Comparative in vitro activity of a new quinolone, AM-1091

Abstract

The in vitro activity of a new quinolone, AM-1091 [7-(3-amino-1-pyrrolidinyl)-8-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid hydrochloride], was compared with those of ciprofloxacin, ofloxacin, beta-lactams, and gentamicin. AM-1091 inhibited 90% of the isolates of the family Enterobacteriaceae at .ltoreq. 0.12 .mu.g/ml. For many species AM-1091 was 2-fold more active than ciprofloxacin and 2- to 32-fold more active than ofloxacin. It inhibited Enterobacter, Citrobacter and Klebsiella species resistant to ceftazidime and gentamicin. Ninety percent of Pseudomonas aeruginosa isolates were inhibited by 0.5 .mu.g/ml, so for this species AM-1091 was twofold less active than ciprofloxacin. AM-1091 was twofold less active than ciprofloxacin. AM-1091 was more active against Pseudomonas cepacia and Xanthomonas maltophilia, inhibiting isolates resistant to imipenem and gentamicin. Most Haemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis, and Branhamella catarrhalis isolates were inhibited by .gtoreq. 0.06 .mu.g/ml. The MICs for 90% of Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis isolates were 0.06, 0.06 and 2 .mu.g/ml, respectively. AM-1091 inhibited hemolytic streptococci and Streptococcus pneumoniae at 0.25 .mu.g/ml and was more active than ciprofloxacin or ofloxacin against gram-positive species. AM-1091 inhibited 90% of the Bacteroides species at 0.5 .mu.g/ml. The frequency of spontaneous resistance was < 10-10 for most organisms, but resistant strains could be selected by repeated subculturing. Although AM-1091 had lower in vitro activity at pH 5.5 and in the presence of high concentrations of Mg2+, it still inhibited most organisms at .ltoreq. 0.5 .mu.g/ml under these conditions. AM-1091 rapidly killed Escherichia coli and P. aeruginosa and had a prolonged postantibiotic suppressive effect on these bacteria.