title: Therapeutic effect of oral levofloxacin, ciprofloxacin, and ampicillin on experimental murine pneumonia caused by penicillin intermediate Streptococcus pneumoniae for which the minimum inhibitory concentrations of the quinolones are similar.
abstract: The therapeutic efficacy of oral treatment with levofloxacin, ciprofloxacin, and ampicillin on an experimental pneumonia caused by the penicillin-intermediate Streptococcus pneumoniae for which the minimum inhibitory concentrations (MICs) of the quinolones are similar was assessed in immunocompetent CBA/J mice. Levofloxacin exhibited a dose-dependent therapeutic effect, and achieved complete eradication of S. pneumoniae from the lungs at 120 mg/kg/day, whereas ciprofloxacin and ampicillin were hardly effective at all. A pharmacokinetic study in infected mice revealed good oral absorption and lung tissue penetration of levofloxacin (peak lung concentration: 5.95 microg/g of lung), low oral absorption of ciprofloxacin in spite of a good penetration into lung tissue (1.10 microg/g of lung), and low lung tissue penetration of ampicillin despite rather good oral absorption (1.71 microg/g of lung). In an in vitro time-kill study that simulated the peak concentration of drugs in the lungs of infected animals, the killing activity of levofloxacin was found to be greater than that of ciprofloxacin and ampicillin. These data suggest that the therapeutic efficacy of levofloxacin in this model is attributable to both its potent bactericidal activity and excellent pharmacokinetic profile.
authors.affiliation: New Product Research Laboratories 1, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ishida
authors.forename: Y
authors.initials: Y
authors.lastname: Kurosaka
authors.forename: Y
authors.initials: Y
authors.lastname: Murakami
authors.forename: T
authors.initials: T
authors.lastname: Otani
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000667:Ampicillin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D064704:Levofloxacin; D008168:Lung / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D010406:Penicillins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy*; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D010406:Penicillins; D002939:Ciprofloxacin; D064704:Levofloxacin; D000667:Ampicillin; D015242:Ofloxacin