In vitro activity of gemifloxacin against a broad range of recent clinicalisolates from the USA

The antibacterial potencies of gemifloxacin (SB-265805) and 13 comparator c ompounds were determined by broth microdilution against a panel of 645 Gram -positive and 995 Gram-negative organisms collected from various USA sites. Time-kill studies were performed and postantibiotic effect (PAE) was deter mined for several organisms using trovafloxacin and ciprofloxacin as compar ator compounds. Based on MIC(90)s, gemifloxacin was the most potent compoun d tested against Gram-positive isolates: Streptococcus pneumoniae (MIC90 0. 016 mg/L), Streptococcus agalactiae (0.03 mg/L), Streptococcus pyogenes (0. 03 mg/L), viridans streptococci (0.12 mg/L), methicillin-susceptible Staphy lococcus aureus (0.03 mg/L), Staphylococcus epidermidis (2 mg/L), Staphyloc occus saprophyticus (0.016 mg/L) and Enterococcus faecalis (2 mg/L). Agains t Gram-negative isolates, the potency of gemifloxacin was equal to that of levofloxacin and ciprofloxacin and generally better than that of ofloxacin, grepafloxacin, trovafloxacin and nalidixic acid. MIC(90)s for gemifloxacin were: Haemophilus influenzae (less than or equal to 0.008 mg/L), Moraxella catarrhalis (0.008 mg/L), Escherichia coli(0.016 mg/L), Klebsiella pneumon iae (0.25 mg/L), Klebsiella oxytoca (0.25 mg/L), Enterobacter cloacae (1 mg /L), Enterobacter aerogenes (0.25 mg/L), Proteus spp. (4 mg/L), Serratia sp p. (1 mg/L), Citrobacter freundii (2 mg/L), Morganella morganii (0.12 mg/L) , Pseudomonas aeruginosa (8 mg/L), Stenotrophomonas maltophilia (4 mg/L) an d Acinetobacter spp. (32 mg/L). Gemifloxacin was bactericidal for all organ isms studied at 2 and 4 x MIG. The PAE for most strains was in the range 0. 7-2.5 h at 2 and 4 x MIG, although longer PAEs were observed with H. influe nzas, P. aeruginosa and Proteus vulgaris (>6 h at 4 x MIC) and shorter PAEs with E. faecalis(0.1-0.6 h) and K. pneumoniae(0.1-0.2 h). In conclusion, g emifloxacin is a novel quinolone with a broad spectrum of antimicrobial act ivity. It has substantially improved potency against Gram-positive organism s, especially streptococci, for which gemifloxacin is generally at least ei ght- to 16-fold more potent than other quinolones tested. It retains the go od Gram-negative activity seen with ciprofloxacin and levofloxacin and show s good bactericidal activity and prolonged PAEs.