Treatment of Helicobacter pylori infection - A review

Abstract

The realization that Helicobacter pylori infection is one of the most important etiological factors for peptic ulcer has had an enormous impact on approach to the management of ulcer disease. Today, there is no longer any serious debate about the value or appropriateness of treatment of H. pylori in patients with peptic ulcer or low-grade mucosa associated lymphoid tissue (MALT) lymphoma. Many antimicrobial agents have been studied for their efficacy in eradicating H. pylori infection either as a single agent or as a combination therapy. Single drug regimens are not advocated due to the potential for the development of antibiotic resistance especially to macrolides and nitroimidazoles, which are the key antimicrobial agents in the multi-drug regimens for H. pylori. Dual treatments combining a proton pump inhibitor (PPI) with either clarithromycin or amoxicillin were popular a few years ago as they were easy to explain and well tolerated. They have now been abandoned because of unacceptly low eradication rates. Bismuth based triple therapy consisting of colloidal bismuth subcitrate, tetracycline and metronidazole for two weeks is cheap, well investigated and reaches high cure rates in metronidazole sensitive strains. Even though bismuth based triple therapies have high and acceptable eradication rates in areas with low nitromidazole resistance, in developing countries the response to this therapy is low as 80-90% of H. pylori strains are resistant to metronidazole. Triple therapies with a combination of a PPI and two antibiotics have largely replaced the use of the classical bismuth based triple therapy in almost all countries due to better tolerability and higher efficacy. Proton pump inhibitors have a synergistic effect with several antibiotics by raising the pH and making it optimal for the activity of the other antibiotics. These therapies of PPI in combination with two antibiotics are advocated as a 7-14 day regimens with omeprazole, lansoprazole or pantoprazole in combination with two of the following agents viz. clarithromycin, amoxicillin and metronidazole (or tinidazole). PPI based triple therapies are usually considered the first line of treatment. When resistance to nitroimidazoles is high, then a combination of PPI with amoxicillin and clarithromycin is preferred. A new group of triple regimens has been developed that replaces PPI with ranitidine bismuth citrate (RBC). These produce less acid suppression but provide the additional antimicrobial action of bismuth. RBC has been shown in vitro to have both inhibitory and bactericidal activity against H. pylori. In an attempt to achieve 100% eradication of H. pylori, a quadruple therapy combination by addition of anti-secretory agents like PPI to the classic triple therapy has been done. The major advantages of this regimen over the classical triple therapy are high and consistent eradication rates, a one week treatment offering a cure rate similar to a two week therapy and a significant reduction in complications seen with the two week bismuth based triple therapy as the total duration of therapy is reduced. This regimen is also recommended as the rescue line therapy when the first line therapy fails. Increasing our understanding of the mechanisms by which bacterial eradication is achieved is the key to optimizing treatment of H. pylori infection.