万古霉素单用及联合用药对耐甲氧西林表皮葡萄球菌的防突变浓度研究

Mutant prevention concentrations of vancomycin alone and in combination against methicillin-resistant staphylococcus epidermidis

目的在体外测定万古霉素单药及分别与利福平、左氧氟沙星、磷霉素联用对耐甲氧西林表皮葡萄球菌（MRSE）的防突变浓度（MPC），为优化抗菌治疗提供理论依据。方法应用肉汤法富集浓度为10^10CFU／ml细菌，琼脂平板倍比稀释法测定上述各药单用及分别与万古霉素联用对10株临床分离MRSE的MPC，上述与万古霉素联用药物浓度为常规用药可以达到的血药浓度，均远低于各自对MRSE的MPC。结果万古霉素单药对上述10株MRSE的MPC为16或32mg／L；与利福平或左氧氟沙星联用时万古霉素的MPC为16或32mg／L，与磷霉素联用时万古霉素的MPC降为1～4mg／L。结论与磷霉素联用可以显著降低万古霉素对MRSE的MPC，从而减少耐药菌的产生。

Objective To determine the mutant prevention concentrations （MPCs） of vancomycin alone and in combination with ri- fampicin, levofloxacin or fosfomycin against methicillin-resistant staphylococcus epidermidis （MRSE） in vitro and provide evidence for optimal antimicrobial therapy. Methods Bacterial suspension of 10^19 CFU/ml was enriched in broth. Mutant prevention concentrations of antibiotics in- dividually and in combination with vancomycin against 10 strains of MRSE were determined using agar doubling-dilution method. The concen- trations of antibiotics used in combination with vancomycin reflected achievable serum concentrations and were all lower than respective MPCs against MRSE. Results The MPCs of vancomycin alone against 10 strains of MRSE were 16 or 32 mg/L. The MPCs of vancomycin were 16 or 32 mg/L when combined with levofloxacin or rifampicin. In contrast, the MPCs of vancomycin were 1-4 mg/L when combined with fosfomycin. Conclusion Combined application of vancomycin with fosfomycin can lower the MPCs of vancomycin against MRSE and decrease the emer- gence of resistant strains.