头孢喹肟分别与3种抗生素联用对金黄色葡萄球菌突变选择窗的影响研究
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摘要
为了探讨体外头孢喹肟联合恩诺沙星、庆大霉素、卡那霉素对金黄色葡萄球菌突变选择窗(MSW)的影响,试验采用微量肉汤稀释法和棋盘稀释法测定药物单用及联用的最小抑菌浓度(MIC),并计算分级抑菌浓度(FIC)指数;采用琼脂二倍稀释法和交叉法测定单药及联用的防突变浓度(MPC),并计算MSW范围。结果表明:头孢喹肟、恩诺沙星、庆大霉素、卡那霉素对金黄色葡萄球菌ATCC6538的MIC分别为0.50,0.25,0.50,2.00μg/mL;MPC分别为1.60,4.00,2.00,4.19μg/mL;MSW范围分别为0.50～1.60,0.25～4.00,0.50～2.00,2.00～4.19μg/mL。头孢喹肟与恩诺沙星联用后的FIC指数为0.50,MSW范围分别缩小至0.125～0.25和0.062 5～2.00μg/mL;与庆大霉素联用后的FIC指数为1.00,MSW分别缩小至0.25～1.00和0.25～1.00μg/mL;与卡那霉素联用后的FIC指数为1.00,MSW分别缩小至0.25～1.00和1.00～2.00μg/mL。说明头孢喹肟和恩诺沙星、庆大霉素、卡那霉素合用可以缩小MSW范围,减少耐药性的发生。
To investigate the effects of cefquinome combined with enrofloxacin, gentamicin, kanamycin respectively on the mutant selection window(MSW) against Staphylococcus aureus, the minimal inhibitory concentrations(MIC) of cefotaxime individual and in combination with three antibiotics were determined by broth micro dilution method and the checkerboard method. The fractional inhibitory concentration(FIC) indexes were calculated in addition. The mutant prevention concentration(MPC) of individual and in combination were determined by the agar plate dilution method and bracketing method. Then the MSW were calculated.The results showed that the MIC of cefotaxime, enrofloxacin, gentamicin, kanamycin were 0.50, 0.25, 0.50, 2.00 μg/mL, MPC were 1.60, 4.00, 2.00, 4.19 μg/mL. The ranges of MSW were 0.50-1.60, 0.25-4.00, 0.50-2.00, 2.00-4.19 μg/mL, respectively. The FIC index of cefquinome combined with enrofloxacin was 0.50,and the ranges of MSW were reduced to 0.125-0.25 and 0.062 5-2.00 μg/mL respectively. In combination with gentamicin, the FIC index was 1.00 and the MSW were reduced to 0.25-1.00 and 0.25-1.00 μg/mL respectively. Combined with kanamycin, the FIC index was 1.00, and the MSW were reduced to 0.25-1.00 and 1.00-2.00 μg/mL, respectively. The results indicate that cefquinome in combination with enrofloxacin, gentamicin, kanamycin can decrease the ranges of MSW and avoid the appearance of resistance.
To investigate the effects of cefquinome combined with enrofloxacin, gentamicin, kanamycin respectively on the mutant selection window(MSW) against Staphylococcus aureus, the minimal inhibitory concentrations(MIC) of cefotaxime individual and in combination with three antibiotics were determined by broth micro dilution method and the checkerboard method. The fractional inhibitory concentration(FIC) indexes were calculated in addition. The mutant prevention concentration(MPC) of individual and in combination were determined by the agar plate dilution method and bracketing method. Then the MSW were calculated.The results showed that the MIC of cefotaxime, enrofloxacin, gentamicin, kanamycin were 0.50, 0.25, 0.50, 2.00 μg/mL, MPC were 1.60, 4.00, 2.00, 4.19 μg/mL. The ranges of MSW were 0.50-1.60, 0.25-4.00, 0.50-2.00, 2.00-4.19 μg/mL, respectively. The FIC index of cefquinome combined with enrofloxacin was 0.50,and the ranges of MSW were reduced to 0.125-0.25 and 0.062 5-2.00 μg/mL respectively. In combination with gentamicin, the FIC index was 1.00 and the MSW were reduced to 0.25-1.00 and 0.25-1.00 μg/mL respectively. Combined with kanamycin, the FIC index was 1.00, and the MSW were reduced to 0.25-1.00 and 1.00-2.00 μg/mL, respectively. The results indicate that cefquinome in combination with enrofloxacin, gentamicin, kanamycin can decrease the ranges of MSW and avoid the appearance of resistance.
引文
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[9] 徐丽丽, 陈春林, 刘桢宇, 等. 夫西地酸联合头孢类抗生素缩小金黄色葡萄球菌耐药突变选择窗的研究 [J]. 中国临床药理学与治疗学, 2016, 21(9): 995-1000.
[10] 贾宏军, 郑晓辉, 赵振营. 新版《抗菌药物临床应用指导原则》 (2015) 的解读 [J]. 天津药学, 2016, 28(5): 46-48.
[11] 刘美端, 赵地顺, 刘宝树, 等. 头孢喹肟研究进展 [J]. 中国畜牧兽医, 2013, 40(4): 216-221.
[12] 叶建美, 吴康, 吴洪丽, 等. 恩诺沙星抗菌效果及药代动力学研究进展 [J]. 湖北农业科学, 2015, 54(23): 5813-5816.
[13] 吴波, 段龙川, 罗厚强. 头孢喹诺与恩诺沙星联合用药对黄羽肉鸡常见病原菌的药敏试验 [J]. 浙江农业科学, 2015, 56(6): 949-951.
[14] 简心韵, 邓子新, 孙宇辉. 氨基糖苷抗生素庆大霉素:基础研究的新进展及应用研究的新潜力 [J]. 生物工程学报, 2015, 31(6): 829-844.
[2] XIONG M, WU X, YE X, et al. Relationship between cefquinome pk/pd parameters and emergence of resistance of Staphylococcus aureus in rabbit tissue-cage infection model [J]. Front Microbiol, 2016, 7: 874.
[3] SUN W, WEINGARTEN R A, XU M, et al. Rapid antimicrobial susceptibility test for identification of new therapeutics and drug combinations against multidrug-resistant bacteria [J]. Emerg Microbes Infect, 2016, 5(11): e116.
[4] 吴昊. 浓度及时间依赖型代表药物在体外PK/PD模型内对敏感菌耐药性产生和富增影响的研究 [D]. 海口: 海南大学,2014.
[5] 常超越, 张召兴, 闫艳娟, 等. 致雏鸡腹泻病原的分离鉴定与药敏试验 [J]. 中国兽医杂志, 2017, 53(11): 48-50.
[6] 宋美英, 张承欢, 只勇, 等. 头孢噻呋单用及联合甲氧苄啶对致病性牛源大肠杆菌防突变浓度的研究 [J]. 黑龙江畜牧兽医, 2017 (03上): 11-14.
[7] 全岩. 沙拉沙星及与安普霉素联用的体外抗菌后效应研究 [J]. 今日畜牧兽医, 2018, 34(2): 8-10.
[8] 夏文颖, 梅亚宁, 顾兵, 等. 头孢哌酮/舒巴坦联合美罗培南对鲍曼不动杆菌体外抗菌作用研究 [J]. 中国临床药理学杂志, 2014, 30(12): 1127-1129.
[9] 徐丽丽, 陈春林, 刘桢宇, 等. 夫西地酸联合头孢类抗生素缩小金黄色葡萄球菌耐药突变选择窗的研究 [J]. 中国临床药理学与治疗学, 2016, 21(9): 995-1000.
[10] 贾宏军, 郑晓辉, 赵振营. 新版《抗菌药物临床应用指导原则》 (2015) 的解读 [J]. 天津药学, 2016, 28(5): 46-48.
[11] 刘美端, 赵地顺, 刘宝树, 等. 头孢喹肟研究进展 [J]. 中国畜牧兽医, 2013, 40(4): 216-221.
[12] 叶建美, 吴康, 吴洪丽, 等. 恩诺沙星抗菌效果及药代动力学研究进展 [J]. 湖北农业科学, 2015, 54(23): 5813-5816.
[13] 吴波, 段龙川, 罗厚强. 头孢喹诺与恩诺沙星联合用药对黄羽肉鸡常见病原菌的药敏试验 [J]. 浙江农业科学, 2015, 56(6): 949-951.
[14] 简心韵, 邓子新, 孙宇辉. 氨基糖苷抗生素庆大霉素:基础研究的新进展及应用研究的新潜力 [J]. 生物工程学报, 2015, 31(6): 829-844.