IN-VITRO ACTIVITY OF CP-99,219, A NOVEL 7-(3-AZABICYCLO[3.1.0]HEXYL) NAPHTHYRIDONE ANTIMICROBIAL

The in vitro activity of CP-99,219 was compared with that of ciproflox acin and sparfloxacin against 814 clinical bacterial isolates using a microdilution method with brain-heart infusion broth. CP-99,219 was th e most potent agent tested against methicillin-resistant, ciprofloxaci n-susceptible staphylocci (minimum inhibitory concentration [MIC](90) less than or equal to 0.25 mu g/ml). CP-99,219 was 32-fold and fourfol d more potent than ciprofloxacin and sparfloxacin, respectively, again st Streptococcus pneumoniae, including strains resistant to penicillin G and erythromycin (MIC(90) less than or equal to 0.25 mu g/ml). CP-9 9,219 was also the most potent agent tested against S. pyogenes and En terococcus faecalis (MIC(90) less than or equal to 0.5 mu g/ml). The a ctivity of CP-99,219 against Enterobacteriaceae was comparable to that of sparfloxacin, with 90% of Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Citrobacter freundii, C . diversus, Helicobacter pylori, and K. oxytoca being inhibited by les s than or equal to 0.5 mu g/ml, Serratia marcescens, Morganella morgan ii, and Pseudomonas aeruginosa were less susceptible, with MIC(90) val ues to CP-99,219 of 4, 2, and 2 mu g/ml, respectively. The MIC(90) for Bacteroides fragilis was 0.39 mu g/ml for CP-99,219 compared with 12. 5 mu g/ml for ciprofloxacin. CP-99,219 was highly bactericidal at 1 x to 4 x MIC against both Gram-positive and Gram-negative organisms, its activity was similar in nutrient, trypticase soy, and cation-suppleme nted Mueller-Hinton broths. The spectrum and potency observed with CP- 99,219 warrant further testing with this novel quinolone.