title: Antimicrobial activity of DU-6859, a new potent fluoroquinolone, against clinical isolates.
abstract: DU-6859, (-)-7-[(7S)-amino-5-azaspiro(2,4)heptan-5-yl]-8-chloro-6- fluoro-1-[(1R,2R)-cis-2-fluoro-1-cyclopropyl]-1,4-dihydro-4-oxoquinol one-3- carboxylic acid, is a new fluoroquinolone with antibacterial activity which is significantly better than those of currently available quinolones. The MICs for 90% of methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis clinical isolates (MIC90s) were 0.1, 3.13, 0.1, and 0.39 microgram/ml, respectively. MIC50s of DU-6859 against quinolone-resistant, methicillin-resistant S. aureus were 8-, 32-, 64-, and 128-fold lower than those of tosufloxacin and sparfloxacin, ofloxacin and fleroxacin, ciprofloxacin, and lomefloxacin, respectively. DU-6859 inhibited the growth of all strains of Streptococcus pneumoniae and Streptococcus pyogenes at 0.1 and 0.2 microgram/ml, respectively, and was more active against enterococci than the other quinolones tested. Although the activity of DU-6859 against Pseudomonas aeruginosa was roughly comparable to that of ciprofloxacin at the MIC50 level, it was fourfold more active than ciprofloxacin at the MIC90 level. DU-6859 was also more active against other glucose-nonfermenting bacteria, Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae, than the other drugs tested. Strains of Bacteroides fragilis and Peptostreptococcus spp. were susceptible to DU-6859; MIC90s were 0.39 and 0.2 microgram/ml, respectively. DU-6859 generally showed activities twofold or greater than those of ciprofloxacin and the other drugs against almost all members of the family Enterobacteriaceae. The action of DU-6859 against the clinical isolates was bactericidal at concentrations near the MICs. DU-6859 activity was not affected by different media, pH, inoculum size, or human serum but was decreased in human urine.
authors.affiliation: Exploratory Research Laboratories I, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Hoshino
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: I
authors.initials: I
authors.lastname: Hayakawa
authors.forename: Y
authors.initials: Y
authors.lastname: Osada
mesh_terms: D000890:Anti-Infective Agents / Q000097:blood / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D024841:Fluoroquinolones; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D015363:Quinolones / Q000097:blood / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C076246:sitafloxacin