However, a multi-drug regimen and an adequate length of treatment are required for eradication. Because antimicrobial resistance and incomplete treatment are major reasons for treatment failure,16,17 convenience and tolerability become important considerations in choosing a treatment plan.
Effective H pylori treatment regimens include a combination of two antibiotics and acid suppression therapy, with or without a bismuth compound, taken for 10 to 14 days. Choosing a combination that can be taken in two daily doses may be easier for patients, although this option is also more costly.Table 3 provides a practical list of selected effective drug combinations used for treating H pylori infection. Triple therapies with reported eradication rates approaching 90% or more are included, though resistant strains may continue to emerge. Single and dual therapies, though FDA-approved for treatment of H pylori, have unacceptably low cure rates and are not recommended. PPI quadruple therapy or a regimen including furazolidone (a monoamine oxidase inhibitor) may serve as second-line treatment for eradication of initial failures and in case of metronidazole resistance.18,19 Studies using ranitidine bismuth citrate in place of PPIs have also shown comparable results.
Patient education regarding the need for effective eradication therapy and to encourage adherence to the drug regimen is critical. Patients should have adequate follow-up, since further diagnostic testing may be needed to ensure eradication of the H pylori organism, particularly in the case of treatment failure or relapse. Because eradication usually cures peptic ulcer disease, chronic acid suppression therapy should not be needed in most patients who have cleared the H pylori infection and who are not taking NSAIDs. Among primary care patients with a history of peptic ulcer disease taking chronic acid suppressive therapy, 78% of those treated for H pylori were able to discontinue their therapy.21
Persistent or recurrent ulcers in patients treated for H pylori are strongly associated with persistent or recurrent infection.22 Because symptom relief is not always correlated with eradication, testing for cure following eradication therapy should be considered, particularly in high-risk patients, such as those with a history of bleeding or perforation.13 However, no randomized studies have been done to assess the outcomes associated with the decision to test for cure. If desired, noninvasive tests (eg stool antigen test or urea breath test) may be used for patients who become symptom-free following eradication therapy or for patients with persistent symptoms and a previously documented duodenal ulcer. Acid suppressive therapy with a PPI can result in false negative results, so this should be withheld for at least 2 weeks prior to testing for persistent infection.23 Because of the risk of cancer associated with gastric ulcers, endoscopic documentation of gastric ulcer healing might be preferable to noninvasive testing, particularly in high-risk patients. In either case, patients with persistent or recurrent symptoms following eradication should have endoscopy to document ulcer healing and to obtain biopsies if necessary.
Nonulcer Dyspepsia
The pathophysiology of nonulcer dyspepsia (NUD) is not definitively known, though factors implicated include gastric acid secretion, gastro-duodenal dysmotility, visceral hypersensitivity, stress, and psychological factors.24 A relationship with H pylori has not been established, though there is some evidence of an association.25
Studies of drug treatments for NUD are limited by small samples, short duration of follow-up and the use of unvalidated outcome measures.26 A recent meta-analysis found no significant benefit from the use of antacids or sucralfate for NUD, defined as dyspeptic symptoms with negative endoscopic or barium studies, excluding other organic (eg pancreato-biliary disease, oesophagitis) and drug-induced (NSAIDs) disease. The same study reported statistically significant benefits with the prokinetic drug cisapride, but there was evidence of a publication bias in these comparisons, making interpretation difficult (“positive” studies were more likely to be published than “negative” trials). Cisapride was also recently taken off the market, so is no longer available as a treatment option. No placebo-controlled studies of metoclopramide were identified in this systematic review.
Antisecretory treatments were more effective than placebo in the treatment of NUD, with a number needed to treat of 6 for H2-RAs and 11 for PPIs (ie, for every 11 patients who received a PPI instead of placebo, one benefited).24 Thus, PPIs were actually less effective than H2-RAs in this meta-analysis of placebo-controlled trials. Long-term use of antisecretory therapy may be associated with hypergastrinemia, increased gastrointestinal bacterial counts, and altered absorption of nutrients, though the clinical significance of this is unclear.27 For patients who do not respond to acid-suppressive therapy it might be necessary to entertain alternative diagnoses, and if no explanation for the symptoms can be identified, consider counseling or pain management strategies to help the patient cope with the discomfort. Studies of the use of antidepressants, though small and of questionable quality, consistently show improvement in symptoms of patients with functional gastrointestinal disorders, including NUD and irritable bowel syndrome.28 Treatment recommendations for NUD are shown inTable 4.