INVITRO ACTIVITIES OF FLEROXACIN AGAINST CLINICAL ISOLATES OF LEGIONELLA SPP, ITS PHARMACOKINETICS IN GUINEA-PIGS, AND USE TO TREAT GUINEA-PIGS WITH L-PNEUMOPHILA PNEUMONIA

ne 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 mug/ml and was 0.04 mug/ml when testing was done with buffered yeast extract broth supplemented with 0.1% alpha-ketoglutarate. Fleroxacin (0.25 mug/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 mug/ml and 3.5 mug/g, respectively, at 0.5 h and 0.8 mug/ml and 0.8 mug/g, respectively, at 1 h. The half-life of the terminal phase of elimination from plasma and lung was almost-equal-to 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.