Abstract
The in vitro and in vivo antibacterial activities of pazufloxacin (PZFX) were compared with those of ciprofloxacin (CPFX), ofloxacin (OFLX), sparfloxacin (SPFX) and tosufloxacin (TFLX).
PZFX showed strong antibacterial activity next to those of SPFX and TFLX against the genus Staphylococcus, including methicillin-resistant Staphylococcus aureus, and its antibacterial activity against the genus Streptococcus was almost equal to those of CPFX and OFLX. Against members of the family Enterobacteriaceae, except for Proteus rettgeri, the MIC90 of PZFX was less than 4μg/ml, a level of activity which was the same as or higher than that of CPFX. For glucose-nonfermentative gram-negative rods, the activity of PZFX was the same as that of CPFX.
As for the influence on the growth curve of Pseudomonas aeruginosa, PZFX showed a strong antibacterial effect within a short time. In addition, PZFX suppressed regrowth 3 hours longer than OFLX in an in vitro pharmacokinetic model which reproduced the changes in human serum concentration.
In systemic infection caused by two strains of Staphylococcus aureus and two of gram-negative rods in mice, the ED50s of PZFX was 0.01-0.32mg/mouse. The therapeutic effects were superior to those of other drugs tested except for SPFX on 2 strains of S. aureus and Klebsiella pneumoniae 3K-25 infection and CPFX on Pseudomonas aeruginosa E7 infection. In respiratory infection caused byK. pneumoniae 3 K-25 and pyelonephritic infection caused by Escherichia coli TMS3 in mice, the therapeutic effects of PZFX were superior to those of other drugs except for SPFX. In P. aeruginosa KU-1 pyelonephritic infection mice, the therapeutic effect of PZFX was most active among the drugs tested.
In a pharmacokinetic study using mice, PZFX rapidly reached the maximum concentration in serum, lung and kidney with the peak values higher than those of control drugs (CPFX, OFLX, SPFX and TFLX). The half-lives of PZFX in serum, lung and kidney were almost equal to those of OFLX.
