Treatment of Helicobacter pylori

Abstract

Recognition in the last 12 years that H. pylori is a common infection which causes the majority of peptic ulcers and many gastric cancers has revolutionised understanding of these diseases. However, genuinely novel treatments have in the main not yet emerged. Eradication of H. pylori is difficult because of the problems of delivering bactericidal levels of antibiotics to the gastric mucus where the organism resides, because of the emergence of resistance to nitroimidazoles and clarithromycin, and possibly because H. pylori can assume a resting coccoid form which is not susceptible to antibiotic treatment. To date, eradication treatment has been based upon the use of existing antibiotics employed in intensive multi-drug regimes of three basic types. Bismuth-based triple therapy employed ampicillin or a nitroimidazole, tetracycline and bismuth and achieved eradication rates of approximately 80%. Dual therapy in which amoxycillin was added to omeprazole was briefly popular because of its greater simplicity but fell from favour when it was realised that eradication rates were considerably lower. However, the recognition that proton pump inhibitors enhance eradication by either direct or indirect mechanisms led to the development of what is currently the most effective treatment - proton pump-based triple therapy in which a nitroimidazole or amoxycillin is combined with a proton pump inhibitor and clarithromycin. Such regimes achieve approximately 90% eradication. So far, the only therapy specifically developed for the treatment of H. pylori is ranitidine bismuth citrate (Pylorid). This new chemical entity based on ranitidine and bismuth citrate uses the antibacterial effects of bismuth to kill H. pylori but requires co-administration of another antibiotic to achieve reasonable eradication rates. In the future, further novel, specific anti-Helicobacter treatment can be expected, as a result of strategies targeted at key virulence factors or metabolic pathways such as the organism's urease, adhesin, cytotoxin, oxidase or nitro reductase activities. Some of these strategies will involve vaccination. Other possible approaches include targeting the coccoid form, achieving single treatment eradication and more effective gastric mucus delivery systems.