In vitro activity of CP-99,219, a novel 7-(3-azabicyclo[3.1.0]hexyl) naphthyridone antimicrobial

• Published in: Diagnostic microbiology and infectious disease Vol. 19; no. 4; pp. 235 - 243
• Main Authors: D. Gootz, Thomas, Brighty, Katherine E., Anderson, Marge R., Schmieder, Brenda J., Haskell, Suzanne L., Sutcliffe, Joyce A., Castaldi, Michael J., McGuirk, Paul R.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.1994; Elsevier
• Subjects: Anti-Infective Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Ciprofloxacin - pharmacology; DNA Topoisomerases, Type II; DNA, Bacterial - drug effects; Fluoroquinolones; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Medical sciences; Microbial Sensitivity Tests; Naphthyridines - pharmacology; Pharmacology. Drug treatments; Quinolones - pharmacology; Performance evaluation; Human; DNA topoisomerase (ATP-hydrolysing); Fluoroquinolone derivative; Drug susceptibility test; Enzyme; Antimicrobial agent; Antibiotic; Isomerases; Minimum inhibitory concentration; Bacteria; Clinical isolate; Comparative study
• ISSN: 0732-8893; 1879-0070
• DOI: 10.1016/0732-8893(94)90037-X

The in vitro activity of CP-99,219 was compared with that of ciprofloxacin and sparfloxacin against 814 clinical bacterial isolates using a microdilution method with brain-heart infusion broth. CP-99,219 was the most potent agent tested against methicillin-resistant, ciprofloxacin-susceptible staphylocci (minimum inhibitory concentration [MIC] 90 ⩽ 0.25 μg/ml). CP-99,219 was 32-fold and fourfold more potent than ciprofloxacin and sparfloxacin, respectively, against Streptococcus pneumoniae, including strains resistant to penicillin G and erythromycin (MIC 90 ⩽ 0.25 μg/ml). CP-99,219 was also the most potent agent tested against S. pyogenes and Enterococcus faecalis (MIC 90 ⩽ 0.5 μg/ml). The activity 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 ⩽ 0.5 μg/ml). Serratia marcescens, Morganella morganii, and Pseudomonas aeruginosa were less susceptible, with MIC 90 values to CP-99,219 of 4, 2, and 2 μg/ml, respectively. The MIC 90 for Bacteroides fragilis was 0.39 μg/ml for CP-99,219 compared with 12.5 μg/ml for ciprofloxacin. CP-99,219 was highly bactericidal at 1 × to 4 × MIC against both Gram-positive and Gram-negative organisms; its activity was similar in nutrient, trypticase soy, and cation-supplemented Mueller-Hinton broths. The spectrum and potency observed with CP-99,219 warrant further testing with this novel quinolone.