IN-VITRO AND IN-VIVO EVALUATIONS OF A-80556, A NEW FLUOROQUINOLONE

A-80556 is a novel fluoroquinolone with potent antibacterial activity against gram-positive, gram-negative, and anaerobic organisms. A 80556 was more active than ciprofloxacin, ofloxacin, lomefloxacin, and sparfloxacin against gram-positive bacteria. A-80556 was particularly active against Staphylococcus aureus (MIC for 90% of isolates [MIC(90)], 0.12 mu g/ml, relative to fluoroquinolone-susceptible strains) and Streptococcus pneumoniae (MIC(90), 0.12 mu g/ml). A-80556 was also the most active of the quinolones tested against ciprofloxacin-resistant S. aureus, with an MIC(90) of 4.0 mu g/ml; that of ciprofloxacin was > 128 mu g/ml. However, the significance of this activity is not known. A-80556 was slightly less active against Escherichia coli (MIC(90), 0.06 mu g/ml) and other enteric organisms than ciprofloxacin (MIC(90) for E. coli, less than or equal to 0.03 mu g/ml). A-80556 was slightly less active against Pseudomonas eruginosa (MIC(90), 4.0 (mu g/ml) than ciprofloxacin (MIC(90), 2.0 mu g/ml) and more active against Acinetobacter spp. (respective MIC(90)s, 0.12 and 0.5 (mu g/ml). A-80556 was also the most active compound against anaerobes. Against Bacteroides fragilis, the MIC(50) of A-80556 was 2.0 mu g/ml; that of ciprofloxacin was 16 mu g/ml. The in vivo efficacy of A-80556 in experimental models with both gram-positive and gram-negative infections was consistent with the in vitro activity and pharmacokinetics and oral absorption in mice.