In vitro activities of LB20304, a new fluoroquinolone

The in 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-foId more potent activity than ciprofloxacin against gram-positive bacteria. LB20304 inhibited 90% of the isolates of methicillin-susceptible Staphylococcus aureus (MSSA) at a concentration of 0.016 mu g/ml (MIC(90)). MIC(90) values of LB20304 against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus epidermidis (MSSE), methicillin-resistant S. epidermidis (MRSE) and Streptococcus pneumoniae were 2 mu g/ ml, 0.016 mu g/ml, 0.5 mu g/ml and 0.031 mu g/ml, respectively. LB20304 was also very active against gram-negative bacteria. Against Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Pseudomonas aeruginosa and Acinetobacter calcoaceticus, MIC(90)s of LB20304 were 0.031 mu g/ml, 0.25 mu g/ml, 2 mu g/ml, 8 mu g/ml and 0.5 mu g/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, beta-lactamase-producing strains and anaerobic strains. The inhibitory effect (IC50) of LB20304 on DNA gyrase from Micrococcus 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.