Helicobacter pylori infection

Helicobacter pylori is a gram-negative bacteria that colonizes the stomach. Infection most commonly occurs in childhood and persists for life if left untreated. H. pylori infection is often asymptomatic but may cause dyspepsia and is associated with chronic gastritis, gastric and duodenal peptic ulcer disease (PUD), gastric cancer, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Diagnosis is confirmed using noninvasive tests (e.g., urea breath test) and/or tests on gastric biopsy samples obtained via EGD (e.g., rapid urease test). To optimize sensitivity and specificity, PPIs and antibiotics should be withheld before performing most diagnostic tests. All patients who test positive should be treated with a combination of acid blockers (PPIs or vonoprazan) and antibiotics to eradicate the infection, followed by eradication confirmation testing ≥ 4 weeks after completion of treatment.

• Prevalence
  • Overall prevalence in North America: 30–40% ^[1]
  • Prevalence is higher among individuals with East Asian (3.2×) and Hispanic ancestry (2.6×) than other patient groups. ^[2]
  • Children: ♂ = ♀ ^[3]
  • Adults: ♂ > ♀ ^[2][3]
• Age of onset ^[4]
  • Typically in childhood, but infection can occur at any age
  • Untreated infection persists throughout life.

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: H. pylori is a flagellated, gram-negative, S-shaped, microaerophile bacteria. ^[4]
• Routes of transmission ^[4]
  • Fecal-oral (most likely route)
  • Contaminated water
  • Person-to-person within families

• Acute Infection ^[4]
  • Often asymptomatic
  • Mild to moderate dyspepsia and/or nonspecific abdominal symptoms
• Chronic infection ^[4]
  • Children: often asymptomatic; complications are rare.
  • Adults: symptoms secondary to complications of H. pylori infection, e.g., PUD

General principles

• Prior to testing, withhold medications that can interfere with test results (whenever possible).
  • PPIs for 1–2 weeks ^[3][5]
  • Antibiotics and/or bismuth for ≥ 4 weeks ^[5]
• Choose a noninvasive test (e.g., urea breath test) if there are no indications for EGD.

PPIs should be discontinued 1–2 weeks prior to most H. pylori testing modalities to minimize rates of false-negative results. However, some types of testing, e.g., histology, are not affected by recent PPI treatment. ^[3]

Indications for testing ^[1]

• GI conditions
  • PUD: active disease or a history of disease without prior eradication
  • Uninvestigated dyspepsia: See “Approach to dyspepsia” for details.
  • Early gastric malignancy: e.g., MALT lymphoma
  • Functional dyspepsia
  • History of or high risk for gastric cancer, e.g., individuals with certain endogenous risk factors for gastric cancer
• Other
  • Before starting long-term treatment with low-dose aspirin
  • Long-term use of NSAIDs
  • Unexplained iron deficiency anemia
  • Idiopathic thrombocytopenic purpura
  • Adults who share a household with individuals with H. pylori

Tests

Initial tests

• Noninvasive: Order one of the following if EGD is not indicated. ^[6]
  • Urea breath test: The labeled carbon isotope in a breath sample is quantified.
  • H. pylori stool antigen test: detects H. pylori antigens via an enzyme immunoassay ^[7]
• Invasive: Order one or both of the following tests (performed on a gastric biopsy sample) for patients with indications for EGD. ^[3]
  • Histology (gold standard)
    • Staining and direct microscopic identification
    • Typical microscopic appearance of H. pylori: curved, gram-negative rods with multiple flagella
    • Sensitivity and specificity are not affected by recent PPI treatment.
  • Rapid urease test: detects the amount of ammonia produced by H. pylori during urea hydrolysis

Urea breath test or H. pylori stool antigen test can be used for the initial diagnosis of infection and/or confirmation of eradication.

Do not order an EGD solely to diagnose H. pylori infection.

Other tests ^[3]

The following studies are not widely used and should be ordered in consultation with a GI specialist.

• Serum IgG antibodies against H. pylori
  • Sensitivity and specificity are not affected by recent PPI treatment.
  • Antibodies may still be detected after eradication.
  • Poor positive predictive value if the prevalence of infection is less than approx. 20% ^[7]
• PCR
  • Sensitive and specific, but ordered infrequently because of the high cost
  • May be performed on gastric biopsy, saliva, or stool samples
• Culture and sensitivity testing: useful if antibiotic resistance is suspected

• Differential diagnoses of dyspepsia
• Differential diagnosis of gastric and duodenal ulcers

The differential diagnoses listed here are not exhaustive.

General principles ^[1]

• All patients who test positive for H. pylori infection should be offered H. pylori eradication therapy.
• Recommended regimen: optimized bismuth quadruple therapy
• Consider antibiotic sensitivity testing if results will guide treatment decisions, e.g., in patients with:
  • Penicillin allergy
  • Previous treatment with macrolides or quinolones (for any reason)
  • Previous treatment of H. pylori infection

Initial pharmacotherapy ^[1]

• Optimized bismuth quadruple therapy: 10–14 days (preferred)
  • PPI at standard dose twice daily (e.g., omeprazole ) ^[1]
  • PLUS bismuth (e.g., bismuth subcitrate or bismuth subsalicylate ) ^[1]
  • PLUS tetracycline ^[1]
  • PLUS metronidazole ^[1]
• Rifabutin triple therapy: 14 days ^[1]
  • Rifabutin ^[1]
  • PLUS omeprazole ^[1]
  • PLUS amoxicillin ^[1]
• Potassium-competitive acid blocker therapy (PCAB therapy): 14 days
  • PCAB dual therapy: vonoprazan PLUS amoxicillin ^[1]
  • PCAB triple therapy: vonoprazan PLUS clarithromycin PLUS amoxicillin ^[1]

Bismuth binds to the affected mucosa, providing physical protection from acids, and stimulates gastric HCO3- secretion, which helps to restore the mucosal pH gradient and is hence used to treat peptic ulcers and H. pylori infection (as a part of Bismuth quadruple therapy).

Treatment of persistent infection ^[1]

• Prescribe a salvage regimen with different antibiotics than those used as first-line therapy.
• Preferred: optimized bismuth quadruple therapy for 14 days for patients who have not received it before ^[1]
• Alternatives (all for 14 days)
  • Rifabutin triple therapy
  • Levofloxacin triple therapy: consider for levofloxacin-sensitive H. pylori strains
    • PPI at standard dose ^[1]
    • PLUS levofloxacin ^[1]
    • PLUS amoxicillin OR metronidazole ^[1]
  • PPI clarithromycin triple therapy: consider for clarithromycin-sensitive H. pylori strains ^[1]
    • PPIs at standard or double dose twice daily (e.g., omeprazole ) ^[3]
    • PLUS clarithromycin ^[3]
    • PLUS amoxicillin OR metronidazole ^[3]
  • PCAB triple therapy: Consider for clarithromycin-sensitive H. pylori strains. ^[1]
• Perform antibiotic sensitivity testing if regimens containing clarithromycin or levofloxacin are considered.
• Refer patients with unconfirmed penicillin allergy for allergy testing, e.g., graded challenge testing.
• Refer to a GI specialist for guidance.

Do not prescribe regimens containing clarithromycin or levofloxacin unless sensitivity has been proven. ^[1]

H. pylori infection is associated with an increased risk of several conditions, e.g.:

• PUD
• Dyspepsia
• Chronic gastritis
• Gastric cancer
• MALT lymphoma
• Iron deficiency anemia

We list the most important complications. The selection is not exhaustive.

Eradication confirmation testing ^[1]

• Indication: : all patients post H. pylori eradication therapy
• Timing
  • Hold PPIs for 1–2 weeks before testing. ^[1]
  • Test ≥ 4 weeks after completion of treatment. ^[1]
• Modalities
  • Urea breath testing
  • Stool antigen assay
  • Endoscopic biopsy samples with rapid urea testing (only if endoscopy is indicated for other reasons)