IN-VITRO ACTIVITY OF BAY-12-8039, A NEW 8-METHOXYQUINOLONE

BAY 12-8039 is a new 8-methoxyquinolone with antibacterial activity ag ainst gram-positive bacteria which is significantly better than those of sparfloxacin or ciprofloxacin. The minimal inhibitory concentration s (MICs) for 90% of methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis were 0.062 and 2 mg/l, respectively. The MI C(90)s for ciprofloxacin-resistant, methicillin-susceptible and methic illin-resistant S. aureus were 8 mg/l. Against the staphylococcal stra ins tested sparfloxacin was 2-fold and ciprofloxacin greater than or e qual to 10-fold less active. MIC(90)s for Streptococcus pneumoniae, St reptococcus pyogenes and Streptococcus agalactiae were 0.125-0.5 mg/l, irrespective of whether strains with diminished ciprofloxacin suscept ibility or ciprofloxacin-susceptible strains were tested. Against the streptococci sparfloxacin was 2- to 4- fold less active. Against gram- negative bacteria BAY 12-8039 is almost as active as ciprofloxacin, ex cept for Pseudomonas aeruginosa. Against Bacteroides fragilis, Bactero ides spp. and Clostridium spp. BAY 12-8039 was as active as metronidaz ole. The bactericidal activity against S. aureus and S. pneumoniae was in contrast to that of the other quinolones tested, penicillin G, amo xicillin +/- clavulanate, cefuroxime and clarithromycin, concentration -dependent. As compared to ciprofloxacin, development of resistance wa s less pronounced. The spontaneous mutation frequency towards BAY 12-8 039 resistance was 2.8 x 10(-8) in Escherichia coli, 7.06 x 10-8 in S. aureus and <1.4 x 10(-9) in S. pneumoniae.