J]. J Antimicrob Chemother, 2012, 67(8):1937-1940.
[17] Vitale RG, de Hoog GS, Schwarz P, et al. Antifungal susceptibility and phylogeny of opportunistic members of the order mucorales[J]. J Clin Microbiol, 2012, 50(1):66-75.
[18] Chowdhary A, Kathuria S, Singh PK, et al. Molecular characterization and in vitro antifungal susceptibility of 80 clinical isolates of mucormycetes in Delhi, India[J]. Mycoses, 2015, 57(s3):97-107.