Study For Influence Of Mutant Selection Window Of Staphylocococus Aureus By Single And Combination Of Fluoroquinolones In Vitro

Objective:To detect the capacity of single levofloxacin or moxiflo- xacin and combined with cephazoline in restricting the development of resistant mutants in strains of the clinic isolated ciprofloxacin and oxacillin-susceptible Staphylococcus aureus(SA) by determining mutant prevention concentration (MPC), to compare MPC and MPC/MIC( selective index, SI), and to investigate the effect of the drug combination on the mutant selection window(MSW) in vitro, to guide clinicians using antibiotics rationally, and to provide the theoretical dependence on preventing drug resistance.Methods:The minimal inhibitory concentrations (MIC) of 1evoflo- xacin ,moxifloxacin and cephazoline for staphylococcus aureus and quality control (ATCC25923)were determined by the standard two fold agar dilution methods. The cells of 10 10colony forming units per milliliter staphylococcus were enriched in broth .The MPC of fluoroquinolones against strains were determined by spreading 10 10cfu/ml coccus on containing single and two drugs agar plates at different concentrations. Inoculated plates were incubated for 72h.The MPC recorded as the lowest fluoroquinolone concentration completely inhibiting bacterial growth at this time. The values of MIC50, MIC90, MPC50, MPC90 and MPC/MIC were calculated. Using the SPSS statistics software to analyze the data.Results: (1)MPC values of single levofloxacin and moxifloxacin were 2-64 mg/L and 0.25-16 mg/L respectively for thirty clinic isolated ciprofloxacin and oxacillin-susceptible Staphylococcus aureus, those of combined with cephazoline were 0.5- 16mg/L,0.125-4 mg/L.(2)MPC90 of single moxifloxacin (4mg/L) was significant lower than that of levofloxacin(32mg/L) .( 3) Combined with cephazoline the MPC90 of levofloxacin decreased from 32mg/L(single drug)to 8 mg/L ; MPC90 of single moxifloxacin was 8 mg/L and combined with cephazoline it decreased to 1 mg/L. ( 4 ) MPC90/MIC90 of single levofloxacin and moxifloxacin were 8 and 4, and those of combined with cephazoline decreased to 2 and 1. The significative differences were detected in single fluoroquinolone group and combined cephazoline group. (5)After combin- ation,MPC90 and MPC90/MIC90 value in moxifloxacin were significant lower than that in levofloxacin.Conclusions: Moxifloxacin exhibited lower MPC, narrower MSW, higher ability of resistant mutants for in strains of the clinic isolated ciprofloxacin and oxacillin-susceptible SA, and was lower drug resistanct development and safe drug. Levofloxacin combined with cephazoline could decrease MPC, narrower MSW. Moxifloxacin combined with cephazoline could decrease MPC, and made it equal to MIC. This study indicated that drug combination may narrow or even close the MSW which single fluoroquinolone produced, reduce the selective enrichment of resistant mutants, and prevent drug resistant development.