Comparative in vitro activity of a new fluorinated 4-quinolone, QA-241

Abstract

The in vitro activity of a new quinolone, QA-241, 9-fluoro-6,7-dihydro-5-methyl-8(4-methyl-1-piperazinyl) -1,7-dioxo-1 H,5H-benzo[ii]quinolizine-2-carboxylic hydrochloride, was compared with those of ciprofloxacin, ofloxacin, ceftazidime, imipenem, and gentamicin. QA-241 inhibited 90% of isolates of Enterobacteriaceae at a concentration of ⩽2 μg/ml. It was two-fold and four- to 16-fold less active than ofloxacin and ciprofloxacin, respectively. QA-241 was less active against Pseudomonas aeruginosa and other Pseudomonas species than ciprofloxacin. Most Haemophilus influenzae and Neisseria gonorrhoeae isolates were inhibited at concentrations of ⩽0.03 μg/ml. The MIC for 90% of Staphylococcus aureus isolates, including methicillin-resistant S. aureus, was 1 μg/ml, as was that for S. epidermidis. For streptococci, including Streptococcus faecalis, the MIC 90 was 4 μg/ml. QA-241 had minimal activity against anaerobic species. The frequency of spontaneous resistance was less than 10 −9 for members of the Enterobacteriaceae. However, resistant strains could be isolated by repeated subculture. Similar to other quinolones, its activity was less at an acid pH and in the presence of high Mg 2+ concentrations. QA-241 showed a good postantibiotic suppressive effect on Escherichia coli.