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Antibiotic activity can differ depending on whether the bacterial target is extracellular or intracellular. To determine extracellular and intracellular activities of sitafloxacin (STX) against Staphylococcus aureus in comparison with levofloxacin (LVX) and moxifloxacin (MXF) in vivo and in vitro, three S. aureus strains (ATCC25923, 29213, 43300) were evaluated. MIC, MBC and mutant prevention concentration (MPC) of the test quinolone for S. aureus were determined by microdilution in broth, and intracellular activity was determined in RAW264.7 cells after phagocytosis of bacteria. Cellular quinolone accumulation was determined by HPLC. The time- and concentration-kill relationships were examined in vitro (in broth and in RAW264.7 cells, respectively) and in vivo by use of a mouse peritonitis model. The results showed that the activity of STX in broth cultures, including the MIC, MBC, MPC and the time- and concentration-kill relationships, were greater for STX than those for LVX and MXF. In particular, STX exhibited the strongest activity against intramacrophage S. aureus. The intracellular effects could be ranked in the following order as the mean change in the log10 number of cfu ml(-1) (log10 cfu ml(-1)) between treated and untreated mice: STX&gt;LVX&gt;MXF. It also showed that the dominant factor of intracellular activity in vivo was the frequency of doses. There was a poor correlation between the intracellular accumulation of the three different quinolones and the actual intracellular effect. The results of the intracellular and extracellular time- and concentration-kill relationships indicated that STX has the potential to display useful activity against extracellular and intracellular S. aureus.

journal of antibiotics

Activity of sitafloxacin against extracellular and intracellular Staphylococcus aureus in vitro and in vivo: comparison with levofloxacin and moxifloxacin