IN-VITRO ACTIVITY OF LEVOFLOXACIN AGAINST CLINICAL ISOLATES OF LEGIONELLA SPP, ITS PHARMACOKINETICS IN GUINEA-PIGS, AND USE IN EXPERIMENTALLEGIONELLA-PNEUMOPHILA PNEUMONIA

The activities of levofloxacin and ofloxacin against 22 clinical legio nella isolates was determined by microbroth dilution susceptibility te sting. Growth inhibition of two Legionella pneumophila strains grown i n guinea pig alveolar macrophages by levofloxacin, ofloxacin, or eryth romycin was also determined. The drug concentrations required to inhib it 90% of strains tested was 0.032 mg/L for levofloxacin or ofloxacin, and was 0.016 mg/L for ciprofloxacin. BYE alpha broth significantly i nhibited the activities of all three drugs tested, as judged by the su sceptibility of control Escherichia coli strains. Levofloxacin (0.25 m g/L) reduced bacterial counts of two L. pneumophila strains grown in g uinea pig alveolar macrophages by 1 log(10), but regrowth occurred ove r a 3 day period; levofloxacin (1 mg/L) reduced bacterial counts by 2- 3 log(10) cfu/mL. Levofloxacin was significantly more active than eryt hromycin. and as active as ofloxacin or ciprofloxacin in this assay. P harmacokinetic and therapy studies of levofloxacin and ofloxacin were performed in guinea pigs with L. pneumophila pneumonia. For the pharma cokinetic study, levofloxacin was given (10 mg/kg) by the intraperiton eal route to infected guinea pigs; mean peak plasma and lung concentra tions were 3.4 mg/L and 1.4 mu g/g, respectively, at 0.5 h and 2.6 mg/ L and 0.6 mu g/g at 1 h. The terminal half-life phase of elimination f rom plasma and lung was c. 1 h. All lj infected guinea pigs treated wi th levofloxacin (10 mg/kg/day given ip once daily) for 5 days survived for 9 days after antimicrobial therapy, as did all 14 guinea pigs tre ated with the same dose of ofloxacin. None of 13 animals treated with saline survived. Levofloxacin is effective against L. pneumophila in v itro and in a guinea pig model of legionnaire's disease. Levofloxacin should be evaluated as a treatment of human legionnaires' disease.