In vitro antibacterial activities of new fluoroquinolones against clinical isolates of haemophilus influenzae with ciprofloxacin-resistance-associated alterations in GyrA and ParC.
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.
Yoshizumi
Satoshi
S
Department of Microbiology, Toho University School of Medicine, Tokyo, Japan. satoshi-yoshizum@mtc.biglobe.ne.jp
Takahashi
Yoshie
Y
Watanabe
Yoshinari
Y
Okezaki
Eiichi
E
Ishii
Yoshikazu
Y
Tateda
Kazuhiro
K
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
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D002939:Ciprofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase