Primary levofloxacin resistance and gyrA/B mutations among Helicobacter pylori in Japan

Helicobacter. 2006 Aug;11(4):243-9. doi: 10.1111/j.1523-5378.2006.00415.x.

Abstract

Background: Recent years have witnessed a decrease in the rate of Helicobacter pylori eradication due to antimicrobial resistance, clarithromycin or metronidazole resistance in particular. As one of the alternatives to the standard regimens, levofloxacin-containing therapy has been considered a promising regimen. Nevertheless, there is a little information concerning the prevalence of levofloxacin resistance and this resistance mechanism.

Materials and methods: Levofloxacin susceptibility was examined using E-test in 507 H. pylori strains clinically isolated in Japan from 2001 to 2004. Mutation patterns in the quinolone resistance-determining regions of the gyrA and gyrB genes were evaluated, performing direct sequencing of 68 levofloxacin-resistant and 50 susceptible strains.

Results: Primary levofloxacin resistance was found in 76 (15.0%) strains. Fifty-seven (83.8%) of 68 levofloxacin-resistant strains analyzed had point mutations in gyrA at Asn-87 or Asp-91, while seven (14.0%) of 50 susceptible strains had gyrA mutations. There was a significant difference in the occurrence of gyrA mutations between levofloxacin-resistant and -susceptible strains (p < .001). In levofloxacin-resistant strains, the occurrence of gyrA mutations at Asn-87 was most common regardless of minimal inhibitory concentration levels, and that of gyrA mutations at Asp-91 tended to be associated with low-level resistance. A double gyrA mutation at Asn-87 and Asp-91 might have an additional impact. As for gyrB, three (4.4%) of 68 levofloxacin-resistant strains with no susceptible strains had mutations.

Conclusions: Primary levofloxacin resistance was common in Japan and primarily related to gyrA mutations at Asn-87 and Asp-91.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • DNA Gyrase / genetics*
  • DNA Mutational Analysis
  • DNA, Bacterial / genetics
  • Drug Resistance, Bacterial / genetics*
  • Female
  • Helicobacter Infections / microbiology*
  • Helicobacter pylori / drug effects*
  • Helicobacter pylori / enzymology
  • Humans
  • Japan
  • Levofloxacin*
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Mutation*
  • Ofloxacin / pharmacology*
  • Sequence Analysis, DNA

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • DNA, Bacterial
  • Levofloxacin
  • Ofloxacin
  • DNA Gyrase