Helicobacter Pylori

Aka: Helicobacter Pylori, H. pylori, Helicobacter Pylori Treatment, H. Pylori Management, Non-NSAID Associated Peptic Ulcer, Helidac, Pylera, Campylobacter pylori, Helicobacter-associated gastritis

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II. Epidemiology

  1. Colonizes the gastric mucosa in 50% of world population and 30-40% of U.S. population

III. Pathophysiology: Helicobacter Pylori

  1. Spiral-shaped (helical) Gram Negative Bacteria
  2. Colonizes gastric mucosa or epithelial lining
  3. Acquired in early childhood via fecal-oral transmission

IV. Associated conditions

  1. Dyspepsia
  2. Peptic Ulcer Disease
    1. Duodenal Ulcers: 95% related to H. pylori
    2. Gastric Ulcers: 70-80% related to H. pylori
  3. Stomach Cancer (epithelial or lymphoid)
    1. IARC considers H. pylori a Group I Carcinogen
    2. Mucosa-associated Lymphoid Tissue (MALT)
    3. Gastric adenocarcinoma

V. Symptoms (Asymptomatic in 90% of cases)

  1. See Dyspepsia
  2. See Peptic Ulcer Disease

VI. Differential Diagnosis

  1. See Dyspepsia Causes
  2. See Medication Causes of Dyspepsia

VII. Labs

  1. General
    1. Stop Antibiotics for 4 weeks before Helicobacter Pylori testing
    2. Stop Proton Pump Inhibitors (PPIs) for 2 weeks before Helicobacter Pylori testing
    3. Only Serology and Rapid Urease Test are not affected by Antibiotics and PPIs
  2. Helicobacter pylori Noninvasive Testing
    1. Urea Breath Test (Carbon 13)
      1. Test Sensitivity: 96 to 100%
      2. Test Specificity: 93 to 100%
      3. Likelihood: LR+ 12, LR- 0.05
      4. Ferwana (2015) World J Gastroenterol 21(4): 1305-14 [PubMed]
    2. Helicobacter pylori Stool Antigen (HpSA Monoclonal Antibody test)
      1. Test Sensitivity: 94%
      2. Test Specificity: 97%
      3. Likelihood: LR+ 24, LR- 0.7
      4. Gisbert (2006) Gastroenterol 101(8): 1921-30 [PubMed]
    3. Helicobacter Pylori IgG Serology
      1. Test Sensitivity: 85%
      2. Test Specificity: 79%
      3. Likelihood: LR+ 2.8, LR- 0.2
      4. Does not differentiate current active infection from prior infection
  3. Helicobacter pylori Invasive Testing (upper endoscopy)
    1. Histology (endoscopic biopsy)
      1. Test Sensitivity: 70%
      2. Test Specificity: 90%
      3. Likelihood: LR+ 6.7, LR- 0.23
    2. Rapid Urease Test
      1. Test Sensitivity: 67%
      2. Test Specificity: 93%
      3. Likelihood: LR+ 9.6, LR- 0.31
    3. Helicobacter Pylori Culture (endoscopic biopsy sample)
      1. Test Sensitivity: 45%
      2. Test Specificity: 98%
      3. Likelihood: LR+ 19.6, LR- 0.31
  4. References
    1. Gisbert (2006) Am j Gastroenterol 101(4): 848-63 [PubMed]
    2. Bordin (2021) Diagnostics 11(8): 1458 [PubMed]
    3. Kayali (2018) Acta Biomed 89(8-S): 58-64 [PubMed]

VIII. Management: General

  1. Do not indiscriminately test and treat H. pylori
  2. Resistance is increasing markedly
    1. Metronidazole resistance is very common
      1. Resistance overcome by the following measures
        1. Increase acid suppression
        2. Increase Metronidazole dose
        3. Increase therapy duration
    2. Clarithromycin resistance is growing (8-12%)
      1. Resistance can not be overcome
      2. Do not use protocols with Clarithromycin where H.Pylori resistance rates >15-20%
  3. Benefits of treating H. pylori
    1. Significantly drops ulcer recurrence, rebleeding risk
    2. Improves symptoms in Nonulcer Dyspepsia (variable)
    3. Unclear evidence for gastric Cancer Prevention
    4. No evidence for benefit in GERD
  4. Test for H. pylori before treatment
    1. See Helicobacter pylori Noninvasive Testing
  5. Test 4-6 weeks after treatment if indicated
    1. Indications
      1. Persistant Dyspepsia or other related symptoms
      2. Peptic Ulcer Disease
      3. Mucosal-Associated Lymphoid Tumor (MALT Lymphoma)
      4. Gastric adenocarcinoma
    2. Testing options to confirm H. pylori eradication
      1. H. pylori Stool Antigen (HpSA)
      2. Urea Breath Test
      3. Endoscopic Biopsy for H. pylori
  6. Protocol pearls
    1. Treatment duration: usually 14 days to maximize eradication rates
    2. Use at least 3 agents (do not use 2 agent regimens)
    3. If failed therapy - see resistant cases below
  7. Consider concurrent Probiotic
    1. Add Saccharomyces boulardii and/or Lactobacillus to regimen
    2. Increases eradication rates and decreases Antibiotic Associated Diarrhea
    3. Szajewska (2010) Aliment Pharmacol Ther 32(9): 1069-79 +PMID:21039671 [PubMed]
    4. Zou (2009) Helicobacter 14(5): 97-107 +PMID:19751434 [PubMed]

IX. Protocols: Preferred protocols for adults

  1. Bismuth Quadruple Therapy (up to 98% efficacy)
    1. Background
      1. Gold standard for Helicobacter Pylori due to highest efficacy, lowest resistance rates and lowest cost
      2. Consider if Penicillin allergic or prior treatment for H. pylori with Macrolide (e.g. Clarithromycin)
      3. Compliance is difficult due to four time daily dosing
      4. Bismuth causes Constipation and black discoloration of mouth and stools
    2. Components: Use all four for 14 days (extended use of the Proton Pump Inhibitor)
      1. Proton Pump Inhibitor twice daily for up to 6 weeks
        1. Omeprazole (Prilosec) 20 mg orally twice daily
        2. Lansoprazole (Prevacid) 30 mg orally twice daily
        3. May substitute Ranitidine (Zantac) 300 mg orally daily, but is less ideal
      2. Metronidazole (Flagyl) 500 mg orally four times daily for 14 days (some protocols use 2 or 3 times daily)
        1. May substitute Tinidazole (Tindamax) 500 mg orally twice daily for 14 days
      3. Tetracycline 500 mg orally four times daily for 14 days
        1. No evidence that Doxycycline has equivalent efficacy against Helicobacter Pylori
      4. Bismuth subcitrate (Pepto-Bismol) 262 mg orally four times daily for 14 days
        1. May substitute Bismuth Subsalicylate 535 mg orally four times daily
    3. Combination Packs
      1. Use Omeprazole (or other PPI) with either Helidac or Pylera
        1. Helidac and Pylera each include Metronidazole, Tetracycline and Bismuth
  2. Concomitant Quadruple Therapy (Triple Therapy with Metronidazole)
    1. Background
      1. Replaces the older triple therapy or LAC protocol (Lasoprazole-Amoxicillin-Clarithromycin)
        1. Addition of Metronidazole signifcantly improves efficacy
      2. More expensive than the quadruple therapy (due to Clarithromycin cost)
      3. Patients may prefer this protocol to quadruple therapy
        1. Better tolerated (no bismuth associated Black Tongue, stools, or Constipation)
        2. Better compliance (twice daily instead of four times daily)
    2. Components: Use all four for 14 days (extended use of the Proton Pump Inhibitor)
      1. Proton Pump Inhibitor for up to 6 weeks
        1. Omeprazole (Prilosec) 20 mg orally twice daily
        2. Lansoprazole (Prevacid) 30 mg orally twice daily
      2. Amoxicillin 1000 mg orally twice daily for 14 days
      3. Clarithromycin (Biaxin) 500 mg orally twice daily for 14 days
        1. Do not substitute other Macrolides
        2. Azithromycin and Erythromycin do not have adequate Helicobacter Pylori coverage
      4. Metronidazole (Flagyl) 500 mg orally twice daily for 14 days
        1. May substitute Tinidazole (Tindamax) 500 mg orally twice daily for 14 days
  3. References
    1. Chey (2017) Am J Gastroenterol 112(2):212-239 +PMID:28071659 [PubMed]

X. Protocols: Adults Resistant Cases

  1. General for failed therapy
    1. Step Up to 4-5 agent therapy without Metronidazole
  2. Quadruple therapy
    1. See Quadruple therapy above under adults long
  3. Triple Therapy with Amoxicillin and Rifabutin (Talicia)
    1. Combination capsules of Omeprazole, Amoxil and Rifabutin (Mycobutin)
    2. Four capsules per dose
      1. Each capsule contains Omeprazole 10 mg, Amoxil 250 mg, Rifabutin 12.5 mg
      2. Each total dose contains Omeprazole 40 mg, Amoxil 1000 mg, Rifabutin 50 mg
    3. Four capsules taken three times daily for 14 days
    4. Adverse effects related to Rifabutin (body fluid stained orange, CYP3A4 inducer)
      1. Hormonal Contraception requires backup Contraception for 28 days
    5. References
      1. (2020) Presc Lett 27(5):29
      2. Qasim (2005) Aliment Pharmacol Ther 21:91-6 [PubMed]
  4. Levofloxacin Based Therapy
    1. Do not use if Levofloxacin-based therapy has been used in the past
    2. Take all three agents for 14 days
      1. Proton Pump Inhibitor AND
      2. Amoxicillin 1000 mg orally twice daily AND
      3. Levofloxacin 500 mg orally daily

XI. Protocols: Children

  1. Indications for testing
    1. Suspected Peptic Ulcer Disease (uncommon in children)
    2. Testing and treating is not recommended for functional Abdominal Pain
    3. Wait to test for 2 weeks after last Proton Pump Inhibitor and 4 weeks after last Antibiotic
  2. Protocol
    1. Omeprazole 1 mg/kg/day divided twice daily (max: 20 mg orally twice daily) and
    2. Take the following 3 Antibiotics for 14 days (same as concomitant therapy above)
      1. Amoxicillin 50 mg/kg/day divided twice daily (max: 1000 mg twice daily)
      2. Clarithromycin 15mg/kg/day div bid (max: 500 mg twice daily)
      3. Metronidazole 20 mg/kg/day div bid (Max: 500 mg twice daily)
  3. References
    1. Gold (2000) J Pediatr Gastroenterol Nutr 31:490-7 [PubMed]

XII. Protocols: Pregnancy

  1. Indications for Treatment during pregnancy
    1. Severe symptoms (e.g. refractory Hyperemesis Gravidarum)
    2. If only mild symptoms, consider delaying management until after delivery and Lactation
  2. Protocol in pregnancy
    1. Treat for 7 day course
    2. First Trimester
      1. Lansoprazole (Prevacid) 30 mg orally twice daily AND
      2. Amoxicillin 1000 mg orally twice daily AND
      3. Metronidazole (Flagyl) 500 mg orally twice daily
    3. Second and Third Trimester
      1. Follow first trimester protocol
      2. Clarithromycin (Biaxin) 500 mg orally twice daily may be substituted for Metronidazole

XIII. Management: Consider maintenance antisecretory therapy

  1. Maintenance management: 50% of treatment dose
  2. Indications
    1. Complicated Peptic Ulcer Disease
    2. Elderly or frail

XIV. References

  1. (2012) Presc Lett 19(2): 7
  2. Ables (2007) Am Fam Physician 75:351-8 [PubMed]
  3. Cohen (2000) Gastroenterol Clin North Am 29(4):775-89 [PubMed]
  4. Fashner (2015) Am Fam Physician 91(4): 236-42 [PubMed]
  5. McConaghy (2023) Am Fam Physician 107(2): 165-72 [PubMed]
  6. Meurer (2002) Am Fam Physician 65(7):1327-36 [PubMed]

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