Studies on effect of drug concentration on selection of resistant mutants of staphylococcus aureus

AIM:To study the effect of levofloxacin,vancomycin,rifampin,azithromycin,tobramycin and chloramphenicol concentration on selection of resistant mutants of staphylococcus aureus ATCC29213.Also to combine minimal inhibitory concentration(MIC),mutant prevention concentration(MPC)and mutant selection window(MSW)with pharmacokinetic parameters and then provide evidence for new strategies for restricting the development of resistance.METHODS:The agar dilution method was carried out on drug-containing agar according to NCCLS guidelines to determine MIC of levofloxacin,vancomycin,rifampin,azithromycin,tobramycin and chloramphenicol against ATCC29213.MPC was determined by the agar dilution according to MIC determining except that ATCC29213 were enriched in broth,and the bacterial concentrations were adjusted to 1010 colony form units per milliliter.Staphylococcus aureus were plated on agar containing various antimicrobial concentrations.The fraction of bacteria recovered curve was traced by colony counting.RESULTS:The MPCs of levofloxacin,vancomycin,rifampin,azithromycin,tobramycin and chloramphenicol for staphylococcus aureus strain ATCC29213 were 1.4,51.2,1024,4.8,16,and 16 μg/mL;the MICs of them were 0.125,1.0,0.002,0.5,3.0,and 0.5 μg/mL respectively;and the MSW of each antimicrobial-staphylococcus aureus combination was distinct.The MSW of rifampin-staphylococcus aureus was the broadest,and the MSW of chloramphenicol-staphylococcus aureus was the narrowest.The fraction of bacteria recovered curve varied considerably among the bacterium-antimicrobial combinations.CONCLUSION:Antimicrobial concentrations have strong effect on the recovery and selection of resistant colonies.In clinical practice,the selection of resistant mutants could be prevented by choosing antimicrobial concentration and medication in combining MPC with pharmacokinetic parameters.