Primary Levofloxacin Resistance and gyrA/B Mutations Among Helicobacter pylori in Japan

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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.

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