In vitro activity of gemifloxacin (SB-265805, LB20304a) against Legionella pneumophila and its pharmacokinetics in guinea pigs with L. pneumophila pneumonia
Abstract
The activity of gemifloxacin against intracellular Legionella pneumophila and for the treatment of guinea pigs with L. pneumophila pneumonia was studied. Gemifloxacin, azithromycin, and levofloxacin (1 microg/ml) reduced bacterial counts of two L. pneumophila strains grown in guinea pig alveolar macrophages by 2 to 3 log(10) units. Gemifloxacin and levofloxacin had roughly equivalent intracellular activities. In contrast, erythromycin had static activity only. Therapy studies of gemifloxacin, azithromycin, and levofloxacin were performed in guinea pigs with L. pneumophila pneumonia. When gemifloxacin (10 mg/kg) was given by the intraperitoneal (i.p.) route to infected guinea pigs, mean peak levels in plasma were 1.3 microg/ml at 0.5 h and 1.2 microg/ml at 1 h postinjection. The terminal half-life phase of elimination from plasma was 1.3 h, and the area under the concentration-time curve from 0 to 24 h (AUC(0--24)) was 2.1 microg. h/ml. For the same drug dose, mean levels in lungs were 3.4 microg/g at both 0.5 and 1 h, with a half-life of 1.5 h and an AUC(0--24) of 6.0 microg. h/ml. All 15 L. pneumophila-infected guinea pigs treated with gemifloxacin (10 mg/kg/dose given i.p. once daily) for 2 days survived for 9 days after antimicrobial therapy, as did 13 of 14 guinea pigs treated with the same dose of gemifloxacin given for 5 days. All 12 azithromycin-treated animals (15 mg/kg/dose given i.p. once daily for 2 days) survived, as did 11 of 12 animals treated with levofloxacin…
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