Abstract
The in vitro and in vivo antibacterial activities of grepafloxacin (GPFX), a new synthetic antimicrobial agent, were compared with those of norfloxacin (NFLX), ofloxacin (OFLX), enoxacin (ENX) and ciprofloxacin (CPFX). GPFX showed a broad spectrum of antibacterial activity against gram-positive and gram-negative and aerobic and anaerobic bacteria. GPFX was superior to reference compounds in activity against all gram-positive clinical isolates, including Staphylococcus aureus and Streptococcus pneumoniae. The antibacterial activity of GPFX against Escherichia coli, Citrobacter diversus, Klebsiella pneumoniae and Enterobacter aerogenes was similar to that of CPFX and superior to those of NFLX, ENX and OFLX. The activity of GPFX against Klebsiella oxytoca, Enterobacter cloacae, Serratia marcescens, Pseudomonas aeruginosa and Pseudomonas putida was slightly less than that of CPFX but more active than those other reference drugs. The activity was similar to that of ENX against Citrobacter freundii, Proteus vulgaris, Proteus mirabilis, Providencia rettgeri and Morganella morganii. GPFX was superior to the reference compounds in activity against Haemophilus influenzae, Xanthomonas maltophilia, Acinetobacter calcoaceticus, Moraxella (Branhamella) catarrhalis and Bacteroides fragilis. Neither the medium, variation in medium pH, inoculum size, nor the addition of cations or horse serum had any major effect on its activity. But the activity of GPFX was slightly reduced in the acidic condition and of a high concentration of cations. GPFX acted bactericidally over the MIC, and differences were very small between the MIC and MBC.
Frequencies of mutants resistant to GPFX were low. GPFX strongly inhibited the supercoiling activity of DNA gyrase purified from E. coli K-12. But inhibition of the relaxing activity of topoisomerase II from calf thymus was very low. GPFX produced excellent postantibiotic effects (PAE) against S. aureus and E. coli, and those effects were 2 and 1.6 hours, respectively. The therapeutic effect of these quinolones was evaluated against systemic infections in mice. GPFX was the most active against all the gram-positive bacterial infections. In gram-negative bacterial infections, GPFX was similar in activity to CPFX against E. coli and P. aeruginosa infections and was most active against H. influenzae infection. These results indicate that GPFX may be useful for various kinds of infections in humans.
