gemifloxacin and garenoxacin

This study used Monte Carlo simulations to assess the potential for attainment of pharmacodynamic targets with the fluoroquinolones garenoxacin, gemifloxacin, and moxifloxacin against Streptococcus pneumoniae in serum and epithelial lining fluid (ELF) from hospitalized patients with community-acquired pneumonia (CAP).. Data on the free AUC over 24 hours (fAUC(0-24)), a measure of drug exposure, were derived from previously described population pharmacokinetic models for therapeutic doses of the 3 fluoroquinolones. MIC distribution data for S pneumoniae were obtained from the Canadian Respiratory Organism Susceptibility Study. These data were used to produce the ratio of fAUC(0-24) to the MIC(90) (fAUC(0-24)/MIC(90)), a pharmacodynamic predictor of bacterial eradication. Monte Carlo simulations were used to analyze the potential for garenoxacin 400 mg QD, gemifloxacin 320 mg QD, and moxifloxacin 400 mg QD to achieve target fAUC(0-24)/MIC(90) ratios of 30, 40, 100, and 120 against S pneumoniae in serum and ELF from hospitalized patients with CAP. Target ratios of 30 and 40 were used to assess the probability of bacterial eradication, while ratios of 100 and 120 were used to assess the probability of preventing development of resistance.. Monte Carlo simulations indicated that all 3 fluoroquinolones had a high probability (>90%) of attaining target fAUC(0-24)/MIC(90) ratios of 30 and 40 against S pneumoniae in both serum and ELF. Garenoxacin 400 mg QD was associated with a >95% probability of achieving target fAUC(0-24)/MIC(90) ratios of 100 and 120 in both serum and ELF. Both gemifloxacin 320 mg QD and moxifloxacin 400 mg QD were associated with high probabilities of attaining fAUC(0-24)/MIC(90) ratios of 100 and 120 in ELF (>95%); the probability of gemifloxacin and moxifloxacin attaining these targets in serum ranged from 78.3% to 88.0%.. Based on these simulations, garenoxacin 400 mg QD, gemifloxacin 320 mg QD, and moxifloxacin 400 mg QD appeared likely to achieve target serum and ELF concentrations against S pneumoniae in hospitalized patients with CAP, with a low potential to select for resistance.

Topics: Anti-Bacterial Agents; Area Under Curve; Aza Compounds; Community-Acquired Infections; Fluoroquinolones; Gemifloxacin; Humans; Monte Carlo Method; Moxifloxacin; Naphthyridines; Pneumococcal Infections; Quinolines; Respiratory Mucosa

The activities of garenoxacin, gatifloxacin, and gemifloxacin were compared with those of four fluoroquinolones against human mycoplasmas and ureaplasmas, including fluoroquinolone-resistant genetically characterized strains. Garenoxacin exhibited the highest activity, followed by gemifloxacin, moxifloxacin, and gatifloxacin. The minimal bactericidal activities of these three compounds were lower than those of the four fluoroquinolones.

Topics: Anti-Infective Agents; Fluoroquinolones; Gatifloxacin; Gemifloxacin; Humans; Microbial Sensitivity Tests; Mycoplasma; Mycoplasma Infections; Naphthyridines; Quinolones

Intra-abdominal infections are biphasic, synergistic processes with early peritonitis and bacteremia due to aerobes and a later abscess component due to anaerobes. Although Bacteroides fragilis is the most commonly recognized pathogen, other anaerobes, including other members of the B. fragilis-group species, are major components of infection. Anaerobic bacteremia is often associated with an intra-abdominal source. New antimicrobial agents with anaerobic activity are in various stages of development for the therapy of intra-abdominal infections. The in vitro activity and the currently available sparse clinical data are reviewed for a new carbapenem (ertapenem), several fluoroquinolones (trovafloxacin, moxifloxacin, and gemifloxacin), and a desfluoroquinolone (BMS-284756).

Topics: Abdominal Abscess; Anti-Bacterial Agents; Aza Compounds; Bacteremia; Bacteria, Anaerobic; Bacteroides fragilis; Bacteroides Infections; beta-Lactams; Carbapenems; Clinical Trials as Topic; Ertapenem; Fluoroquinolones; Gemifloxacin; Humans; Indoles; Lactams; Moxifloxacin; Naphthyridines; Quinolines; Quinolones