An update on current and advancing pharmacotherapy options for the treatment of H. pylori infection

ABSTRACT

Introduction: Eradication of Helicobacter pylori (H. pylori) becomes more challenging due to increasing antimicrobial resistance. Consequently, the performance of clarithromycin-containing triple therapies is now declining to unacceptable levels and should be abandoned unless a prior susceptibility test precludes clarithromycin resistance.

Areas covered: This review summarizes updated evidence concerning new and advancing pharmacotherapy options for H. pylori eradication.

Expert opinion: Due to the declining efficacy of legacy triple therapies, most guidelines recommend bismuth quadruple therapy as the best initial empiric treatment. Concomitant, sequential and hybrid therapies are remarkable bismuth-free quadruple options, provided that dual clarithromycin-metronidazole resistance is low. Levofloxacin-, rifabutin-, furazolidone- and sitafloxacin-containing regimens remain useful, particularly as salvage options. To eradicate H. pylori in line with the rules of antibiotic stewardship, susceptibility-guided treatment appears as the ideal approach. However, the feasibility and cost-effectiveness of universal pre-treatment susceptibility testing warrants further evaluation. Molecular testing methods promise convenient characterization of H. pylori antibiotic susceptibility. High-dose dual therapy (proton-pump-inhibitor plus amoxicillin) and vonoprazan, a more potent acid inhibitor that likely enhances the activity of amoxicillin, are promising alternatives that could decrease misuse of antibiotics. Addition of certain probiotics could somewhat increase the performance of H. pylori eradication regimens, while improving tolerability.

KEYWORDS:

• Helicobacter pylori
• concomitant
• hybrid
• probiotics
• vonoprazan

Article highlights

• In most parts of the world, increasing resistance to key antibiotics is currently the main concern in the field of H. pylori infection, leading to therapeutic regimens failure.

• Bismuth-containing therapies offer the best possibility for first-line eradication, showing high efficiency and a clear superiority over non-bismuth-containing regimens at least in extremely high antimicrobial resistance areas (>15% dual resistance).

• Among bismuth-free quadruple therapies, concomitant therapy is currently designated as the preferred option, mainly due to its better efficacy against strains of H. pylori with dual resistance.

• High-dose dual therapy with high doses of PPIs and frequent and high amoxicillin dosing gains renewed interest as an effective therapy, mostly used as a salvage option.

• To eradicate H. pylori in line with the rules of antibiotic stewardship, susceptibility-guided treatment appears as the ideal approach. However, the feasibility and cost-effectiveness of universal pre-treatment susceptibility testing warrants further evaluation.

• Vonoprazan, a more potent acid inhibitor compared to PPIs, offers a brand new perspective in the field of H. pylori, likely by enhancing the activity of amoxicillin.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

One reviewer is a consultant for RedHill Biopharma and Phathom Pharmaceuticals regarding novel H. pylori therapies and has received research support for culture of Helicobacter pylori. They are also an investigator of an international study of the use of antimycobacterial therapy for Crohn’s disease. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.