Efficacy of tailored Helicobacter pylori eradication therapy based on antibiotic susceptibility and CYP2C19 genotype

Abstract

The cure rates of Helicobacter pylori (H. pylori) eradication therapy using a proton pump inhibitor (PPI) and antimicrobial agents such as amoxicillin, clarithromycin, and metronidazole are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of the inhibition of acid secretion. Annual cure rates have gradually decreased because of the increased prevalence of H. pylori strains resistant to antimicrobial agents, especially to clarithromycin. Alternative regimens have therefore been developed incorporating different antimicrobial agents. Further, standard PPI therapy (twice-daily dosing) often fails to induce a long-term increase in intragastric pH > 4.0. Increasing the eradication rate requires more frequent and higher doses of PPIs. Therapeutic efficacy related to acid secretion is influenced by genetic factors such as variants of the genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19, CYP2C19), drug transporters (e.g., multidrug resistance protein-1; ABCB1), and inflammatory cytokines (e.g., interleukin-1β). For example, quadruple daily administration of PPI therapy potently inhibits acid secretion within 24 h, irrespective of CYP2C19 genotype. Therefore, tailored H. pylori eradication regimens that address acid secretion and employ optimal antimicrobial agents based on results of antimicrobial agent-susceptibility testing may prove effective in attaining higher eradication rates.

Keywords: Helicobacter pylori, Tailored eradication therapy, Proton pomp inhibitor, Cytochrome P450 2C19, Clarithromycin

Core tip: The eradication for Helicobacter pylori infection is mainly influenced by antibiotic susceptibility and insufficient acid inhibition [e.g., cytochrome P450 2C19 (CYP2C19) genotype, proton pump inhibitor (PPI) dose, and PPI treatment schedule]. When a PPI is administered to CYP2C19 rapid metabolizers and intermediate metabolizers, plasma levels of PPIs cannot be maintained between once-daily doses. The intragastric pH attained with four-times-daily-dosing of PPI is significantly higher than those observed when PPI is administered as once-daily-dosing of four-fold doses or twice-daily-dosing of two-fold doses. We describe a tailored treatment that was designed according to pharmacogenomics and antimicrobial susceptibility to achieve an eradication rate exceeding 95%, irrespective of different CYP2C19 genotypes.