title: In vitro activity of BAY 12-8039, a new 8-methoxyquinolone.
abstract: BAY 12-8039 is a new 8-methoxyquinolone with antibacterial activity against gram-positive bacteria which is significantly better than those of sparfloxacin or ciprofloxacin. The minimal inhibitory concentrations (MICs) for 90% of methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis were 0.062 and 2 mg/l, respectively. The MIC90s for ciprofloxacin-resistant, methicillin-susceptible and methicillin-resistant S. aureus were 8 mg/l. Against the staphylococcal strains tested sparfloxacin was 2-fold and ciprofloxacin > or = 10-fold less active. MIC90s for Streptococcus pneumoniae, Streptococcus pyogenes and Streptococcus agalactiae were 0.125-0.5 mg/l, irrespective of whether strains with diminished ciprofloxacin susceptibility 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, except for Pseudomonas aeruginosa. Against Bacteroides fragilis, Bacteroides spp. and Clostridium spp. BAY 12-8039 was as active as metronidazole. The bactericidal activity against S. aureus and S. pneumoniae was in contrast to that of the other quinolones tested, penicillin G, amoxicillin+/-clavulanate, cefuroxime and clarithromycin, concentration-dependent. As compared to ciprofloxacin, development of resistance was less pronounced. The spontaneous mutation frequency towards BAY 12-8039 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.
authors.affiliation: Bayer AG, Pharma Research Center, Wuppertal, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Dalhoff
authors.forename: U
authors.initials: U
authors.lastname: Petersen
authors.forename: R
authors.initials: R
authors.lastname: Endermann
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001372:Aza Compounds; D002939:Ciprofloxacin / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D024841:Fluoroquinolones; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D007769:Lactams; D018942:Macrolides; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D000077266:Moxifloxacin; D011804:Quinolines; D015363:Quinolones / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D007769:Lactams; D018942:Macrolides; D011804:Quinolines; D015363:Quinolones; D002939:Ciprofloxacin; C061363:sparfloxacin; D000077266:Moxifloxacin