Personalized treatment in the eradication therapy for Helicobacter pylori.
Helicobacter pylori (HP) is known to be a causative bacterium of gastritis and peptic ulcers. The combination treatment consisting of a proton pump inhibitor (PPI), amoxicillin and clarithromycin (CAM) is widely used in eradication therapy, but the eradication fails in some patients. The main causes are CAM resistance of HP and individual variability in PPI metabolism related to the activity of the cytochrome P450 2C19 (CYP2C19) enzyme. In this study, we examined the usefulness of the prediction of the pharmacotherapeutic efficacy using a newly developed analysis system for HP CAM resistance and CYP2C19 genotypes. After obtaining the informed consent from 45 subjects with HP-positive peptic ulcers, biopsy specimens of the gastric mucosa were obtained by endoscopy. HP DNA extracted from the gastric mucosa was examined by the SELMAP-PCR method, the direct sequencing method or the single-nucleotide primer extension (SNuPE) method. HP detection rates by culture and the SELMAP-PCR method were 71% and 100%, respectively. Among 32 cultured HP, CAM resistance was confirmed in 6 samples by the in vitro drug susceptibility test. CAM-resistant gene mutations were also examined by the SELMAP-PCR method using 32 DNAs from cultured HP and the results were consistent with the drug susceptibility test. Among 22 patients, the eradication rate was 77%. Among 4 patients with CAM resistance determined by both the in vitro drug susceptibility test and the SNuPE method, eradication was successful in one intermediate metabolizer (IM), but not in three extensive metabolizers (EMs). Patients were divided into three groups according to their CYP2C19 phenotype: EMs, IMs and poor metabolizers (PMs). The eradication rates for 6 EMs, 12 IMs and 4 PMs were 33.3%, 91.7% and 100%, respectively. Based on these results, the information on CAM resistance in HP and CYP2C19 phenotypes in carriers could predict the pharmacotherapeutic efficacy and probability of eradication. It can then be possible to vary the dosing or to select another drug by the prediction of the pharmacotherapeutic efficacy.
Department of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Sayaka
S
Jinda
Kaname
K
Nakatani
Junji
J
Nishioka
Kazunari
K
Yasuda
Yoshihiro
Y
Soya
Amiko
A
Hayashi
Hideo
H
Wada
Tsutomu
T
Nobori
D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D017291:Clarithromycin / Q000494:pharmacology* / Q000627:therapeutic use; D065731:Cytochrome P-450 CYP2C19; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005753:Gastric Mucosa / Q000382:microbiology; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy / Q000235:genetics; D016480:Helicobacter pylori / Q000187:drug effects / Q000235:genetics; D006801:Humans; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine / Q000379:methods*; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D017291:Clarithromycin