title: Helicobacter pylori infection: a randomized, controlled study comparing 2 rescue therapies after failure of standard triple therapies.
abstract: Antibiotic resistance to amoxicillin in second-line eradication therapy for Helicobacter pylori infection is much less frequent than resistance to metronidazole. We conducted a randomized, controlled study to compare the efficacies of standard quadruple rescue therapy and a new therapy with amoxicillin replacing metronidazole for patients failing first-line eradication treatment. We randomly assigned 120 patients who failed H. pylori eradication using a proton pump inhibitor plus clarithromycin and amoxicillin to undergo a 1-week rescue therapy with esomeprazole, bismuth subcitrate, and tetracycline plus either metronidazole (EBTM group, n = 62) or amoxicillin (EBTA group, n = 58). We used follow-up endoscopy 8 weeks after the end of treatment to assess the treatment response. We also examined and analyzed antibiotic resistances and CYP2C19 genotypes. Intention-to-treat analysis demonstrated that the EBTA group had a significantly lower eradication rate than the EBTM group (62% vs. 81%, respectively, p = 0.02). Per-protocol analysis showed similar results (64% vs. 83%, p = 0.01). However, the EBTA group had less frequency of adverse events than the EBTM group (19% vs. 44%, p < 0.01). Both groups had good drug compliance (both 97%). Antibiotic susceptibility tests showed that the frequency of amoxicillin-resistant strains was much less than that of metronidazole-resistant strains (0% vs. 54%, respectively), and there were no significant differences between H. pylori eradication rates and antibiotic resistances. In conclusion, EBTA quadruple therapy demonstrated a lower eradication rate than standard EBTM therapy in second-line rescue treatment. The discrepancy between in vitro antibiotic susceptibility and in vivo eradication response is probably due to drug interactions between combined antibiotics or some unknown causes, and should not be neglected in H. pylori therapy.
authors.affiliation: From Division of Gastroenterology (D-CW, C-HK, S-WW), Department of Internal Medicine; and Cancer Center (D-CW), Kaohsiung Medical University Hospital, Kaohsiung; Department of Medicine (D-CW), Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung; Division of Gastroenterology (P-IH, F-WT, K-HL), Department of Internal Medicine; and Department of Pathology (H-HT), Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung; Institute of Biomedical Sciences (AC), National Sun Yat-Sen University, Kaohsiung; and Department of General Medicine (P-IH), College of Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Deng-Chyang
authors.initials: DC
authors.lastname: Wu
authors.forename: Ping-I
authors.initials: PI
authors.lastname: Hsu
authors.forename: Hui-Hwa
authors.initials: HH
authors.lastname: Tseng
authors.forename: Feng-Woei
authors.initials: FW
authors.lastname: Tsay
authors.forename: Kwok-Hung
authors.initials: KH
authors.lastname: Lai
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Kuo
authors.forename: Sheng-Wen
authors.initials: SW
authors.lastname: Wang
authors.forename: Angela
authors.initials: A
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000009:adverse effects / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D064098:Esomeprazole / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000235:genetics; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009942:Organometallic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D011110:Polymorphism, Genetic / Q000235:genetics; D013752:Tetracycline / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D009942:Organometallic Compounds; D008795:Metronidazole; D000658:Amoxicillin; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013752:Tetracycline; C002791:bismuth tripotassium dicitrate; D064098:Esomeprazole