In vitro activities of LB20304, a new fluoroquinolone

Thein vitro activity of LB20304 was evaluated against clinical isolates and compared with those of Q-35, ciprofloxacin, sparfloxacin, lomefloxacin and ofloxacin. LB20304 demonstrated 16- to 64-fold more potent activity than ciprofloxacin against gram-positive bacteria. LB20304 inhibited 90% of the isolates of methicillin-susceptibleStaphylococcus aureus (MSSA) at a concentration of 0.016 μg/ml (MIC₉₀). MIC₉₀ values of LB20304 against methicillin-resistantStaphylococcus aureus (MRSA), methicillin-susceptibleStaphylococcus epidermidis (MSSE), methicillin-resistantS. epidermidis (MRSE) andStreptococcus pneumoniae were 2 μg/ml, 0.016 μg/ml, 0.5 μg/ml and 0.031 μg/ml, respectively. LB20304 was also very active against gram-negative bacteria. AgainstEscherichia coli, Klebsiella pneumoniae, Serratia marcescens, Pseudomonas aeruginosa andAcinetobacter calcoaceticus, MIC₉₀S of LB20304 were 0.031 μg/ml, 0.25 μg/ml, 2 μg/ml, 8 μg/ml and 0.5 μg/ml, respectively. Its activity was comparable to that of ciprofloxacin but much better than those of Q-35, sparfloxacin, ofloxacin and lomefloxacin. LB20304 also exhibited the most potent activity among quinolones tested against laboratory standard strains, ofloxacin-resistant strains, β-lactamase-producing strains and anaerobic strains. The inhibitory effect (IC₅₀) of LB20304 on DNA gyrase fromMicrococcus luteus, determined by the supercoiling assay, was 8-fold more potent than that of ciprofloxacin. LB20304 did not induce topoisomerase-associated DNA cleavage even at a concentration of 10 mg/ml, although ciprofloxacin induced DNA cleavage at a concentration of 1 mg/ml.