IN-VITRO AND IN-VIVO ANTIBACTERIAL EFFICACIES OF CFC-222, A NEW FLUOROQUINOLONE

CFC-222 is a novel fluoroquinolone containing a C-7 bicyclic amine moi ety with potent antibacterial activities against gram-positive, gram n egative, and anaerobic organisms, We compared the in vitro and in vivo activities of CFC-222 with those of ciprofloxacin, ofloxacin, and lom efloxacin. CFC-222 was more active than the other fluoroquinolones tes ted against gram-positive bacteria, CFC-222 was particularly active ag ainst Streptococcus pneumoniae (MIC at which 90% of isolates are inhib ited [MIC90], 0.2 mu g/ml), Staphylococcus aureus (MIC90, 0.2 mu g/ml for ciprofloxacin-susceptible strains), and Enterococcus faecalis (MIC 90, 0.39 mu g/ml). Against Escherichia coli and other members of the f amily Enterobacteriaceae, CFC-222 was slightly less active than ciprof loxacin (MIC(90)s for E. coli, 0.1 and 0.025 mu g/ml, respectively), T he in vitro activity of CFC-222 was not influenced by inoculum size, m edium composition, or the presence of horse serum, However, its activi ty was decreased significantly by a change in the pH of the medium fro m 7.0 to 6.0, as was the case for the other quinolones tested, The in vivo protective efficacy of CFC-222 by oral administration was greater than those of the other quinolones tested in a mouse model of intrape ritoneally inoculated systemic infection caused by S. aureus, CFC-222 exhibited efficacy comparable to that of ciprofloxacin in the same mod el of infection caused by gram-negative organisms, such as E. coli and Klebsiella pneumoniae. In this infection model, CFC-222 was slightly less active than ciprofloxacin against Pseudomonas aeruginosa. These r esults suggest that CPC-222 may be a promising therapeutic agent in va rious bacterial infections.