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Illusions regarding Helicobacter pylori clinical trials and treatment guidelines
  1. David Y Graham
  1. Correspondence to Dr David Y Graham, Department of Medicine, Michael E DeBakey VA Medical Center and Baylor College of Medicine, Houston, Texas, USA; dgraham{at}

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Identification of reliable Helicobacter pylori eradication therapy has proved difficult, in part because brief exposure of H. pylori to commonly used antimicrobials such as macrolides, nitroimidazoles or quinolones often results in resistance (bystander effect). Most treatment studies and meta-analyses contains major flaws preventing generalisability that making reliable treatment recommendations and guidelines an illusion (box 1).

Box 1

Helicobacter pylori treatment illusions

  • Most apparently well done treatment studies and meta-analyses are valid.

  • Studies reporting one regimen as superior to another can generally be believed.

  • Meta-analyses identifying the best H. pylori treatment regimen can generally be believed.

  • Treatment results without susceptibility testing are generally valid.

  • High overall cure rates validate use of successive low cure rate first, second and third-line treatments.

  • Increasing the number of antibiotic to 3 or 4 (eg, concomitant or quintuple therapies) is a rational approach to overcoming resistance.

  • Commercially available regimens have generally been optimised.

Development of H. pylori therapy differs from other infectious diseases. Since the advent of antibiotics, infectious diseases therapy has been susceptibility based, whereas most H. pylori treatment guidelines recommend susceptibility testing only after two empiric therapy failures. Increased penicillin resistance in the 1970s prompted rapid changes in recommendations and the development of antimicrobial surveillance programme to regularly update recommendations thus allowing empirical therapies to remain effective.1 Despite increasing resistance, H. pylori treatment guidelines have continued to recommend increasingly ineffective therapies and most new empiric therapies consist of variations using those same drugs (eg, sequential therapy). Treatment success has focused on comparisons between regimens irrespective of cure rates and without consideration of the antibiotic susceptibility profile of the infection, thus producing illusions of success. For example, sequential therapy consists of 5 days of dual proton pump inhibitor (PPI)–amoxicillin therapy followed by 5 days of PPI–clarithromycin and metronidazole triple therapy (Bazzoli’s triple therapy).2 Interestingly, sequential therapy …

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