The in vitro and in vivo antibacterial activities of
KB-5246, a tetracyclic
quinolone, were compared with those of
ciprofloxacin,
ofloxacin, and
norfloxacin.
KB-5246 demonstrated a broad antibacterial spectrum. The in vitro activity of
KB-5246 against gram-negative bacteria was higher than that of
ofloxacin or
norfloxacin and was comparable to that of
ciprofloxacin.
KB-5246 demonstrated the greatest activity against gram-positive bacteria of the four agents tested. Among Streptococcus pyogenes strains resistant to 1.56 micrograms of
norfloxacin per ml, there were 26 strains susceptible to 0.2 micrograms of
KB-5246 per ml. Similarly, among the Staphylococcus aureus and Staphylococcus epidermidis strains resistant to 3.13 micrograms of
norfloxacin per ml, there were 23 S. aureus and 11 S. epidermidis strains susceptible to 0.39 micrograms of
KB-5246 per ml. Among the Streptococcus pneumoniae and Enterococcus faecalis strains resistant to 12.5 micrograms of
norfloxacin per ml, there were 5 S. pneumoniae and 10 E. faecalis strains susceptible to 0.39 micrograms of
KB-5246 per ml.
KB-5246 had bactericidal activity at the MIC.
KB-5246 demonstrated excellent antibacterial activity against various systemic
infections in mice. After
oral administration,
KB-5246 was as active as
ofloxacin and about two times more active than
norfloxacin.