DNA sequence analysis of mutations associated with resistance to clarithromycin and quinolone in Helicobacter pylori

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概要

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• Background : Currently, the mainstay of Helicobacter pylori (H. pylori) eradication therapy is a combination of amoxicillin (AMPC), clarithromycin (CAM), and lansoprazole, which achieves an eradication rate as high as 80%-90%. However, this means that the combination fails in some patients. Materials and Methods : Changes of the sensitivity to 12 drugs among 122 clinical isolates obtained from 2000 through 2001 were assessed, mutations of DNA gyrase/gyrA, 23S rRNA, 16S rRNA, and cagPAI associated with antimicrobial resistance (MIC >__- 2-4μg/mL) were identified, and pulsed-field gel electrophoresis (PFGE) was performed. Results : Some of the isolates from 2000 through 2001 showed an increased MIC_<90> for AMPC (0.5μg/mL), a component of the triple therapy currently used for H. pylori eradication. CAM showed a decrease of antimicrobial activity, with an MIC_<90> of <__- 0.063μg/mL for the 1996 isolates versus 2μg/mL for those from 2000 through 2001. Similarly, the MIC_<90> of levofloxacin (LVFX) for the isolates from the same period was increased to 4μg/mL. The mechanism of resistance in these strains was investigated by PCR analysis of the relevant genes. Among the cagPAI, DNA gyrase/gyrA, 23S rRNA, and 16S rRNA regions, Asp91Tyr or Asp91Gly mutations were found in DNA gyrase/gyrA of LVFX-resistant clinical isolates (by comparison with BLAST 22105162A), while the 23S rRNA of CAM-resistant strains showed an Ala2515Gly mutation (by comparison with GenBank U27270). On the other hand, no mutations of 16S rRNA and 23S rRNA were observed. Conclusion : H. pylori eradication therapy is still beneficial, but resistance to CAM and AMPC is gradually increasing. The increase of CAM-resistant strains may be attributed to widespread use of macrolides for non-H. pylori infections in the fields of otolaryngology and respiratory disease (e.g., recurrent diffuse bronchitis). A further increase of CAM-resistant H. pylori would be problematic, therefore, measures should be taken to prevent it.

• 北里大学の論文
• 2005-09-30

著者

• INOUE Matsuhisa

  Department of Microbiology, Kitasato University

• Inoue Matsuhisa

  帝京大学 医学部

• Inoue Matsuhisa

  北里大学 医療系研究科環境感染学

• Inoue Matsuhisa

  北里大学 医学部生化学

• Inoue Matsuhisa

  長崎大学 医歯薬総研究耳鼻咽喉病態制御学

• IRINODA Kazuhiko

  Department of Microbiology, Kitasato University School of Medicine

• Inoue Matsuhisa

  Department Of Microbiology And Parasitology Kitasato University School Of Medicine

• Hosaka Yoshio

  Department of Microbiology and Parasitology, Kitasato University School of Medicine

• Yano Hisakazu

  Department Of Microbiology Kitasato University School Of Medicine

• Inoue M

  Kitasato Univ. School Of Medicine Kanagawa Jpn

• Hosaka Yoshio

  Department Of Microbiology And Parasitology Kitasato University School Of Medicine

• Inoue Matsuhisa

  Department Of Microbiology Kitasato University School Of Medicine

• Irinoda Kazuhiko

  Department Of Microbiology And Parasitology Kitasato University School Of Medicine

• Irinoda Kazuhiko

  Department Of Microbiology Kitasato University School Of Medicine

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