title: Comparative killing kinetics of the novel des-fluoro(6) quinolone BMS-284756, fluoroquinolones, vancomycin and beta-lactams.
abstract: The primary bactericidal classes used therapeutically as single agents, are the quinolones and the cell-wall active agents. In this study, their rates of killing were compared. The des-fluoro(6) quinolone BMS-284756 (T-3811ME), fluoroquinolones (trovafloxacin, levofloxacin) and cell wall-active agents (beta-lactams, vancomycin) were evaluated against Enterobacteriaceae, Staphylococcus aureus, streptococci, and Enterococcus faecalis. Time-kill analysis was done at 10x the MIC, using Mueller-Hinton broth (supplemented with 7% lysed horse blood for Streptococcus pneumoniae and the viridans streptococci), or Brain Heart Infusion broth for beta-haemolytic streptococci. Using a 3-log(10) decrease in viable count as an index of bactericidal activity, BMS-284756 and the fluoroquinolones killed Enterobacteriaceae rapidly, requiring < 2 h versus > or =6 h for beta-lactams. The staphylococcal cell counts generally decreased more rapidly with quinolone exposure, compared with those treated with vancomycin or the beta-lactams. The antimicrobial agents killed streptococci and enterococci more slowly, requiring > 6 h to decrease the viable count by 99.9%. In summary, BMS-284756 killing rates are similar to those of recent fluoroquinolones and are bacterial group-dependent. Overall, the quinolones are more rapidly bactericidal than vancomycin and the beta-lactam antibiotics.
authors.affiliation: Department of Microbiology, Bristol-Myers Squibb Company, 5 Research Pathway, PO Box 5100, 06492-7660, Wallingford, CT, USA.
authors.forename: E
authors.initials: E
authors.lastname: Gradelski
authors.forename: L
authors.initials: L
authors.lastname: Valera
authors.forename: B
authors.initials: B
authors.lastname: Kolek
authors.forename: D
authors.initials: D
authors.lastname: Bonner
authors.forename: J
authors.initials: J
authors.lastname: Fung-Tomc
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D004755:Enterobacteriaceae / Q000187:drug effects; D013293:Enterococcus faecalis / Q000187:drug effects; D024841:Fluoroquinolones; D007211:Indoles; D007700:Kinetics; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D015363:Quinolones; D013211:Staphylococcus aureus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects; D014640:Vancomycin / Q000494:pharmacology*; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D007211:Indoles; D009287:Naphthyridines; D015363:Quinolones; D047090:beta-Lactams; D064704:Levofloxacin; D014640:Vancomycin; C080163:trovafloxacin; D015242:Ofloxacin; C419689:garenoxacin