title: In vitro antibacterial activities of new fluoroquinolones against clinical isolates of haemophilus influenzae with ciprofloxacin-resistance-associated alterations in GyrA and ParC.
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.
authors.affiliation: Department of Microbiology, Toho University School of Medicine, Tokyo, Japan. satoshi-yoshizum@mtc.biglobe.ne.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshizumi
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Eiichi
authors.initials: E
authors.lastname: Okezaki
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ishii
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology*; D027081:DNA Gyrase / Q000187:drug effects / Q000235:genetics*; D027101:DNA Topoisomerase IV / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics*; D024841:Fluoroquinolones / Q000494:pharmacology*; D005798:Genes, Bacterial / Q000235:genetics; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D002939:Ciprofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase