克拉霉素联用头孢呋辛对金黄色葡萄球菌预防耐药突变浓度的影响  

Effects of combination of clarithromycin and cefuroxime sodium on mutant prevention concentration of Staphylococcus aureus

作　　者：蒙小菲 杨玉芳[1] 钟小斌[1] 邹小琴[1] 李萌[1] 覃巧[1] 张文宇[1] 

机构地区：[1]广西医科大学第一附属医院药学部,广西南宁530021

出　　处：《中华医院感染学杂志》2016年第13期2902-2905,共4页Chinese Journal of Nosocomiology

基　　金：国家自然科学基金资助项目(No 81260598;81560729);广西医疗卫生适宜技术研究与开发基金资助项目(S201302-03)

摘　　要：目的在体外探讨克拉霉素(CLR)、头孢呋辛(CXM)单用及合用对金黄色葡萄球菌的抗菌作用和预防耐药突变的能力。方法采用琼脂平板倍比稀释法和棋盘法分别测定CLR、CXM单用及联用时对金黄色葡萄球菌的最小抑菌浓度(MIC),并计算联合指数(FIC);肉汤法富集1010 CFU/ml金黄色葡萄球菌,采用琼脂平板倍比稀释法和简易棋盘法测定单用及联用时预防耐药突变浓度(MPC),并计算相应的选择指数(SI)。结果 CLR单药对金黄色葡萄球菌的MIC、MPC、SI分别是4.0μg/ml、25.6μg/ml、6.4;CXM单药对金黄色葡萄球菌的MIC、MPC、SI分别为4.0μg/ml、51.2μg/ml、12.8,CLR和CXM两药联用对金黄色葡萄球菌的MIC均为4.0μg/ml,联合指数(FIC)为2.0,两药联用的体外抗菌效果为无关作用,联合应用使CLR的MPC由单独使用时的25.6μg/ml下降为8.0μg/ml,SI由单独使用时的6.4下降到联用后的2.0;同时联合应用使CXM的MPC由单独使用时的51.2μg/ml下降为8.0μg/ml,SI由单独使用时的12.8下降到联用后的1.0,当CLR、CXM均达到8.0μg/ml时便可抑制耐药突变体的产生。结论 CLR、CXM联用时,可降低单独用药对金黄色葡萄球菌的MPC和SI,增强预防耐药突变体产生的能力。OBJECTIVE To study the antibacterial effect and the mutant prevention ability of Clarithromycin（CLR）,Cefuroxime sodium（CXM）separately and jointly against Staphylococcus aureus in vitro.METHODS The minimal inhibitory concentrations（MIC）of CLR and CXM against Staphylococcus aureus were determined by agar plate dilution method when they were used separately and by chess board method when they were used in combination.The fractional inhibitory concentrations（FIC）were then calculated.The 10^10 CFU/ml Staphylococcus aureus was enriched by meat infusion culture-medium and the mutant prevention concentrations（MPC）were determined by agar plate dilution method and simple chess board method.The corresponding selection index SI（MPC/MIC）was then calculated.RESULTS The MIC,MPC and SI of CLR were 4.0μg/ml,25.6μg/ml,and 6.4.The MIC,MPC and SI of CXM were 4.0μg/ml,51.2μg/ml,12.8.When used in combination,the MIC of CLR and CXM was 4.0μg/ml and indifferent effect（FIC）was 2.0,and had irrelevant effect.The MPC of CLR decreased from25.6μg/ml when it was used alone to 8.0μg/ml when it was combined with CXM,and the SI reduced from 6.4when it was used alone to 2.0after combination with CXM.The MPC of CXM decreased from 51.2μg/ml when it used alone to 8.0μg/ml when it was combined with CLR,and the SI decreased from 12.8when it was used alone to 1.0after combination with CLR.When CLR and CXM were combined and each of them reached the value of 8.0μg/ml,it could inhibit the generation of resistant mutants.CONCLUSION The combination of CLR and CXM can reduce the MPC and SI of Staphylococcus aureus and enhance the ability of anti drug resistant mutants.

关 键 词：克拉霉素 头孢呋辛 金黄色葡萄球菌 预防耐药突变浓度 选择指数 

分 类 号：R378.11[医药卫生—病原生物学]