title: High rate of post-therapeutic resistance after failure of macrolide-nitroimidazole triple therapy to cure Helicobacter pylori infection: impact of two second-line therapies in a randomized study.
abstract: BACKGROUND
  The optimal second-line treatment after failed Helicobacter pylori therapy has not been established.
  
  
  OBJECTIVE
  To ascertain whether quadruple therapy or triple therapy with omeprazole, clarithromycin and amoxicillin is the superior re-treatment after triple therapy containing a macrolide and a nitroimidazole, and to determine the impact of microbial in vitro resistance.
  
  
  METHODS
  Patients after failed triple therapy were randomly allocated to one of two 1-week second-line treatments: omeprazole, 40 mg, clarithromycin, 500 mg, and amoxicillin, 1 g, all b.d.; or omeprazole, 20 mg b.d., bismuth subsalicylate, 600 mg q.d.s., metronidazole, 400 mg t.d.s., and tetracycline, 500 mg q.d.s. Post-therapeutic Helicobacter pylori status was assessed by 13C-urea breath test at least 4 weeks after treatment.
  
  
  RESULTS
  The study was terminated after including 84 patients. H. pylori cure rates differed significantly: omeprazole-clarithromycin-amoxicillin: intention-to-treat, 43%; per protocol, 50%; omeprazole-bismuth subsalicylate-metronidazole-tetracycline: intention-to-treat, 68%; per protocol, 69%. The frequencies of resistance after first-line therapy were: metronidazole, 90%; clarithromycin, 71%; both combined, 68%. For clarithromycin resistance, H. pylori cure with omeprazole-clarithromycin-amoxicillin was 30% vs. 83% for clarithromycin susceptibility.
  
  
  CONCLUSIONS
  Omeprazole-bismuth subsalicylate-metron- idazole-tetracycline was superior to omeprazole-clarithromycin-amoxicillin, but both therapies yielded unsatisfactory results. The high rate of post-therapeutic dual resistance has a negative impact on omepraz- ole-clarithromycin-amoxicillin, and probably also on omeprazole-bismuth subsalicylate-metronidazole-tetracycline, and limits the choice for second-line treatment.
authors.affiliation: Department of Gastroenterology, Hepatology and Infectiology, Otto-von-Guericke University of Magdeburg, Leipziger Strasse 44, D39120 Magdeburg, Germany. ulrich.peitz@medizin.uni-magdeburg.de
authors.forename: Ulrich
authors.initials: U
authors.lastname: Peitz
authors.forename: M
authors.initials: M
authors.lastname: Sulliga
authors.forename: K
authors.initials: K
authors.lastname: Wolle
authors.forename: A
authors.initials: A
authors.lastname: Leodolter
authors.forename: U
authors.initials: U
authors.lastname: Von Arnim
authors.forename: S
authors.initials: S
authors.lastname: Kahl
authors.forename: M
authors.initials: M
authors.lastname: Stolte
authors.forename: G
authors.initials: G
authors.lastname: Börsch
authors.forename: J
authors.initials: J
authors.lastname: Labenz
authors.forename: P
authors.initials: P
authors.lastname: Malfertheiner
mesh_terms: D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000008:administration & dosage / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001944:Breath Tests; D017291:Clarithromycin / Q000008:administration & dosage / Q000627:therapeutic use; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000473:pathology; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009593:Nitroimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D009853:Omeprazole / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D009593:Nitroimidazoles; D000658:Amoxicillin; D017291:Clarithromycin; D009853:Omeprazole