title: The importance of the level of metronidazole resistance for the success of Helicobacter pylori eradication.
abstract: OBJECTIVE
  To evaluate the role of antibiotic susceptibility for the treatment outcome of proton pump inhibitor-dependent and independent Helicobacter pylori eradication regimens.
  
  
  METHODS
  In a placebo-controlled clinical study of peptic ulcer patients with H. pylori infection, patients were randomized to receive lansoprazole, clarithromycin and tinidazole twice-daily, clarithromycin and tinidazole once-daily with lansoprazole or with placebo. Helicobacter pylori status was assessed by culture and antibiotic susceptibility by E-test minimal inhibitory concentration (MIC) in 205 clinical isolates.
  
  
  RESULTS
  Primary resistance to clarithromycin and metronidazole was 1 and 76%, respectively. In metronidazole susceptible strains eradication rates were similar at > 90% for all treatment groups (P = 0.49). With low-level metronidazole resistance (4 microg/mL < MIC < 256 microg/mL), eradication rates were similar at >75% (P = 0.80). The major difference was found at high-level metronidazole resistance (MIC >or= 256 microg/mL) with 95%, 58% and 21% eradication in the lansoprazole, clarithromycin and tinidazole twice-daily, lansoprazole, clarithromycin and tinidazole once-daily and placebo, clarithromycin and tinidazole once-daily groups, respectively (P < 0.001).
  
  
  CONCLUSIONS
  In the absence of antibiotic resistance, a once-daily therapy of only clarithromycin and tinidazole can achieve a high rate of H. pylori eradication. Such a combination could offer a simpler and cheaper treatment option for developing countries. The standard, twice-daily proton pump inhibitor-based triple therapy was shown to be efficient in H. pylori eradication even in the presence of high-level metronidazole resistance.
authors.affiliation: Department of Medicine, Unit of Infectious Diseases, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden. wheeldon@tiscali.se
authors.forename: T-U
authors.initials: TU
authors.lastname: Wheeldon
authors.forename: M
authors.initials: M
authors.lastname: Granström
authors.forename: T T H
authors.initials: TT
authors.lastname: Hoang
authors.forename: D C
authors.initials: DC
authors.lastname: Phuncarg
authors.forename: L E
authors.initials: LE
authors.lastname: Nilsson
authors.forename: M
authors.initials: M
authors.lastname: Sörberg
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D017291:Clarithromycin / Q000627:therapeutic use; D004334:Drug Administration Schedule; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D064747:Lansoprazole; D008795:Metronidazole / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010437:Peptic Ulcer / Q000382:microbiology; D054328:Proton Pump Inhibitors; D014011:Tinidazole / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D014011:Tinidazole; D064747:Lansoprazole; D008795:Metronidazole; D017291:Clarithromycin; D009853:Omeprazole