硫酸头孢喹肟联合甲氧苄啶作用下金黄色葡萄球菌体外药效及适应性耐药研究  

Study on the efficacy and adaptive resistance of Staphylococcus aureus under the action of cefquinome sulfate combined with trimethoprim in vitro

作　　者：朱昊 韦起壮 陈云[1] 陈杰茹 何晓涛 韩蒙蒙 多水银 杨雨辉[1] ZHU Hao;WEI Qizhuang;CHEN Yun;CHEN Jieru;HE Xiaotao;HAN Mengmeng;DUO Shuiyin;YANG Yuhui(Key Lahoratory of Tropical Animal Reproduction and Disease Research of Hainan Province,School of Animal Science and Technology,Hainan University,Haikou 570100,China)

机构地区：[1]海南大学动物科技学院海南省热带动物繁殖与疫病研究重点实验室,海口570100

出　　处：《黑龙江畜牧兽医》2021年第17期1-5,共5页Heilongjiang Animal Science And veterinary Medicine

基　　金：海南省自然科学基金项目(ZDYF2019098)。

摘　　要：为了探究体外硫酸头孢喹肟联合甲氧苄啶对金黄色葡萄球菌突变选择窗的影响,以及判断金黄色葡萄球菌经硫酸头孢喹肟与甲氧苄啶联合诱导后在体外是否发生适应性耐药,试验采用微量肉汤稀释法和棋盘稀释法分别测定硫酸头孢喹肟和甲氧苄啶单药及联合用药后的最小抑菌浓度(MIC),并计算其分级抑菌浓度(FIC)指数;采用平板稀释法和交叉法分别测定单药及联合用药后的防突变浓度(MPC),并计算其突变选择窗(MSW)范围;之后通过PK/PD体外模型诱导金黄色葡萄球菌,采用平板菌落计数法测定细菌数量变化和突变频率。结果表明:单药硫酸头孢喹肟、甲氧苄啶对金黄色葡萄球菌的MIC分别为0.5μg/mL和256μg/mL,联合用药后分别降低至0.125μg/mL和64μg/mL。硫酸头孢喹肟联合甲氧苄啶后的FIC指数为0.5,两种药物联合表现为协同作用。单独用药时,硫酸头孢喹肟的MPC为1.6μg/mL,MSW的范围为0.5~1.6μg/mL;联合用药时,硫酸头孢喹肟的MPC降低至0.5μg/mL,MSW的范围缩小为0.125~0.5μg/mL。当消除半衰期为2.5 h时,模型流量为1.372 6 mL/min,蠕动泵频率为20 r/min。金黄色葡萄球菌在经过不同药物浓度的PK/PD体外模型诱导后,细菌突变频率呈逐渐递增趋势,均出现适应性耐药。说明硫酸头孢喹肟联合甲氧苄啶后可降低硫酸头孢喹肟单药对金黄色葡萄球菌的MPC,缩小耐药MSW范围,并且证实金黄色葡萄球菌在硫酸头孢喹肟联合甲氧苄啶诱导后可发生适应性耐药现象。The aim of the present study was to investigate the effect of cefquinome sulfate combined with trimethoprim on mutant selection window of Staphylococcus aureus in vitro, and to determine whether adaptive resistance of Staphylococcus aureus induced by the combination of cefquinome sulfate and trimethoprim occurred in vitro. The minimal inhibitory concentrations(MIC) of cefquinome sulfate and trimethoprime were determined by microbroth dilution method and chessboard dilution method, respectively, and the fractional inhibitory concentration(FIC) index was calculated. The mutant prevention concentration(MPC) of single drug and combination drug were determined by plate dilution method and cross method, and the range of mutation selection window(MSW) was calculated. Staphylococcus aureus was induced by PK/PD model in vitro, and the change of bacteria number and mutation frequency were measured by plate colony counting method. The results showed that the MICs of single drug cefquinome sulfate and trimethoprime against Staphylococcus aureus were 0.5 μg/mL and 256 μg/mL, respectively, and decreased to 0.125 μg/mL and 64 μg/mL after combined administration, respectively. The FIC index of cefquime sulfate combined with trimethoprime was 0.5. Combined administration of the two drugs showed synergistic effect. MPC and MSW of cefquime sulfate were 1.6 μg/mL and 0.5-1.6 μg/mL respectively when single administration was used. In combination administration, the MPC of cefquime sulfate was reduced to 0.5 μg/mL, and the MSW range was reduced to 0.125-0.5 μg/mL. When the elimination half-life is 2.5 h, the model flow rate is 1.372 6 mL/min, and the peristaltic pump frequency is 20 r/min.Staphylococcus aureus was induced by PK/PD model with different concentrations of drugs in vitro, and the mutation frequency of bacteria showed a gradually increasing trend, and all of them showed adaptive drug resistance. These results indicated that the cefquinome sulfate combined with trimethoprime could reduce the MPC of single drug of ce

关 键 词：硫酸头孢喹肟 甲氧苄啶 金黄色葡萄球菌 突变选择窗 PK/PD体外模型 适应性耐药 

分 类 号：S859.796[农业科学—临床兽医学]