Activity of non-fluorinated quinolones (NFQs) against quinolone-resistant Escherichia coli and Streptococcus pneumoniae

J Antimicrob Chemother. 2001 Jul;48(1):29-36. doi: 10.1093/jac/48.1.29.

Abstract

The newly developed 8-methoxy, non-fluorinated quinolones (NFQs) were studied to elucidate their enzyme inhibitory activity against wild-type and mutant GyrA (Ser-83-->Trp) forms of Escherichia coli DNA gyrase. Using a DNA supercoiling inhibition assay, the NFQs were found to inhibit 50% (IC50) of the E. coli DNA gyrase activity in the 1.6-3.2 mg/L concentration range and were comparable to ciprofloxacin. However, against the GyrA (Ser-83-->Trp) mutant, the NFQs were approximately 16-fold more potent than ciprofloxacin. Antibacterial potency of the NFQs was investigated using clinical isolates of E. coli and penicillin-resistant Streptococcus pneumoniae (PRSP), including strains with reduced susceptibility to quinolones. Against 20 uncharacterized clinical isolates of E. coli, the MIC90s of the NFQs were in the 0.125-0.25 mg/L range while those of ciprofloxacin, trovafloxacin, gatifloxacin and clinafloxacin were in the 0.016-0.125 mg/L range. Against clinical isolates with characterized mutations in gyrA and parC, PGE9262932, an NFQ, was two- to eight-fold more potent than ciprofloxacin. Against 23 clinical isolates of PRSP, the NFQs (MIC90 0.031-0.125 mg/L) were more potent than ciprofloxacin, trovafloxacin, and gatifloxacin (MIC90 0.25-2.0 mg/L), and at least as potent as clinafloxacin (MIC90 0.125 mg/L). Against S. pneumoniae strains with gyrA and parC mutations, the NFQs (MIC 0.125-1.0 mg/L) were more potent than ciprofloxacin, trovafloxacin and gatifloxacin (MIC 4-32 mg/L), and comparable to clinafloxacin (MIC 0.5-1 mg/L).

MeSH terms

  • Anti-Infective Agents / pharmacology*
  • DNA Gyrase
  • DNA Topoisomerase IV
  • DNA Topoisomerases, Type II / genetics
  • Drug Resistance, Microbial
  • Escherichia coli / drug effects*
  • Fluoroquinolones
  • Microbial Sensitivity Tests
  • Streptococcus pneumoniae / drug effects*
  • Topoisomerase II Inhibitors

Substances

  • Anti-Infective Agents
  • Fluoroquinolones
  • Topoisomerase II Inhibitors
  • DNA Topoisomerase IV
  • DNA Gyrase
  • DNA Topoisomerases, Type II