title: In vitro activities of fleroxacin against clinical isolates of Legionella spp., its pharmacokinetics in guinea pigs, and use to treat guinea pigs with L. pneumophila pneumonia.
abstract: The activities of fleroxacin against 22 clinical Legionella isolates were determined by agar and broth microdilution susceptibility testing. The fleroxacin MIC required to inhibit 90% of strains tested on buffered charcoal yeast extract agar medium supplemented with 0.1% alpha-ketoglutarate was 0.64 micrograms/ml and was 0.04 microgram/ml when testing was done with buffered yeast extract broth supplemented with 0.1% alpha-ketoglutarate. Fleroxacin (0.25 microgram/ml) reduced the bacterial counts of two L. pneumophila strains grown in guinea pig alveolar macrophages by 1 log10 CFU/ml, but regrowth occurred over a 3-day period; fleroxacin was significantly more active than erythromycin in this assay. Single-dose (10 mg/kg of body weight given intraperitoneally) pharmacokinetic studies performed in guinea pigs with L. pneumophila pneumonia revealed peak levels in plasma and lungs to be 3.3 micrograms/ml and 3.5 micrograms/g, respectively, at 0.5 h and 0.8 microgram/ml and 0.8 microgram/g, respectively, at 1 h. The half-life of the terminal phase of elimination from plasma and lung was approximately 2 h. All 17 infected guinea pigs treated with fleroxacin (10 mg/kg/day) for 2 days survived for 14 days post-antimicrobial therapy, as did all 16 guinea pigs treated with the same dose of fleroxacin for 5 days. Only 1 of 16 animals treated with saline survived. The animals treated with fleroxacin for 2 days lost more weight and had higher temperatures than those treated with the antibiotic for 5 days. Fleroxacin is effective against L. pneumophila in vitro and in a guinea pig model of Legionnaires' disease. Fleroxacin should be evaluated as a treatment for human Legionnaires' disease.
authors: Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia 19104-4283.
authors: P H
authors: PH
authors: Edelstein
authors: M A
authors: MA
authors: Edelstein
authors: B
authors: B
authors: Holzknecht
mesh_terms: D000818:Animals; D016576:Fleroxacin / Q000493:pharmacokinetics / Q000494:pharmacology*; D006168:Guinea Pigs; D016952:Legionella pneumophila / Q000187:drug effects*; D007877:Legionnaires' Disease / Q000188:drug therapy* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000382:microbiology; D008297:Male; D008826:Microbial Sensitivity Tests; D011014:Pneumonia / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology
chemical_list: D016576:Fleroxacin