氟苯尼考联合多西环素缩小猪源大肠杆菌耐药突变选择窗

为使临床合理使用抗菌药物，防止细菌耐药性的产生提供理论依据。本研究探讨在体外初步联合氟苯尼考和多西环素缩小猪源大肠杆菌耐药突变选择窗（MSW）。应用琼脂二倍稀释法，肉汤法富集10^11：FU/mL细菌分别测定了氟苯尼考、多西环素对15株猪源大肠杆菌临床分离株的最小抑菌浓度（MIC）、防耐药突变浓度（MPC），并计算出它们各自的MSW，对于2种药物MSW均比较大的菌株S8、S11、S12进行氟苯尼考联合多西环素用药，测定其MPC和MSW。结果显示，从吉林省分离的15株猪源大肠杆菌对氟苯尼考、多西环素耐药率分别为33．3％和46．7％；MPC大于100mg／L的分别占到40％和13．3％；MSW大于50的分别占40％和0．067％。对于S8、S11、S12氟苯尼考联合多西环素用药，联合指数分别为0．75、0．09、0．438，均呈现相加或协同作用。联合用药可使氟本尼考对S8、S11、S12菌株的MPC分别由原来的256．0、128．0、460．8mg／L，变为8．0、8．0、16．0mg／L，均关闭了MSW。结果表明，氟苯尼考联合多西环素可以缩小或关闭猪源大肠杆菌耐药选择突变窗。

Narrowing mutant selection window of swine Enterococci by combined florfenicol with doxycycline in vitro

To develop strategies for reducing drug resistance development and provide rational ap- plication guidelines for available antibacterial medicines in clinic practice, the effect of combination use of florfenicol and doxycycline on mutant selection window （MSW） of single drug group in vitro was investigated. Minimal inhibitory concentration （MIC）,mutant prevention concentration （MPC） and MSWs were determined by agar double dilution method and spreading 10% CFU/mI. coccus on agar plates at different drug concentration for florfenicol, doxycycline. The MPC and MSWs of S8,S11 and S12,of with for these two drugs are both relatively large were determined by florfenicol combined with doxycycline. The resistant rates of 15 strains swine Enterococci from Jilin province were 33. 3% and 46. 7% far florfenicol,doxycycline,above 100 mg/L MPC were 40% and 13.3%,and above 50 mg/L MSWs accounted for 40% and 0.067%,respectively. The combination index of florfenicol and doxycycline for S8,S11 ,S12 were 0. 75,0. 09,0. 438,resptc- tively, showing additive or synergistic effects. For florfenicol, MPC become from 256,128,460.8 mg/I., to 8.0,8. 0 and 16 mg/L. Mutation select window were all closed. The results showed that ：Florfenicol combined with doxycycline factors could reduce or close swine Enterococci resist- ant mutations select window.