title: 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.
authors.affiliation: Mitsushige Sugimoto, First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Mitsushige Sugimoto, First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furuta
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017291:Clarithromycin / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori; D006801:Humans; D008826:Microbial Sensitivity Tests; D011110:Polymorphism, Genetic; D015995:Prevalence; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D054328:Proton Pump Inhibitors; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D017291:Clarithromycin
keywords: Clarithromycin; Cytochrome P450 2C19; Helicobacter pylori; Proton pomp inhibitor; Tailored eradication therapy