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过氧化氢对5种唑类药物体外抗耐药白假丝酵母菌的协同作用
张姗姗,王彦,李德东,曹永兵,姜远英*
0
(第二军医大学药学院新药研究中心,上海 200433
共同第一作者
*通信作者)
摘要:
目的 考察过氧化氢(H2O2)对5种唑类药物:氟康唑(FLC),伊曲康唑(ICZ),酮康唑(KCZ),咪康唑(MCZ)和硫康唑(SCZ)体外抗耐药白假丝酵母菌作用的影响。方法 利用8株对氟康唑耐药,2株对氟康唑敏感的白假丝酵母菌,采用微量液基稀释法测定药物单用时的最低抑菌浓度MIC80值,采用棋盘式微量液基稀释法测定两药联用时的MIC80值,在此基础上计算部分抑菌浓度指数(FICI)即协同指数,依据FICI值判断H2O2与唑类药物联用是具有协同、无关还是拮抗作用。结果 对所有耐药菌株,两药联用的FICI值均小于0.5,H2O2与唑类药物联用显现出协同作用;对2株敏感菌株,两药联用的FICI值大于0.5、小于2,显示为无关作用。结论 H2O2和唑类药物(氟康唑,伊曲康唑,酮康唑,咪康唑,硫康唑)联用有协同抗耐药白假丝酵母菌作用。
关键词:  过氧化氢  唑类  抗真菌药  药物协同作用
DOI:10.3724/SP.J.1008.2011.01000
投稿时间:2011-03-31修订日期:2011-07-01
基金项目:
Synergetic antifungal effect of hydrogen peroxide with 5 azoles against drug-resistant Candida albicans
ZHANG Shan-shan,WANG Yan,LI De-dong,CAO Yong-bing,JIANG Yuan-ying*
(Research Center of New Drugs, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
Co-first authors.
*Corresponding author.)
Abstract:
ObjectiveTo investigate the influence of hydrogen peroxide (H2O2) on the antifungal effect of 5 azoles (fluconazole, itraconazole, ketoconazole, miconazole, and sulconazole) against drug-resistant Candida albicans. MethodsEight strains of drug-resistant Candida albicans and two strains of drug-susceptible Candida albicans were used in this study. The minimal inhibitory concentration for 80% (MIC80) of each individual antifungal drug was determined by broth microdilution antifungal susceptibility testing; the MIC80 of the antifungal drug was also determined when in combination with H2O2 by checkerboard microdilution assay. Then the fractional inhibitory concentration index (FICI) was calculated to decide the synergism, indifference, or antagonism of H2O2 with azoles. ResultsThe FICI values of the 8 drug-resistant strains for combination of H2O2 with 5 azoles were less than 0.5, indicating the presence of synergism. The FICI values of the two drug-susceptible strains were between 0.5 and 2, indicating the presence of indifference. ConclusionH2O2 and the azoles (fluconazole, itraconazole, ketoconazole, miconazole and sulconazole) possess synergism effect against drug-resistant Candida albicans.
Key words:  hydrogen peroxide  azoles  antifungal agents  drug synergism