Comparative Killing Kinetics of the Novel des-fluoro(6) Quinolone BMS-284756, Fluoroquinolones, Vancomycin and Beta-Lactams

Int J Antimicrob Agents. 2001 Jul;18(1):43-8. doi: 10.1016/s0924-8579(01)00343-0.

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.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Infective Agents / pharmacology*
  • Bacteria / drug effects*
  • Enterobacteriaceae / drug effects
  • Enterococcus faecalis / drug effects
  • Fluoroquinolones*
  • Indoles*
  • Kinetics
  • Levofloxacin
  • Microbial Sensitivity Tests
  • Naphthyridines / pharmacology
  • Ofloxacin / pharmacology
  • Quinolones*
  • Staphylococcus aureus / drug effects
  • Streptococcus / drug effects
  • Vancomycin / pharmacology*
  • beta-Lactams

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Fluoroquinolones
  • Indoles
  • Naphthyridines
  • Quinolones
  • beta-Lactams
  • Levofloxacin
  • Vancomycin
  • trovafloxacin
  • Ofloxacin
  • garenoxacin