Testing for H. pylori: Which Patients, Which Test, How to Treat?

Margaret A. Fitzgerald, DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC, FNAP

Helicobacter pylori is a gram-negative bacterium that inhabits the gastric mucous layer and the epithelial lining of the stomach. Within developed countries, the prevalence of H. pylori infection varies by region based on differences in socioeconomic living conditions, with higher prevalence associated with living in close quarters, and food and water contamination.1 Infection with H. pylori leads to chronic inflammation of the gastric mucosa as well as acid-related damage to the duodenal mucosa, and is linked to the development of chronic gastritis, peptic ulcer disease, gastric cancer, and dyspeptic symptoms.2 Because there is a clear association between infection and several gastrointestinal conditions, current guidelines recommend a strategy that includes testing for infection in select patients, treating infected persons to eradicate the infection, and, in some cases, retesting to confirm eradication.

Routine testing for H. pylori infection is considered inappropriate, because most patients (approximately 80% to 85%)2,3 who are infected remain asymptomatic and do not develop clinically significant gastrointestinal disease related to the infection. Guidelines from the American College of Gastro enterology (ACG) and the American Gastroenterological Association (AGA) provide recommendations on which tests to use to identify infected patients and which patients should undergo H. pylori testing and eradication treatment.4-7

Which tests should be used for H. pylori testing?

Tests for H. pylori infection are categorized based on whether they entail invasive (endoscopic) or noninvasive (nonendoscopic) methods for collecting specimens for testing. Noninvasive testing is appropriate in most situations, particularly for testing in patients with uninvestigated dyspepsia in the primary care setting.1,4 Biopsy-based endoscopic tests are generally reserved for patients who require evaluation with upper endoscopy.

There are three types of noninvasive tests: serologic detection of antibodies to H. pylori, urea breath tests (UBTs), and fecal antigen test (FAT). Notably, serology testing is not recommended by the ACG because it has poor predictive value in populations with a low prevalence of H. pylori infection and is unable to distinguish between active infection and prior exposure to H. pylori, as antibodies remain detectable for years following eradication of infection.4 Many laboratories are discontinuing H. pylori serology testing because of the assays’ poor performance characteristics and because multiple insurance providers no longer reimburse for the test due its limited clinical usefulness.3 As alternatives to serologic testing, both the ACG and the AGA recommend the UBT or the FAT.4,5

Urea Breath Test
H. pylori uses the enzyme urease to convert urea in the gastric juice to alkaline ammonia and carbon dioxide, a property that allows the organism to survive in the stomach’s acidic environment.2 The stomach normally does not have urease activity, so detecting activity of this enzyme indicates the presence of H. pylori.1 The UBT involves drinking urea that is labeled with the nonradioactive isotope carbon-13. If H. pylori is present, its urease will split the carbon-13-labeled urea to produce ammonia and carbon-13-labeled carbon dioxide, which is expired in the breath and measured in a postingestion breath sample.

UBT offers the advantages of measuring active infection and having a sensitivity and specificity of 95%.2 In addition, the test can be used for both initial diagnosis and for confirming eradication following therapy; follow-up testing to confirm eradication should be performed at least 4 weeks after completion of therapy. The UBT is approved by the Food and Drug Administration for patients aged 3 years and older.3 The sensitivity of tests for active H. pylori infection can be impaired by the recent use of proton pump inhibitors (PPIs), H2-receptor antagonists (HRAs), bismuth, or antibiotics. As such, the UBT should be administered after the patient has discontinued PPIs for 2 weeks, HRAs for 24 hours, and antibiotics and bismuth for 4 weeks.1,2

Fecal Antigen Test
The FAT identifies H. pylori antigen in a stool sample by enzyme immunoassay with the use of polyclonal or monoclonal antibodies. As with the UBT, a positive result provides definitive evidence of active infection. The monoclonal-antibody test has a sensitivity and specificity of 95%.2 A potential drawback of the test is patient discomfort with sample collection. Also, patients must discontinue PPIs for 2 weeks, HRAs for 24 hours, and antibiotics for 4 weeks before the FAT is administered.2

Who should be tested for H. pylori?

Clinicians should test for H. pylori only when they intend to offer treatment for positive results. According to ACG guidelines, the following are established indications for diagnosis and treatment of H. pylori infection:

  • Active peptic ulcer disease (gastric or duodenal ulcer) or confirmed history of peptic ulcer disease (not previously treated for H. pylori infection)
  • Gastric mucosa-associated lymphoid tissue (MALT) lymphoma (low-grade)
  • After endoscopic resection of early gastric cancer
  • Uninvestigated dyspepsia (depending upon H. pylori prevalence)4,6

Also, the ACG’s most recent H. pylori treatment guideline6 extends the list of potential indications for testing to include patients initiating long-term non steroidal anti-inflammatory drug therapy, those starting prophylactic low-dose aspirin, those with unexplained iron deficiency anemia despite an appropriate evaluation, and adults with idiopathic thrombocytopenic purpura. The ACG notes, however, that the quality of the evidence supporting these recommendations varies from low to moderate, and therefore decisions about testing in individual patients should be influenced by the clinician’s judgment and consideration of the patient’s overall condition.

With respect to patients presenting with symptoms of gastroesophageal reflux disease (GERD; heartburn,regurgitation, chest pain, nausea, and chronic cough/ hoarseness), current ACG guidelines note that GERD is not an indication for testing a patient for H. pylori unless the patient also has a history of peptic ulcer disease or dyspeptic symptoms.6

Table 1. ALARMS findings

Anemia (iron deficiency)

Loss of weight (involuntary)

Anorexia (persistent)

Recent onset of progressive symptoms

Melena (tarry/bloody stools) or hematemesis (vomiting bright red blood)

Swallowing difficulty (dysphagia [difficulty swallowing], odynophagia [painful swallowing])

For primary care clinicians, decisions regarding testing for H. pylori most often arise when a patient presents with dyspeptic symptoms. Dyspepsia is a common problem, with a prevalence of approximately 10% in adults.8 Uninvestigated dyspepsia refers to symptoms of dyspepsia in patients who present to primary care and who have not undergone endoscopic evaluation for their symptoms. The test-and-treat strategy (noninvasive testing with UBT or FAT followed by treatment with a recommended oral regimen for those with a positive result) is recommended for patients with uninvestigated dyspepsia who are younger than 60 years and who do not have ALARMS findings (Table 1).6,7 Patients who meet these criteria should be tested for H. pylori by means of either UBT or FAT. Upper endoscopy should be considered if ALARMS findings are present with a GERD diagnosis. For patients with dyspepsia who are aged 60 and older, the ACG suggests endoscopic evaluation to exclude upper gastrointestinal neoplasia (conditional recommendation), but does not suggest endoscopy to investigate ALARMS features for dyspepsia patients younger than 60 to exclude upper GI neoplasia (conditional recommendation).7

Patients who test positive for H. pylori infection are offered eradication therapy, which typically includes two antibiotics plus a PPI and/or a bismuth preparation (see Table 2 and section on treatment).

Table 2. Recommended Regimens for First-line Treatment of H. pylori Infection6

Regimen Duration
Clarithromycin Triple Therapy* 14 days
PPI (standard or double dose) orally twice daily
Clarithromycin 500 mg orally twice daily
Amoxicillin 1000 mg orally twice daily
PPI orally twice daily*
Clarithromycin 500 mg orally twice daily
Metronidazole 500 mg orally three times daily
Bismuth Quadruple Therapy 10 to 14 days
Bismuth subcitrate (120-300 mg) or subsalicylate (300 mg) orally four times daily
PPI (standard dose) orally twice daily
Metronidazole 250-500 mg orally three or four times daily
Tetracycline 500 mg orally four times daily
Nonbismuth-Based Quadruple Therapy 10 to 14 days
PPI (standard dose) orally twice daily
Clarithromycin 500 mg orally twice daily
Amoxicillin 1000 mg orally twice daily
Nitroimidazole (tinidazole or metronidazole) 500 mg orally twice daily
Omeprazole, magnesium, rifabutin, amoxicillin delayed-release capsules (Talicia)10 14 days
Four capsules taken three times daily (omeprazole 120 mg, rifabutin 150 mg, amoxicillin 3 g)
*Recommended in regions where H. pylori clarithromycin resistance is known to be <15% and in patients with no history of macrolide exposure.
†Doses of proton pump inhibitors (PPIs) are: esomeprazole 20 mg (or 40 mg once daily), lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg, rabeprazole 20 mg.

Other Recommendations

The ACG guidelines highlight several other important areas regarding H. pylori testing and treatment:

  • Nonulcer, or functional, dyspepsia. Functional dyspepsia refers to patients who have unexplained upper abdominal pain or discomfort and normal findings on upper endoscopy.9 A small percentage of patients with functional dyspepsia do benefit from eradication, and the guidelines recommend collecting biopsies of normal-appearing gastric mucosa to test for H. pylori when performing endoscopy in patients with dyspeptic symptoms; patients with positive biopsy results should be treated with H. pylori eradication therapy.6,7
  • Gastroesophageal reflux disease. Because H. pylori reduces gastric acid secretion in some patients, eradication of the bacteria can lead to worsening of reflux symptoms.1 As noted above, current guidelines note that GERD is not an indication for testing a patient for H. pylori, unless the patient also has a history of peptic ulcer disease or dyspeptic symptoms.6 Patients with GERD who test positive should be offered eradication therapy, but clinicians should explain to patients that this treatment is unlikely to improve their GERD symptoms.
  • Populations at higher risk for gastric cancer. Some studies have suggested that eradicating H. pylori can prevent progression of intestinal metaplasia to gastric adenocarcinoma, but overall the evidence is conflicting and currently there is no definitive evidence to support eradication as a chemopreventive strategy in the general population.1,4,6

Omeprazole, magnesium, rifabutin, amoxicillin delayed-release capsules (Talicia) were approved by the FDA in 2019.10 It is the first and only FDA-approved rifabutin-based H. pylori therapy. Because approval occurred after the ACG guidelines were updated in 2017, it does not appear in the list of recommended first-line regimens for H. pylori treatments.10 The use of rifabutin in this medication is an alternative to therapies using clarithromycin, which is associated with high and increasing levels of bacterial resistance and thus decreased efficacy and treatment failure.10 A 2018 review of the prevalence of antibiotic-resistant H. pylori in World Health Organization (WHO) regions found that primary and secondary resistance rates to clarithromycin, metronidazole, and levofloxacin were ≥15% in all WHO regions, except for primary clarithromycin resistance in the Americas and Southeast Asia regions (10%).11

Drug-drug interactions with clarithromycin must also be considered. Clarithromycin is a strong inhibitor of the cyto chrome P450 isoenzyme CYP3A, and may increase the plasma concentration of statins metabolized in this pathway, increasing the risk of interaction with statins.12 Other medications that can interact with clarithromycin include warfarin, carbamazepine, phenytoin, and phenobarbital.


Patients who test positive for H. pylori should be treated with one of the recommended regimens outlined in the ACG guidelines (Table 2).4,6 H. pylori treatment has been complicated by the decline in effectiveness of many regimens because of increasing antibiotic resistance—mainly due to high rates of clarithromycin resistance.9 The WHO labeled H. pylori one of the patho gens that is a high priority for research and development of new antibiotics world wide because of growing resistance to clarithromycin.13

Before selecting an H. pylori treatment regimen, patients should be asked about any previous antibiotic exposure(s) and this information should be taken into consideration when choosing a regimen. In terms of further testing to confirm eradication following therapy, either the UBT or the FAT can be used 4 weeks or longer after completion of therapy.

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12. Ament PW, Bertolino JG, Liszewski JL. Clinically significant drug interactions. Am Fam Physician. 2000;61:1745-54. https://www.aafp.org/afp/2000/0315/p1745.html. Accessed March 26, 2021.
13. World Health Organization. WHO publishes list of bacteria for which new antibiotics are urgently needed. February 27, 2017. https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed. Accessed March 28, 2021.