In vivo activity of gemifloxacin, moxifloxacin and levofloxacin against pneumococci with gyrA and parC point mutations in a sepsis mouse model measured with the all or nothing mortality end-point

Int J Antimicrob Agents. 2005 Feb;25(2):163-7. doi: 10.1016/j.ijantimicag.2004.08.017.

Abstract

A dose-decreasing immunocompetent sepsis mouse model was used to evaluate the in vivo effect of levofloxacin, moxifloxacin and gemifloxacin, using a ciprofloxacin/levofloxacin susceptible serotype 6B strain (ciprofloxacin MIC: 1 mg/l) and two resistant serotype 14 and 19F strains with gyrA and parC point mutations (ciprofloxacin MICs of 32 and 64 mg/l, respectively). Significant higher in vivo activity was found for moxifloxacin and gemifloxacin than for levofloxacin against strains 1 and 2, and for gemifloxacin versus moxifloxacin or levofloxacin against strain 3. Gemifloxacin treatment resulted in 100% survival against strains 1 and 2(AUC0-24 h/MIC of 30 and 62) but against strain 3, survival was 60-80% (AUC0-24 h/MIC of 93). Similar AUC0-24 h/MIC values produced different therapeutic results suggesting that in vitro parameters other than the MIC could influence efficacy predictions based on in vitro susceptibility tests (MICs) or pharmacodynamic parameters (AUC0-24 h/MIC).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / pharmacology
  • Anti-Infective Agents / therapeutic use*
  • Aza Compounds / pharmacology
  • Aza Compounds / therapeutic use
  • Ciprofloxacin / pharmacology
  • DNA Gyrase / genetics*
  • DNA Topoisomerase IV / genetics*
  • Disease Models, Animal
  • Drug Resistance, Bacterial
  • Female
  • Fluoroquinolones / pharmacology
  • Fluoroquinolones / therapeutic use*
  • Gemifloxacin
  • Levofloxacin
  • Mice
  • Microbial Sensitivity Tests
  • Moxifloxacin
  • Naphthyridines / pharmacology
  • Naphthyridines / therapeutic use
  • Ofloxacin / pharmacology
  • Ofloxacin / therapeutic use
  • Pneumococcal Infections / drug therapy
  • Pneumococcal Infections / microbiology
  • Pneumococcal Infections / mortality
  • Point Mutation
  • Quinolines / pharmacology
  • Quinolines / therapeutic use
  • Sepsis / drug therapy*
  • Sepsis / microbiology
  • Sepsis / mortality
  • Streptococcus pneumoniae / drug effects*
  • Streptococcus pneumoniae / enzymology
  • Streptococcus pneumoniae / genetics
  • Treatment Outcome

Substances

  • Anti-Infective Agents
  • Aza Compounds
  • Fluoroquinolones
  • Naphthyridines
  • Quinolines
  • Ciprofloxacin
  • Levofloxacin
  • Ofloxacin
  • DNA Topoisomerase IV
  • DNA Gyrase
  • Gemifloxacin
  • Moxifloxacin