Resident Editor: Nadine Pardee, MD

Faculty Editor: Aparajita Singh, MD, MPH

BOTTOM LINE ✔ H. pylori infection is often  asymptomatic but may lead to PUD, gastritis, duodenitis and increased risk of gastric malignancy ✔ All patients with a positive test of active infection should be offered treatment to prevent these complications ✔ Reinfection is unusual, but ~20% of patients fail initial treatment due to resistance or non-adherence. Testing for eradication recommended for all patients.

Background

• H. pylori is a Gram-negative bacterium that infects the stomach and/or duodenum
• H. pylori is the most common chronic bacterial infection in humans.  Estimated Prevalence: 70% in developing countries and 30%-40% in the US.
• Transmission:  Unknown. Believed to be fecal oral or possibly oral-oral; most infections acquired in childhood
• High risk populations: older age, non-white race, foreign born, low income, crowding, patients with PUD

Signs and Symptoms

• 80% of cases are asymptomatic. Can lead to PUD (1-10%), gastric cancer (0.1-3%), or mucosa-associated lymphoid tissue (MALT) lymphoma (<0.01%)

Evaluation

• History: Dyspepsia, abdominal pain, hematochezia, melena, hematemesis, weight loss. Ask about recent antibiotic exposure to help guide regimen.
• Physical: Normal exam, epigastria tenderness, pallor
• Non-Invasive tests:  

1) Serologic test (85-95% sensitive, 75%-95% specific)

- Can remain positive for long term, therefore not helpful in differentiating from active infection vs. old infection.

- Titers may remain elevated after eradication, not helpful for testing of eradication

- If local prevalence is <20%, as in much of the U.S., a positive result is more likely a false positive than a true infection

- Accuracy not effected by PPI use

2) Urease breath test (88-95% sensitive, >95% specific)

- Useful for testing for active infection or confirming eradication after therapy.

- Patient must fast for 6 hours prior to test

- Stop PPI 1-2 weeks prior to testing; PPI therapy may produce a false negative result

- Active upper GI bleed reduces sensitivity but not specificity of urease breath testing

3) Stool antigen test (94% sensitive, 97% specific)

- Useful for testing for active infection or confirming eradication after therapy

- Stop PPI 1-2 weeks prior to testing; PPI therapy may produce a false negative result

- Active upper GI bleed reduces specificity but not sensitivity of stool antigen testing

• Endoscopic tests:

Endoscopy is not indicated solely for the testing of H pylori. Note that a negative biopsy does not rule out H. pylori in the setting of upper GI bleed, and a non-invasive test should be performed if biopsy is negative and clinical suspicion is high.

1) Biopsy/Histology: (>95% sensitive and specific)

- Assessment by pathologist with Giemsa or immune stains

- Sensitivity may be decreased in acute GI bleeding and those on PPI therapy

2) Urease testing of biopsy specimen: (>95% sensitive and specific)

- Rapid and less expensive than histology; used if no recent exposure to H. pylori treatment or PPI, howevermay not be widely available.

3) Culture (relatively insensitive but 100% specific)

- Not widely available. Rarely done for antibiotic sensitivities for resistant organism for failed therapies

• PPI/H2 blocker use can cause false negative results with above non-serologic tests, consider holding for at least two weeks before test.

Indications for testing for H. Pylori
Strong recommendation, high quality of evidence	Conditional recommendations, low quality of evidence	Insufficient evidence
Active peptic ulcer disease (PUD)	Dyspepsia in pts <60 without alarm features	GERD without dyspepsia
Past history of PUD not previously treated for H.  pylori	Prior to initiation of long term NSAID therapy, including ASA 81 mg	Patients already taking NSAIDs
Gastric cancer/ MALT lymphoma	Unexplained iron deficiency	Family history of gastric cancer
	Chronic immune thrombocytopenia	Patients with lymphocytic gastritis, hyperplastic gastric polyps, or hyperemesis gravidarum

Treatment

• Standard initial treatment options:  Triple therapy for 14 days: Clarithromycin 500 mg BID, Amoxicillin 1 gm BID, plus PPI* BID.
  • Only select if no previous to exposure clarithromycin or <15% prevalence of resistance to clarithromycin. Limited information is available regarding resistance patterns in the U.S. For this reason many guidelines recommend choosing quadruple therapy as initial treatment.
  • Eradication rates in the U.S. <80%
  • If penicillin allergic: switch amoxicillin to metronidazole 500 mg TID
• Quadruple therapy for 10-14 days: Metronidazole (250 QID or 500 TID-QID), Tetracycline 500mg  QID,  Bismuth  subsalicylate 525 mg QID, and PPI* BID  (Tetracycline is often not available, can use doxycycline 100 mg  BID instead; Pylera is a QID combination product of bismuth, tetracycline and metronidazole that is FDA-approved)
  • Eradication rates in the U.S. ~90%
• Concomitant therapy for 10-14 days: Clarithromycin 500 mg BID, Amoxicillin 1 gm BID, Metronidazole or Tinidazole 500 mg BID, plus PPI* BID
  • No eradication studies in North America, but 90% outside of the U.S.
• *PPI: Once daily option: Esomeprazole 40 mg once daily. BID options: Omeprazole 20 mg, Rabeprazole 20 mg, Pantoprazole 40 mg, or Lansoprazole 30 mg.

● Alternative therapies: Sequential therapy, hybrid therapy, and levofloxacin-based therapies are only conditionally recommended as first line therapies in North America due to regimen complexity and resistance rates

● Probiotics: Some studies suggest improved cure rates and decreased side effects with concomitant probiotics, but evidence is insufficient to recommend this practice.                                  

• Testing for Eradication:
  • Reinfection is unusual, but ~20% of patients fail initial treatment due to resistance or non-adherence. Testing for eradication recommended for all patients
  • Re-test for H. pylori with breath test or fecal antigen test 4 weeks after treatment to confirm eradication (PPI can interfere with these tests, Hold PPI for 1- 2 weeks).
  • Retreatment requires salvage therapies, avoiding antibiotics that were previously used
    • Bismuth quadruple therapy salvage for 14 days: Metronidazole 250 mg QID, Tetracycline 500mg  QID,  Bismuth  subsalicylate 525 mg QID, and PPI BID 
      • If first line was clarithromycin containing regiment
    • Levofloxacin-based salvage for 14 days: Levofloxacin 500 mg QD, amoxicillin 1 g BID, plus PPI BID
      • Regardless of first line therapy
    • Concomitant clarithromycin-based salvage for 10-14 days: Clarithromycin 500 mg BID, Amoxicillin 1 gm BID, Metronidazole 500 mg BID, plus PPI* BID
      • If first line was bismuth quadruple therapy
• If persistent infection after two courses of treatment, endoscopy with biopsy for culture and sensitivity is indicated.

When to refer

• Consider referral to Gastroenterology for treatment failure after a second course of treatment, or if there is clinical concern for PUD or malignancy (weight loss, dysphagia, iron deficiency anemia, age > 60)
• Consider referral for penicillin allergy testing if penicillin-allergic patient failed first line therapy

References

Chey WD, Leontiadis GI, Howden CW, and Moss SF.  ACG Clinical Guideline: Treatment of Helicobacter pylori Infection Am J Gastroenterol. February 2017;112(2):212–239

Fashner, J and Gitu, AC. Diagnosis and Treatment of Peptic Ulcer Disease and H. Pylori Infection. Am Fam Physician. 2015 Feb 15; 91(4)236-242.

Kavitt RT, Cifu AS. Management of Helicobacter pylori Infection. JAMA Clinical Guidelines Synopsis. 2017 Vol 317 (15) 1572-1573

McColl KEL. Helicobacter pylori infection. NEJM. 2010. Vol. 362 (17) 1597-1604.

Sachs G, Scott DR, Wen Y. Gastric Infection by Helicobacter pylori. Current Gastroenterology Reports. 2011. Vol. 13(6)540-546.