摘要：目的 體外研究萬古霉素(vancomycin,VAN)分別與左氧氟沙星(levofloxacin,LVX)、利福平(rifampincin,RFP)、磷霉素(fosfomycin,FOM)聯用對降低對金黃色葡萄球菌防耐藥突變濃度(MPC)的比較,為指導臨床聯合應用抗菌藥物,制定新的用藥策略,防止細菌耐藥產生提供理論依據.方法 采用肉湯富集1010CFU/mL金黃色葡萄球菌ATCC29213,采用瓊脂平板二倍稀釋法測定單獨用藥的最低抑菌濃度(MIC),瓊脂平板稀釋法測定單獨應用VAN以及與其他三種藥物聯用對金黃色葡萄球菌ATCC29213的MPC.并計算出各藥單獨應用的MSW(MPC/MIC).結果 VAN、LVX、RFP、FOM單藥對金黃色葡萄球菌ATCC29213的MIC分別為1,0.125,0.008和2μg/mL; MPC分別為64,2,＞32,64μg/mL,MSW為64,6,＞4000,32.聯合用藥后各藥的MPC(μg/mL)降低程度如下:VAN+LVX (MPCNVA-4,MPCLVX-0.125),VAN+RFP(MPCNVA-4,MPCRFP-0.008),VAN+FOM(MPCNVA -1,MPCFOM-2).聯合LVX和RFP可使VAN的MPC降至原來的1/16倍,聯合FOM可使VAN的MPC降至原來的1/64倍.結論 VAN與另三種藥物聯用,可以明顯降低各自單獨用藥對金黃色葡萄球菌ATCC29213的MPC,其中聯合FOM降低其MPC幅度最大,縮小其MSW效果最好.%Objective To study the comparison of Vancomycin (VAN) separately combined with levofloxacin (LVX), rifampincin (RFP) and fosfomycin (FOM) for decreasing mutant prevention concentration (MPC) of Staphylococcus aureus in vitro, which direct rational applications of available antibiotics in clinic practice and provide evidence for new strategies for restricting the development of resistance. Methods The Staphylococcus aureus strain ATCC29213 was enriched the concentration to 1010 colony forming units per milliliter in broth. Minimum inhibitory concentration (MIC) of VAN, LVX, RFP and FOM alone was determined by agar plates dilution method. Mutant prevention concentration (MPC) of each single and combined was carried out by agar plates dilution method.Then mutant selection window(MSW) could be caculated. Results MIC of VAN, LVX, RFP and FOM for Staphylococcus aureus strain ATCC29213 separately were 1, 0.125, 0.008, 2ug/mL; MPC of these four antibiotics alone were 64, 2, >32, 64 μg/mL; and MSW(MPC/MIC) of each antibiotic were 64, 16, >4000, 32; after combinated MPC(μg/mL) of each alone were decreased as fllows: VAN+LVX (MPCNVA-4 , MPCLVX-0.125), VAN+RFP(MPCNVA-4, MPCRFP -0.008), VAN+FOM(MPCNVA -1, MPCFOM -2 ). MPCNVA of VAN combined with LVX can decreaseto 1/16 times of VAN used alone. MPCNVA of VAN combined with RFP can decrease to 1/16 times of it used alone either. MPCNVA of VAN combined with FOM can decrease to 1/64 times of it used alone. Conclusion Compared with each one alone, the combination of VAN separately with other three antibiotics can obviously decrease MPCVAN. The combination of VAN and FOM was more evidently in dropping MPCNVA of Staphylococcus aureus strain ATCC29213 and narrowing MSW of VAN.