氟康唑协同土槿皮甲酸抗白念珠菌活性研究  

Study on antimicrobial activity of fluconazole combined with pseudolaric acid A against Candida albicans

作　　者：诸斌 李贞 陈伟琴[1] 殷红梅[1] 胡晓波[1] Zhu Bin;Li Zhen;Chen Wei-qin;Yin Hong-mei;Hu Xiao-bo(Department of Clinical Laboratory,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032)

机构地区：[1]上海中医药大学附属龙华医院检验科,上海200032

出　　处：《中国抗生素杂志》2021年第12期1127-1132,共6页Chinese Journal of Antibiotics

基　　金：国家自然青年科学基金(No.82003817)。

摘　　要：目的研究体外土槿皮甲酸(PAA)与氟康唑(FLC)联合应用对白念珠菌的抗菌活性。方法采用微量稀释法和棋盘微量稀释法测定PAA与FLC单独应用及联合应用于对临床分离的22株白念珠菌的最低抑菌浓度(MIC),并以部分抑菌浓度指数(FICI)判断两药联合抑菌效应,以CAR3和CA10为目标菌株,采用时间-杀菌曲线动态监测两药体外抑菌效果。结果PAA单独作用于白念珠菌时,无论是对FLC耐药菌株还是对FLC敏感菌株,均呈现较好的抑菌效果,其中位MIC范围为4~16μg/mL。当PAA与FLC联用对抗耐药白念珠菌时,可将FLC的单用浓度范围从256~512μg/mL降至为1~2μg/mL。根据FICI测定,11株对FLC耐药菌株FICI介于0.039~0.253之间,均表现出协同抑菌作用;而11株对FLC敏感菌株,仅有2株(18.2%)FICI范围为0.312~0.375,呈现出协同抑菌作用,剩余9株(81.8%)FICI介于0.625~1.125之间,两种药物呈现出无关作用。时间-杀菌曲线也证实,与氟康唑单用相比,PAA与FLC联用24h后,CAR3、CA10菌株的lgCFU/mL分别下降了2.22个单位和1.57个单位,耐药菌株表现出协同作用,而敏感菌株表现出无关作用。结论PAA对白念珠菌表现出较好的抑菌效力,与低浓度FLC联用对耐药白念珠菌具有体外协同抑菌作用,能显著提高FLC对耐药白念珠菌的抗菌活性。Objective To study the antimicrobial activity of pseudolaric acid A(PAA)and fluconazole(FLC)against Candida albicans in vitro.Methods The minimum inhibitory concentrations(MIC)of PAA alone and in combination with FLC against 22 strains of Candida albicans isolated clinically were determined by the microdilution method and the chessboard microdilution method.The bacteriostatic effect of the combination of the two drugs was evaluated by the fractional inhibitory concentration index(FICI).Taking CAR3 and CA10 as target strains,the timekilling curve was used to dynamically monitor the bacteriostatic effect of the two drugs in vitro.Results When PAA acted on Candida albicans alone,it had good bacteriostatic effect on both FLC-resistant and FLC-sensitive strains.The median MIC was in the range of 4~16μg/mL.When PAA was combined with FLC against drug-resistant Candida albicans,the concentration range of FLC could be reduced from 256~512μg/mL to 1~2μg/mL.According to the determination of FICI,the FICI of 11 FLC-resistant strains ranged from 0.039 to 0.253,all of which showed synergistic bacteriostatic effect.Of the 11 FLC-sensitive strains,only 2(18.2%)showed synergistic bacteriostatic effect in the FICI range of 0.312 to 0.375,while the remaining 9(81.8%)showed irrelevant effects in the FICI range of 0.625 to 1.125.The time-killing curve also confirmed that compared with fluconazole alone,the lgCFU/mL of CAR3 and CA10 strains decreased by 2.22U and 1.57U respectively after PAA combined with FLC for 24h.The drug-resistant strains showed synergistic effect,while the drug-sensitive strains showed irrelevant effects.Conclusion PAA shows good bacteriostatic effect against Candida albicans.PAA combined with low concentration FLC has synergistic bacteriostatic effect on drug-resistant Candida albicans in vitro,which can significantly improve the antimicrobial activity of FLC against drug-resistant Candida albicans.

关 键 词：白念珠菌 土槿皮甲酸 氟康唑 抑菌效果 

分 类 号：R978[医药卫生—药品]