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Helicobacter Pylori

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

  • Epidemiology
  1. Colonizes the gastric mucosa in 50% of world population and 30-40% of U.S. population
  • 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
  • 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
  • Symptoms (Asymptomatic in 90% of cases)
  • Differential Diagnosis
  • 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 symptoms
      2. Peptic Ulcer Disease
      3. 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]
  • 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) 250 mg orally four times daily for 14 days
        1. May substitute Tindazole (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
    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 Tindazole (Tindamax) 500 mg orally twice daily for 14 days
  3. References
    1. Chey (2017) Am J Gastroenterol 112(2):212-239 +PMID:28071659 [PubMed]
  • Protocols
  • Adults Resistant Cases
  1. General for failed therapy
    1. Step Up to 4-5 agent therapy without Metronidazole
    2. Consider adding Rifabutin (Mycobutin)
      1. Qasim (2005) Aliment Pharmacol Ther 21:91-6 [PubMed]
  2. Quadruple therapy
    1. See Quadruple therapy above under adults long
  • 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]
  • Management
  • Consider maintenance antisecretory therapy
  1. Maintenance management: 50% of treatment dose
  2. Indications
    1. Complicated Peptic Ulcer Disease
    2. Elderly or frail