In vitro antimicrobial activity and penetration rate into sputum of gatifloxacin, a novel 6-fluoro-8-methoxy quinolone, and its therapeutic efficacy in respiratory infections.

The in vitro antimicrobial activity of gatifloxacin against clinical isolates of pathogenic bacteria was evaluated. Minimum inhibitory concentrations of gatifloxacin, ofloxacin, ciprofloxacin, tosufloxacin, sparfloxacin, and rifampicin against 20 strains each of methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa, 18 strains of Enterobacter cloacae, 15 strains each of Streptococcus Pneumoniae and Moraxella catarrhalis, 12 strains of Haemophilus influenzae, 18 strains of Mycobacterium intracellulare, and 22 strains each of Mycobacterium tuberculosis and Mycobacterium avium were determined. The minimum inhibitory concentrations90's of gatifloxacin against the above species were 0.12, 8, <==0.06, 0.5, 2, 2, <==0.06, 0.39, 0.05, 0.013, 2, 0.5, and 4 &mgr;g/ml, respectively. Gatifloxacin was four times as active as ofloxacin against methicillin-susceptible and -resistant Staphylococcus aureus, and as active as ofloxacin against Enterobacteriaceae and Pseudomonas aeruginosa. Gatifloxacin was as active as tosufloxacin and sparfloxacin against Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae. The antimycobacterial activity of gatifloxacin was similar to that of sparfloxacin. Five patients with chronic respiratory infections and one patient with acute pneumonia received 100-400 mg/day of gatifloxacin orally for 5-12 days (mean, 8.17 days). The clinical effects were excellent in one patient and good in five. One strain of Haemophilus influenzae was eradicated and one strain of Pseudomonas aeruginosa persisted after therapy. Adverse reactions were mild and improved after completion of therapy. In one patient with chronic bronchitis, the maximum sputum concentrations 2-4 h after oral administration of 150 mg of gatifloxacin on days 1 and 6 were 0.88 and 1.45 &mgr;g/ml, respectively, and in serum the values were 0.84 and 1.24 &mgr;g/ml, respectively. Thus it was found that gatifloxacin possesses potent activity against respiratory pathogens (including Mycobacteriaceae), and shows good penetration rate into sputum, and that it can be used as the drug of first choice in the treatment of respiratory tract infections.