H. pylori is a spiral-shaped, gram-negative organism that has adapted to thrive in acid. In developing countries, it commonly causes chronic infections and is usually acquired during childhood. In the US, infection is less common among children but increases with age: by age 60, about 50% of people are infected. Infection is most common among blacks, Hispanics, and Asians.
The organism has been cultured from stool, saliva, and dental plaque, which suggests oral-oral or fecal-oral transmission. Infections tend to cluster in families and in residents of custodial institutions. Nurses and gastroenterologists seem to be at high risk because bacteria can be transmitted by improperly disinfected endoscopes.
Effects of H. pylori infection vary depending on the location within the stomach.
Antral-predominant infection results in increased gastrin production, probably via local impairment of somatostatin release. Resultant hypersecretion of acid predisposes to prepyloric and duodenal ulcer.
Body-predominant infection leads to gastric atrophy and decreased acid production, possibly via increased local production of interleukin-1 beta. Patients with body-predominant infection are predisposed to gastric ulcer and gastric adenocarcinoma.
Some patients have mixed infection of both antrum and body with varying clinical effects. Many patients with H. pylori infection have no noticeable clinical effects.
Ammonia produced by H. pylori enables the organism to survive in the acidic environment of the stomach and may erode the mucus barrier. Cytotoxins and mucolytic enzymes (eg, bacterial protease, lipase) produced by H. pylori may play a role in mucosal damage and subsequent ulcerogenesis.
Infected people are 3 to 6 times more likely to develop stomach cancer. H. pylori infection is associated with intestinal-type adenocarcinoma of the gastric body and antrum but not cancer of the gastric cardia. Other associated cancers include gastric lymphoma and mucosa-associated lymphoid tissue (MALT) lymphoma, a monoclonally restricted B-cell tumor.
Screening of asymptomatic patients is not warranted. Tests are done during evaluation for peptic ulcer and gastritis. Posttreatment testing is typically done to confirm eradication of the organism.
Laboratory and office-based serologic assays for antibodies to H. pylori have a sensitivity and specificity of > 85% and previously were considered the noninvasive tests of choice for initial documentation of H. pylori infection. However, as the prevalence of infection has declined, the percentage of false-positive results with serologic assays has increased significantly, making these tests too unreliable in most countries and regions. As a result, urea breath testing and stool antigen testing are preferred for initial diagnosis. Qualitative assays remain positive for up to 3 years after successful treatment and because quantitative antibody levels do not decline significantly for 6 to 12 months after treatment, serologic assays are not usually used to assess cure.
Urea breath tests use an oral dose of 13C- or 14C-labeled urea. In an infected patient, the organism metabolizes the urea and liberates labeled CO2, which is exhaled and can be quantified in breath samples taken 20 to 30 minutes after ingestion of the urea. Sensitivity and specificity are > 95%. Urea breath tests are well suited for confirming eradication of the organism after therapy. False-negative results are possible with recent antibiotic use or concomitant proton pump inhibitor therapy; therefore, follow-up testing should be delayed ≥ 4 weeks after antibiotic therapy and 1 week after proton pump inhibitor therapy. H2 blockers do not affect the test.
Stool antigen assays have a sensitivity and specificity similar to that of urea breath tests, particularly for initial diagnosis; an office-based stool test is under development.
Endoscopy is used to obtain mucosal biopsy samples for a rapid urease test (RUT) or histologic staining. Bacterial culture is of limited use because of the fastidious nature of the organism. Endoscopy is not recommended solely for diagnosis of H. pylori; noninvasive tests are preferred unless endoscopy is indicated for other reasons.
The RUT, in which presence of bacterial urease in the biopsy sample causes a color change on a special medium, is the diagnostic method of choice on tissue samples. Histologic staining of biopsy samples should be done for patients with negative RUT results but suspicious clinical findings, recent antibiotic use, or treatment with proton pump inhibitors. RUT and histologic staining each have a sensitivity and specificity of > 90%.
(See also the American College of Gastroenterology’s guidelines for the treatment of Helicobacter pylori infection.)
Patients with complications (eg, ulcer, cancer) should have the organism eradicated. Eradication of H. pylori can even cure some cases of MALT lymphoma (but not other infection-related cancers). Treatment of asymptomatic infection has been controversial, but the recognition of the role of H. pylori in cancer has led to a recommendation for treatment. Vaccines, both preventive and therapeutic (ie, as an adjunct to treatment of infected patients), are under development.
H. pylori eradication requires multidrug therapy, typically antibiotics plus acid suppressants (1). Proton pump inhibitors suppress H. pylori, and the increased gastric pH accompanying their use can enhance tissue concentration and efficacy of antimicrobials, creating a hostile environment for H. pylori.
Quadruple therapy is the best initial therapy in areas where the clarithromycin resistance rate is > 15%, as is the case in many parts of the developed world. In quadruple therapy, the following oral drugs are given for 14 days (2):
A proton pump inhibitor (lansoprazole 30 mg 2 times a day, omeprazole 20 mg 2 times a day, pantoprazole 40 mg 2 times a day, rabeprazole 20 mg 2 times a day, or esomeprazole 40 mg once a day)
Bismuth subsalicylate (524 mg 4 times a day)
Metronidazole 250 mg 4 times a day
Tetracycline 500 mg 4 times a day
Triple therapy was the most frequently prescribed regimen for H. pylori infection. The following oral drugs are given for 10 to 14 days:
However, in many regions of the world, the rate of clarithromycin resistance has been increasing and failure of triple therapy is increasingly likely. Thus, this regimen is not recommended for initial therapy unless ≥ 85% of local strains of H. pylori are known to be susceptible or the regimen is known to still be clinically effective in the local area.
For multidrug-resistance strains of H. pylori, triple therapy with rifabutin appears to be effective (3).
Infected patients with duodenal or gastric ulcer require continuation of the acid suppression for at least 4 weeks. Eradication may be confirmed by a urea breath test, stool antigen test, or upper endoscopy done ≥ 4 weeks after completion of therapy. Confirmation of eradication is reasonable in all treated patients but is mandatory in patients who have serious manifestations of H. pylori infection (eg, bleeding ulcer). Recurrent bleeding ulcer is likely if the infection is not eradicated.
Treatment is repeated if H. pylori is not eradicated. If two courses are unsuccessful, some authorities recommend endoscopy to obtain cultures for sensitivity testing.
1. Yang JC, Lin CJ, Wang HL, et al: High-dose dual therapy is superior to standard first-line or rescue therapy for Helicobacter pylori infection. Clin Gastroenterol Hepatol 13(5):895–905.e5, 2015. doi: 10.1016/j.cgh.2014.10.036.
2. Fallone CA, Chiba N, van Zanten SV, et al: The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology 151(1):51–69, 2016. doi: 10.1053/j.gastro.2016.04.006.
3. Fiorini G, Zullo A, Vakil N, et al: Rifabutin triple therapy is effective in patients with multidrug-resistant strains of Helicobacter pylori. J Clin Gastroenterol 52(2):137–140, 2018. doi: 10.1097/MCG.0000000000000540.
H. pylori is a gram-negative organism that is highly adapted to an acid environment and often infects the stomach; incidence of infection increases with age—by age 60, about 50% of people are infected.
Infection predisposes to gastric, prepyloric, and duodenal ulcers and increases risk of gastric adenocarcinoma and lymphoma.
Make initial diagnosis with a urea breath test or stool antigen assay; if endoscopy is being done for other reasons, analyze biopsy samples using a rapid urease test or histologic staining.
Give treatment to eradicate the organism in patients with complications (eg, ulcer, cancer); a typical regimen includes quadruple therapy in areas that have resistance rates to clarithromycin of > 15% or a proton pump inhibitor plus two antibiotics (eg, clarithromycin plus either amoxicillin or metronidazole).
Confirm cure using a urea breath test, stool antigen test, or upper endoscopy.