In vitro antimicrobial activity, penetration into sputum and therapeutic efficacy of fleroxacin in respiratory infections

We measured the in vitro antimicrobial activity, and serum and sputum concentrations of fleroxacin, a new quinolone agent for oral use, and evaluated its therapeutic efficacy in respiratory infections. The minimum inhibitory concentrations (MICs) of fleroxacin and ofloxacin (OFLX) against 20 strains each of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa were determined by a microbroth dilution method using the Dynatech MIC-2000 system. As shown by the MICs, fleroxacin was somewhat less active than OFLX against all these species. The concentrations of fleroxacin in the serum of three patients with respiratory infections were highest at 2h after oral administration of 300mg (7.41, 2.82 and 3.93 μg/ml). The penetration rate of fleroxacin from serum at 2 h after oral administration into the sputum collected during 2h thereafter was 91%, 66% and 52% in these 3 patients. Thereafter, the concentrations of fleroxacin in their serum and sputum decreased gradually: at 24h after administration, the concentrations of fleroxacin in serum were 1.66, 0.72 and 0.53 μ;g/ml and those in sputum were 1.63, 0.53 and 0.23 μg/ml. A daily dose of 200-300mg of fleroxacin was given orally for 5-14 days (mean: 7.8 days) to 10 patients: 4 with acute bronchitis, 1 with infection supervening on bronchiectasis and 5 with acute pneumonia. The clinical efficacy was assessed as excellent in 1, good in 6, fair in 1 and poor in 2. Six strains were identified as causative organisms, five of which were eradicated by fleroxacin. Mild epigastric pain and elevation of eosinophils were each observed in one patient. From the above results, we conclude that fleroxacin is one of the most useful quinolone agents for oral use in the treatment of respiratory infections.