Ohara T, Goshi S, Taneike I, Tamura Y, Zhang H M, Yamamoto T
Department of Bacteriology, School of Medicine, Niigata University, Niigata, Japan.
Helicobacter. 2001 Jun;6(2):125-9. doi: 10.1046/j.1523-5378.2001.00018.x.
Clarithromycin-resistant Helicobacter pylori (CRHP) has increasingly been isolated from patients in Japan. The aim of our study was to test whether proton pump inhibitors (PPIs) and their thioether derivatives, which are secreted into the gastric mucosa, could inhibit the growth and motility (a factor in colonization) of CRHP.
CRHP was isolated from patients who had experienced gastritis or peptic ulcers in Tokyo and Niigata. Drugs and related agents tested were omeprazole, lansoprazole, rabeprazole, the thioether derivative of rabeprazole (rabeprazole-TH), clarithromycin, amoxicillin and metronidazole. The MICs of the drugs and agents for H. pylori strains were determined by the agar dilution
Bacterial swimming in a liquid layer was examined under an inverted, phase-contrast microscope.
The PPIs and rabeprazole-TH, but not the anti-H. pylori agents, inhibited the motility of CRHP at both pH 7.4 and 6.0. The concentrations (microg/ml) necessary to inhibit 50% of the motility at pH 7.4 were 0.25-0.5, 8-32, 8-16 and 128-256 for rabeprazole-TH, rabeprazole, lansoprazole and omeprazole, respectively. Rabeprazole-TH exhibited the strongest inhibitory effect against the growth of CRPH (MIC, 0.5 microg/ml).
Rabeprazole-TH, which is secreted into the gastric mucosa, had the strongest inhibitory action against both the growth and motility of CRHP, suggesting that it is a potential novel agent for CRHP eradication.
在日本,已越来越多地从患者中分离出对克拉霉素耐药的幽门螺杆菌(CRHP)。我们研究的目的是测试分泌到胃黏膜中的质子泵抑制剂(PPI)及其硫醚衍生物是否能抑制CRHP的生长和运动性(定植的一个因素)。
从东京和新泻患有胃炎或消化性溃疡的患者中分离出CRHP。所测试的药物及相关制剂有奥美拉唑、兰索拉唑、雷贝拉唑、雷贝拉唑的硫醚衍生物(雷贝拉唑-TH)、克拉霉素、阿莫西林和甲硝唑。通过琼脂稀释法测定这些药物及制剂对幽门螺杆菌菌株的最低抑菌浓度(MIC)。通过倒置相差显微镜观察细菌在液体层中的游动情况。
PPI和雷贝拉唑-TH,而非抗幽门螺杆菌药物,在pH 7.4和6.0时均能抑制CRHP的运动性。在pH 7.4时抑制50%运动性所需的浓度(μg/ml),雷贝拉唑-TH为0.25 - 0.5,雷贝拉唑为8 - 32,兰索拉唑为8 - 16,奥美拉唑为128 - 256。雷贝拉唑-TH对CRPH的生长表现出最强的抑制作用(MIC,0.5μg/ml)。
分泌到胃黏膜中的雷贝拉唑-TH对CRHP的生长和运动性均具有最强的抑制作用,表明它是一种潜在的根除CRHP的新型药物。