Abstract: OBJECTIVE To study the antibacterial effect and the mutant prevention ability of Clarithromycin (CLR), Cefuroxime sodium (CXM) separately and jointly against Staphylococcus aureus in vitro. METHODS The minimal inhibitory concentrations(MIC) of CLR and CXM against Staphylococcus aureus were determined by agar plate dilution method when they were used separately and by chess board method when they were used in combination. The fractional inhibitory concentrations(FIC) were then calculated. The 10¹⁰ CFU/ml Staphylococcus aureus was enriched by meat infusion culture-medium and the mutant prevention concentrations(MPC) were determined by agar plate dilution method and simple chess board method. The corresponding selection index SI(MPC/MIC) was then calculated. RESULTS The MIC, MPC and SI of CLR were 4.0 μg/ml, 25.6 μg/ml, and 6.4. The MIC, MPC and SI of CXM were 4.0 μg/ml,51.2 μg/ml,12.8. When used in combination, the MIC of CLR and CXM was 4.0 μg/ml and indifferent effect (FIC) was 2.0, and had irrelevant effect. The MPC of CLR decreased from 25.6 μg/ml when it was used alone to 8.0 μg/ml when it was combined with CXM, and the SI reduced from 6.4 when it was used alone to 2.0 after combination with CXM. The MPC of CXM decreased from 51.2 μg/ml when it used alone to 8.0 μg/ml when it was combined with CLR, and the SI decreased from 12.8 when it was used alone to 1.0 after combination with CLR. When CLR and CXM were combined and each of them reached the value of 8.0 μg/ml, it could inhibit the generation of resistant mutants. CONCLUSION The combination of CLR and CXM can reduce the MPC and SI of Staphylococcus aureus and enhance the ability of anti drug resistant mutants.