In vitro and in vivo activities of QA-241, a new tricyclic quinolone derivative.
The in vitro susceptibilities of 1,310 clinical isolates to QA-241, a novel tricyclic quinolone, were evaluated in comparison with susceptibilities to norfloxacin, ofloxacin, enoxacin, and ciprofloxacin. The MICs of QA-241 for 90% of staphylococci, Enterococcus faecalis isolates, and streptococcal species ranged from 1.56 to 6.25 micrograms/ml, and the activity of QA-241 was similar to those of norfloxacin and enoxacin but two to four times less potent than those of ofloxacin and ciprofloxacin. At the concentration of less than or equal to 1.56 micrograms/ml, QA-241 inhibited 90% of Haemophilus influenzae, Bordetella pertussis, Neisseria gonorrhoeae, and gram-negative enteric bacteria except for Serratia marcescens and Citrobacter freundii. QA-241 was moderately active (MIC for 90% of strains tested, 6.25 to 12.5 micrograms/ml) against S. marcescens, Pseudomonas aeruginosa, Xanthomonas maltophilia, and Bacteroides fragilis. The antibacterial activity of QA-241 was roughly comparable to that of enoxacin but two to four times less potent than that of ofloxacin. In systemic infections in mice with gram-positive cocci and gram-negative rods, the efficacy of QA-241 was generally greater than that of norfloxacin and similar to those of ofloxacin and ciprofloxacin. In urinary tract infections in mice with Escherichia coli or Pseudomonas aeruginosa, QA-241 was as active as ofloxacin and more active than norfloxacin but less active than ciprofloxacin. In pulmonary infections in mice with Klebsiella pneumoniae, the effectiveness of QA-241 was similar to that of ofloxacin.
Asahara
M
M
Department of Microbiology, Toho University School of Medicine, Tokyo, Japan.
Tsuji
A
A
Goto
S
S
Masuda
K
K
Kiuchi
A
A
D042462:4-Quinolones; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics; D002412:Cations / Q000494:pharmacology; D003470:Culture Media; D006863:Hydrogen-Ion Concentration; D007710:Klebsiella Infections / Q000188:drug therapy / Q000382:microbiology; D007711:Klebsiella pneumoniae; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011807:Quinolizines; D013997:Time Factors; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000382:microbiology
D042462:4-Quinolones; D000890:Anti-Infective Agents; D002412:Cations; D003470:Culture Media; D011807:Quinolizines; C061232:QA 241