In vitro antibacterial activities of new fluoroquinolones against clinical isolates of haemophilus influenzae with ciprofloxacin-resistance-associated alterations in GyrA and ParC

Chemotherapy. 2004 Dec;50(6):265-75. doi: 10.1159/000082624. Epub 2004 Dec 8.

Abstract

Background: The in vitro antimicrobial activities of new fluoroquinolones were tested against quinolone-resistant Haemophilus influenzae of clinical isolates.

Methods: The nucleotide sequences of the gyrA and parC genes from three ciprofloxacin-resistant strains of Haemophilus influenzae (MIC, 1.56-6.25 microg/ml) were determined. The gyrase was purified from the clinical isolates, and the inhibitory activities of quinolones against the enzyme were tested.

Results: These strains possessed at least one amino acid substitution in each of the GyrA (asparagine at residue 88 (Asp-88) to Tyr, Ser-84 to Leu or Ser-84 to Leu and Asp-88 to Asn) and ParC (Glu-88 to Lys). The antibacterial activity of olamufloxacin against the resistant strains was most potent compared with other quinolones, and the inhibitory activities correlated with quinolone resistance of these strains.

Conclusions: These results warrant the clinical effects of new types of fluoroquinolones, such as olamufloxacin, against respiratory tract and otolaryngology infections caused by ciprofloxacin-resistant H. influenzae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents / pharmacology
  • Ciprofloxacin / pharmacology*
  • DNA Gyrase / drug effects
  • DNA Gyrase / genetics*
  • DNA Topoisomerase IV / genetics*
  • Drug Resistance, Microbial / genetics*
  • Fluoroquinolones / pharmacology*
  • Genes, Bacterial / genetics
  • Haemophilus influenzae / drug effects*
  • Haemophilus influenzae / genetics
  • Haemophilus influenzae / isolation & purification
  • In Vitro Techniques
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Mutation

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Fluoroquinolones
  • Ciprofloxacin
  • DNA Topoisomerase IV
  • DNA Gyrase