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[幽门螺杆菌与阿奇霉素]

[Helicobacter pylori and azithromycin].

作者信息

Mégraud F, Darmaillac V, Brügmann D

机构信息

Laboratoire de Bactériologie, Hôpital Pellegrin, Bordeaux, France.

出版信息

Pathol Biol (Paris). 1995 Jun;43(6):555-60.

PMID:8539082
Abstract

Helicobacter pylori is a Gram-negative bacterium with man as the unique reservoir and where the niche is the stomach. Transmission between individuals could be by fecal and oral route. In the stomach, the bacterium is mainly located at the mucus level and adhere to antral cells which are the privileged target. Within the colonized mucosa, H. pylori generates or secretes different deleterious compounds against the epithelial cells: urease, hydrolyzing urea into ammonia, a cytotoxic agent: monochloramine also cytotoxic, various enzymes and a vacuolyzing cytotoxin; all of these also contribute to the pathogenic potential. In addition the associated inflammatory reaction probably plays a part in the lesion process. One important consequence is peptic ulcer disease and particularly duodenal ulcer which can further degenerate into a precancer lesion and to a lesser extent some dyspeptic syndromes. Bacterial eradication can be obtained by the combination of an antisecretory drug with an antibiotic. Macrolides have a good activity against this bacterium. The azithromycin MIC50 is 0.12 mg/l. A bactericidal activity is observed at concentrations equal or higher than 0.10 mg/l. After a single dose of 500 mg, azithromycin concentrations are 0.48 micrograms/g in the mucus and 4 micrograms/g in the gastric tissue. Concentrations persist for a long time, due to long half life (3 days). In pilot clinical trials, with a tritherapy combining azithromycin with metronidazole and omeprazole, 80% of bacterial eradication was obtained. These promising need to be validated by larger clinical trials.

摘要

幽门螺杆菌是一种革兰氏阴性菌,唯一宿主为人,其生存环境是胃部。人与人之间的传播途径可能是粪口途径。在胃内,该细菌主要位于黏液层,并黏附于作为优先靶点的胃窦细胞。在被定植的黏膜内,幽门螺杆菌产生或分泌针对上皮细胞的不同有害化合物:尿素酶,将尿素水解为氨,一种细胞毒性剂;一氯胺也具有细胞毒性;还有各种酶和一种空泡化细胞毒素;所有这些也都促成了致病潜力。此外,相关的炎症反应可能在病变过程中起作用。一个重要后果是消化性溃疡疾病,尤其是十二指肠溃疡,其可进一步恶化为癌前病变,在较小程度上还可导致一些消化不良综合征。通过将抗分泌药物与抗生素联合使用可实现细菌根除。大环内酯类药物对这种细菌具有良好活性。阿奇霉素的MIC50为0.12mg/l。在浓度等于或高于0.10mg/l时可观察到杀菌活性。单次服用500mg后,阿奇霉素在黏液中的浓度为0.48微克/克,在胃组织中的浓度为4微克/克。由于半衰期长(3天),浓度可长时间持续。在试点临床试验中,采用阿奇霉素与甲硝唑和奥美拉唑联合的三联疗法,细菌根除率达到了80%。这些有前景的结果需要通过更大规模的临床试验来验证。

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