Abstract: AIM: To study the correlation of levofloxacin pharmacokinetic/pharmacodynamic parameters with selection of staphylococcus aureus resistance.METHODS: Tissue cage infection model with staphylococcus aureus was established in rabbits, and the infected animals were given levofloxacin intragastrically at various doses.Changes in levofloxacin concentration, levofloxacin susceptibility of bacteria were monitored at the site of infection.RESULTS: AUC₂₄/MIC, AUC₂₄/MPC, C_max/MIC, C_max/MPC, time above MPC and T_msw showed a statistically significant correlation with selection of staphylococcus aureus resistance, and time above MIC did not (MIC :minimal inhibitory concentration, MPC :mutant prevention concentration, MSW :mutant selection window). Loss of bacterial susceptibility occurred easily when AUC₂₄/MIC was between 20 h and 150 h, and keeping AUC₂₄/MPC above 25 h could restrict selection of resistance.The upper boundary of the selection window in vivo was estimated as an AUC₂₄/MPC value of 25 h, and the lower boundary was estimated as an AUC₂₄/MIC value of 20 h.CONCLUSION: AUC₂₄/MPC, C_max/MPC and time above MPC may be the parameters for predicting resistance.

Key words: levofloxacin, pharmacokinetic/pharmacodynamic, staphylococcus aureus, mutant selection window