Therapy and drug resistance in Helicobacter pylori infection (original) (raw)

Eradication of Helicobacter pylori (H. pylori) is attempted in many disease conditions and could be the means of preventing gastric cancer, but it is difficult to achieve. At present, there are no single agents capable of curing the infection, and combination regimens are needed to eradicate H. pylori. Many agents, including antibiotics and antisecretory agents, have been used and those that have resulted from different combinations of agents are numberless. However, they can be grouped into a few major categories. The so-called standard, or bismuth based, triple therapy comprises bismuth, metronidazole and tetracycline. This regimen can achieve high eradication rates and because of its low cost, has also been considered, for years, as the gold standard; however, because of its complexity and sometimes severe side-effects, its effectiveness is limited and significantly lower eradication rates appear when properly calculated by the intention-to-treat analysis. Dual therapy is another landmark in H. pylori eradication. Dual therapies comprise a proton pump inhibitor (PPI) plus one antibiotic; initially, it was amoxycillin, later clarithromycin was used. Preliminary studies claimed that omeprazole plus amoxycillin, administered for two weeks, could eradicate H. pylori in more than 90% of the cases. However, subsequent studies produced inconsistent results and accepted eradication rates by dual therapies are less than 60%. Both standard triple and dual therapies, however, in spite of their low applicability, should be considered as milestones because they have provided the background rationale for the development of short-term low-dose PPI triple therapies. A simple, safe, short-term low-dose triple therapy including a PPI and two antibiotics, has been developed in response to the problems encountered with standard triple and dual therapies. In fact, an analysis of the many studies in the literature has shown that, in addition to the hostile gastric environment that reduces bioavailability of antibiotics in the stomach, two other factors, namely side effects and patient non-compliance were significantly associated with treatment failure. These observations led to the hypothesis that by increasing the intragastric pH with a PPI and by using two antibiotics of high efficacy and low MIC, at low dosages and with a small number of tablets, drug availability would be increased, side-effects reduced and compliance improved. Initial eradication rates reported by this regimen and approaching 100% were regarded with skepticism; however, soon afterwards, many other authors from different countries were able to confirm the excellent performance of regimens based on the principle of administering a PPI plus two antibiotics, clarithromycin, metronidazole or amoxycillin, for one week. Furthermore, some time later, the rationale of adding a PPI and reducing the administration period to one week was also applied to the standard bismuth triple therapy resulting in the so-called quadruple therapy, nowadays the other well-established regimen for H. pylori eradication. The continuous flow of data in the literature confirms that the above-mentioned regimens should still be considered for the treatment of H. pylori. Nevertheless, there are many factors affecting H. pylori eradication, including not only side-effects and patient compliance, but also disease condition [peptic ulcer disease (PUD), non ulcer dyspepsia (NUD), etc.], different ge-5207