四种中药单体联合亚胺培南对耐碳青霉烯肺炎克雷伯菌体外抑菌作用研究  

Antibacterial Activity of Four Traditional Chinese Medicine Momonomers Combined with Imipenem Against Carbapenem-resistant Klebsiella Pneumoniae in Vitro

作　　者：唐金蓉 张碟 李盛 TANG Jin-rong;ZHANG Die;LI Sheng(Department of Clinical Laboratory,Mianyang Hospital Affililiated to Chengdu University of Traditional Chinese Medicine,Sichuan Mianyang 621000,China)

机构地区：[1]成都中医药大学附属绵阳医院检验科,四川绵阳621000

出　　处：《现代检验医学杂志》2022年第6期162-165,197,共5页Journal of Modern Laboratory Medicine

基　　金：绵阳市卫健委补助项目(202110);四川中医药文化传承与研究中心规划项目(2020Y003)。

摘　　要：目的研究小檗碱、穿心莲内酯、黄芩苷和栀子苷四种中药单体分别联合亚胺培南(imipenem,IMP)对耐碳青霉烯肺炎克雷伯菌(carbapenem-resistant Klebsiella pneumoniae,CRKP)的体外抑菌作用。方法选取成都中医药大学附属绵阳医院2021年1~6月从临床标本中分离出的6株非重复CRKP菌株,微量肉汤稀释法测定四种中药单体分别对6株CRKP的最低抑菌浓度(minimum inhibitory concentration,MIC),棋盘法测定中药单体分别联合IMP对CRKP的MIC,计算部分抑菌浓度指数(FIC)。采用两独立样本的Wilcoxon秩和检验比较各组药物联合前后MIC的变化。结果小檗碱、穿心莲内酯、黄芩苷和栀子苷对CRKP的MIC分别为2500μg/ml,2500μg/ml,5000~10000μg/ml和>10000μg/ml。黄芩苷联合IMP对6株CRKP的FIC为0.375~0.75,出现协同作用(3株),小檗碱、穿心莲内酯和栀子苷联合IMP对CRKP的FIC为0.625~1.25,未出现协同作用。黄芩苷联合IMP后可降低IMP的MIC,差异有统计学意义(Z=-2.459,P<0.05)。小檗碱、穿心莲内酯和栀子苷联合IMP后IMP的MIC变化差异无统计学意义(Z=-1.950~0.000,均P>0.05)。结论黄芩苷同IMP联合对CRKP具有协同作用,同时能降低CRKP对IMP的耐药性。Objective To explore the antibacterial activity of berberine,andrographolide,baicalin,and geniposide combined with imipenem(IMP)against carbapenem-resistant Klebsiella pneumoniae(CRKP)in vitro.Methods Six non-repeating CRKP strains isolated from clinical specimens from January to June 2021 at Mianyang Hospital Affiliated to Chengdu University of Traditional Chinese Medicine were selected.A broth microdilution method was used to determine the minimum inhibitory concentration(MIC)of four Traditional Chinese medicine monomers against six strains of CRKP.MICs of each of the four Traditional Chinese medicine monomers combined with IMP were determined using the checkerboard method against CRKP.The fractional inhibitory concentration(FIC)index was calculated.wilcoxon rank sumtest of two independent samples was used to compare the changes of MIC before and after drug combination in each group.Results Bernerine,andrographolide,baicalin,and geniposide had MICs of 2500μg/ml,2500μg/ml,5000~10000μg/ml,and more than 10000μg/ml to CRKP,respectively.It was found that baicalin and IMP had FICs that ranged from 0.375 to 0.75 against CRKP,with synergy(3 strains).Berberine,andrographolide,geniposide,and IMP had FICs ranging from 0.625~1.25,without synergy.The combination of baicalin and IMP reduced the MIC value of IMP,and the difference was statistically significant(Z=-2.459,P<0.05).In the combination of berberine,andrographolide,and geniposide with IMP,there was no difference in the MIC value for IMP(Z=-1.950~0.000,all P>0.05).Conclusion In combination with IMP,baicalin has synergistic effects on CRKP and can reduce the resistance of CRKP to IMP.

关 键 词：中药单体 亚胺培南 耐碳青霉烯肺炎克雷伯菌 最低抑菌浓度 

分 类 号：R378.996[医药卫生—病原生物学] R446.5[医药卫生—基础医学]