In vitro activity of gemifloxacin (SB-265805, LB20304a) against Legionellapneumophila and its pharmacokinetics in guinea pigs with L-pneumophila pneumonia

The activity of gemifloxacin against intracellular Legionella pneumophila a nd for the treatment of guinea pigs with L, pneumophila pneumonia was studi ed. Gemifloxacin, azithromycin, and levofloxacin (1 mug/ml) reduced bacteri al counts of two L, pneumophila strains grown in guinea pig alveolar macrop hages by 2 to 3 log(10) units. Gemifloxacin and levofloxacin had roughly eq uivalent intracellular activities, In contrast, erythromycin had static act ivity only. Therapy studies of gemifloxacin, azithromycin, and levofloxacin were performed in guinea pigs with L, pneumophila pneumonia, When gemiflox acin (10 mg/kg) was given by the intraperitoneal (i,p,) route to infected g uinea pigs, mean peak levels in plasma were 1.3 mug/ml at 0.5 h and 1.2 mug /ml at 1 h postinjection, The terminal half-life phase of elimination from plasma,vas 1.3 h, and the area under the concentration-time curve from 0 to 24 h (AUC(0-24)) was 2.1 mug . h/ml, For the same drug dose, mean levels i n lungs were 3.4 mug/g at both 0.5 and 1 h, with a half-life of 1.5 h and a n AUG0-24 of 6.0 mug . h/ml, All 15 L. pneumophila-infected guinea pigs tre ated with gemifloxacin (10 mg/kg/dose given i,p, once daily) for 2 days sur vived for 9 days after antimicrobial therapy, as did 13 of 14 guinea pigs t reated with the same dose of gemifloxacin given for 5 days. All 12 azithrom ycin-treated animals (15 mg/kg/dose given i,p, once daily for 2 days) survi ved, as did 11 of 12 animals treated with levofloxacin (10 mg/kg/dose given i,p, once daily for 5 days). None of 12 animals treated with saline surviv ed, Gemifloxacin is effective against L, pneumophila in infected macrophage s and in a guinea pig model of Legionnaires' disease, even with an abbrevia ted course of therapy. These data support studies of the clinical effective ness of gemifloxacin for the treatment of Legionnaires' disease.