Recent advances in Helicobacter pylori eradication

Th e 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 infl uence the success or failure of H. pylori eradication: duration of therapy and dosage, PPI eff ect on gastric acid secretion, other drugs’ resistance, and patients’ compliance. Regardless of the antibiotic used, prolonging treatment duration from 7 to 14 days signifi cantly 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 eff ective 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 aff ect 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, Bifi dobacterium and Saccharomyces boulardii-containing probiotic compounds given together with antibiotics, increased the eradication rate and reduced treatment-associated side eff ects, particularly diarrhea [8,9]. To overcome the limitations of triple therapy, several fi rstline 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 fl uoroquinolones are usually reserved for salvage therapy, they are also eff ective as fi rst-line therapy. In 9 randomized controlled trials levofl oxacin-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 fi rst regimens used for H. pylori eradication [12]. Th e success rate was very poor, thus neglected till today, when high-dose dual therapy (HDDT) was described with a signifi cant 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 eff ective. 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 diff er 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]. Th ey concluded that the 10-day high-dose dual therapy with esomeprazole plus AMOX might be an eff ective and safe fi rst-line regimen. However, as the authors themselves point out, adequate randomized controlled trials evaluating this regimen are warranted.