Recent advances in Helicobacter pylori eradication

The most popular regimen for eradication of Helicobacter pylori (H. pylori) infection is triple therapy, composed of a potent proton pump inhibitor (PPI), amoxicillin (AMOX), and clarithromycin (CLA). Emerging resistance to CLA changed this strategy, and according to Maastricht IV recommendation, this regimen can be used only in countries with low (<20%) CLA resistance [1]. A regimen for the treatment of H. pylori is now acceptable if it is associated with at least 90% success [2].

In addition to CLA resistance several other factors may influence the success or failure of H. pylori eradication: duration of therapy and dosage, PPI effect on gastric acid secretion, other drugs’ resistance, and patients’ compliance. Regardless of the antibiotic used, prolonging treatment duration from 7 to 14 days significantly improved eradication rates [3]. PPI is an important part of the treatment protocol, since a gastric higher pH is essential for antibiotics function. Esomeprazole is more effective in acid inhibition and H. pylori eradication than other PPIs such as omeprazole, lansoprazole and pantoprazole, especially in patients with polymorphisms in S-mephenytoin 4’-hydroxylase (CYP2C19) associated with extensive PPI metabolism [4]. Several single nucleotide polymorphisms in the CYP2C19 gene, which affect gene function, lead to rapid or slow PPI metabolism. In extensive metabolizers H. pylori eradication rate may be improved by increasing PPI dosage or by reducing the intervals between the doses [5]. Treatment may be individualized by testing susceptibility to antibiotics. Four single nucleotide polymorphisms are responsible for most resistance to CLA and may be tested in gastric or stool samples [6]. Culture-guided therapy yields superior eradication rates [7].

Lactobacillus, Bifidobacterium and Saccharomyces boulardii-containing probiotic compounds given together with antibiotics, increased the eradication rate and reduced treatment-associated side effects, particularly diarrhea [8,9].

To overcome the limitations of triple therapy, several first-line regimens are available such as quadruple therapy with nitroimidazole or bismuth, sequential therapy [AMOX-PPI for 5-7 days, followed by CLA-metronidazole (MET)-PPI for 5-7 days], concomitant therapy (AMOX-CLA-MET-PPI taken together for 10-14 days), hybrid therapy (AMOX-PPI for the entire duration of treatment, while adding CLA-MET for the second half alone) [10]. Although fluoroquinolones are usually reserved for salvage therapy, they are also effective as first-line therapy. In 9 randomized controlled trials levofloxacin-based therapy was superior to regular triple therapy, regardless of treatment duration [11]. Clinicians must consider antibiotic resistance patterns in their population before choosing a particular regimen.

Dual therapy with a PPI and AMOX was one of the first regimens used for H. pylori eradication [12]. The success rate was very poor, thus neglected till today, when high-dose dual therapy (HDDT) was described with a significant success. Since H. pylori resistance to AMOX in both treatment-naïve and experienced patients is very rare, the only obstacle for the antibiotics is the gastric pH. Higher dose and longer duration, at least theoretically, make HDDT very effective. In Asia HDDT achieved 95.3% eradication compared to 85.3% with sequential therapy [12,13]. Since many factors are responsible for the success of H. pylori eradication, the results of HDDT may differ between populations. Trials that examine this issue are therefore required. Towards this end, in this issue of Annals of Gastroenterology, an Italian group performed a prospective, multicenter trial, studying the concept of HDDT in Europe [14]. They concluded that the 10-day high-dose dual therapy with esomeprazole plus AMOX might be an effective and safe first-line regimen. However, as the authors themselves point out, adequate randomized controlled trials evaluating this regimen are warranted.