西他沙星与莫西沙星抑制细胞内外金黄色葡萄球菌的活性研究

Activity of sitafloxacin and moxifloxacin against extracellular and intracellular Staphylococcus aureus in vitro and in vivo

目的对西他沙星与莫西沙星抑制细胞内外金黄色葡萄球菌的活性进行体内外研究,从而更好地指导临床用药,降低细菌耐药性。方法本研究选用金黄色葡萄球菌ATCC25923,采用微量肉汤稀释法检测药物的MIC,MBC及MPC;构建新型巨噬细胞RAW264.7细菌感染模型,检测体外药物的胞内外活性;构建药物胞内蓄积模型,采用HLPC检测胞内药物含量;构建小鼠腹腔巨噬细胞细菌感染模型,采用琼脂平板稀释法检测药物时间及浓度杀菌曲线。结果在体外实验中,MIC,MBC,MPC及时间与浓度杀菌曲线实验表明西他沙星胞内外抑菌活性均强于莫西沙星;在体内试验中,结果表明细胞内药物活性取决于给药频率及药物浓度,同时得出药物胞内含量与胞内活性并非一致。通过药物时间与浓度胞内外杀菌曲线测定,得出西他沙星的抑菌活性强于莫西沙星。结论体内外研究表明西他沙星抑制细胞内外金黄色葡萄球菌的活性强于莫西沙星,能够更好的用于临床治疗。

Objective To determine extracellular and intracellular activities of sitafloxacin and moxifloxacin against Staphylococcus aureus （ATCC25923） in vivo and in vitro. Methods MIC, MBC and MPC were determined by microdilution in broth, intracellular activity was determined after phagocytosis by RAW264.7 cells. Cellular quinolones accumulation was determined by HPLC. Time- and concentration-kiU relationships were examined in vitro and in vivo using a mouse peritonitis model. Results The in broth activities of sitafloxacin, including the MIC, MBC, MPC and the intra- and extracellular time- and concentration- kill relationships, were greater than that of moxifloxacin. It showed that the dominant factor during testing of intracellular activity in vivo was the frequency of doses. There was a poor correlation between the intracellular accumulation and the actual intracellular effect of the two different quinolones. The results indicated that sitafloxacin has the potential to display useful activity against extracellular and intracellular S. aureus. Conclusions Sitafloxacin is active against both extracellular and intracellular Staphylococcus aureus, and is more effective than moxifloxacin.