Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea.
Helicobacter. 2011 Aug;16(4):301-10. doi: 10.1111/j.1523-5378.2011.00840.x.
Fluoroquinolone resistance of Helicobacter pylori is known to be dependent on mutations in the QRDR of gyrA. This study was performed to investigate the distribution of gyrA point mutations and to evaluate the impact of the mutations on second-line H. pylori eradication therapy.
After H. pylori isolation from gastric mucosal specimens, fluoroquinolone resistance was examined using the agar dilution method. DNA sequencing of the QRDR of gyrA was performed in 89 fluoroquinolone-resistant and 27 fluoroquinolone-susceptible isolates. Transformation experiments were performed to confirm mutations in the resistant strains. The eradication rates of moxifloxacin-containing triple therapy were evaluated depending on the resistance of fluoroquinolone.
The gyrA mutations were detected in 75.3% (55 of 73 strains) of the primary resistant strains and 100% (16 strains) of the secondary resistant strains. The most common mutations were Asp-91 (36.0%) and Asn-87 (33.7%). The MIC values in the transformed strains differed depending on the gyrA mutations, N87, and D91. Six patients with fluoroquinolone-resistant strains received moxifloxacin-containing triple therapy as the second-line therapy, and two of three patients with Asn-87 mutations (66.7%) failed in the eradication. By contrast, three patients with Asp-91 mutations had successful eradication treatment.
Fluoroquinolone resistance of H. pylori was caused by gyrA Asn-87 and Asp-91 point mutations. The Asn-87 mutation seems to be an important determinant of failure of fluoroquinolone-containing triple eradication therapy based on eradication results.
已知幽门螺杆菌（Helicobacter pylori）的氟喹诺酮耐药性取决于 gyrA 的 QRDR 中的突变。本研究旨在调查 gyrA 点突变的分布，并评估突变对二线 H. pylori 根除治疗的影响。
从胃黏膜标本中分离出 H. pylori 后，采用琼脂稀释法检测氟喹诺酮耐药性。对 89 株氟喹诺酮耐药株和 27 株氟喹诺酮敏感株的 gyrA QRDR 进行 DNA 测序。在耐药株中进行转化实验以确认突变。根据氟喹诺酮的耐药性评估包含莫西沙星的三联疗法的根除率。
在 75.3%（73 株中的 55 株）的原发性耐药株和 100%（16 株）的继发性耐药株中检测到 gyrA 突变。最常见的突变是 Asp-91（36.0%）和 Asn-87（33.7%）。转化株的 MIC 值因 gyrA 突变、N87 和 D91 而异。6 名氟喹诺酮耐药株患者接受包含莫西沙星的三联疗法作为二线治疗，3 名 Asn-87 突变患者中有 2 名（66.7%）根除失败。相比之下，3 名 Asp-91 突变患者的根除治疗取得成功。
H. pylori 的氟喹诺酮耐药性是由 gyrA Asn-87 和 Asp-91 点突变引起的。基于根除结果，Asn-87 突变似乎是氟喹诺酮包含三联根除疗法失败的重要决定因素。
