Helicobacter Pylori

See Also

Epidemiology

Helicobacter Pylori colonizes the gastric mucosa in 50% of world population and 30-40% of U.S. population
Helicobacter Pylori is the most common cause of Peptic Ulcer Disease (surpassing NSAID induced ulcers)

Pathophysiology

Helicobacter Pylori characteristics
1. Spiral-shaped (helical), facultative anaerobic, Gram Negative Rod in the Vibrionaceae family
2. Genus Helicobacter, but previously classified as Campylobacter pylori
3. Motile with multiple flagella
4. Colonizes gastric mucosa or epithelial lining
Sources
1. Acquired in early childhood via fecal-oral transmission

Associated Conditions

Dyspepsia
Peptic Ulcer Disease
1. Duodenal Ulcers: 95% related to H. pylori
2. Gastric Ulcers: 70-80% related to H. pylori
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)

See Dyspepsia
See Peptic Ulcer Disease

Differential Diagnosis

See Dyspepsia Causes
See Medication Causes of Dyspepsia

Labs

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
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
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
References

Management
General

Do not indiscriminately test and treat H. pylori
1. Test only symptomatic patients consistent with H. pylori infection
2. Test for H. pylori only if intending to treat with eradication therapy
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. Test for Antibiotic Resistance prior to use
3. Levofloxacin resistance is also growing
  1. Test for Antibiotic Resistance prior to use
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
Test for H. pylori before treatment
1. See Helicobacter pylori Noninvasive Testing
Test 4-6 weeks after treatment
1. Indications
  1. ACG Guidelines recommend testing ALL Patients for eradication after treatment
  2. Persistant Dyspepsia or other related symptoms
  3. Peptic Ulcer Disease
  4. Mucosal-Associated Lymphoid Tumor (MALT Lymphoma)
  5. Gastric Adenocarcinoma
2. Preparation
  1. Discontinue Proton Pump Inhibitors 2-4 weeks prior to testing
  2. Patients may use H2 Blockers or Aluminum and Magnesium Salt Antacids during this time
3. Testing options to confirm H. pylori eradication
Protocol pearls
1. Treatment duration: Treat for 14 days to maximize eradication rates
2. Use at least 3 agents in most cases (generally avoid 2 agent regimens, esp. for salvage therapy)
3. If failed therapy - see resistant cases below
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
Adult Preferred Initial Protocols (Treatment Naive)

Bismuth Quadruple Therapy (BQT, 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 300 to 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
PCAB Dual Therapy (Voquezna Dual Pack)
1. Take all agents for 14 days
  1. Vonoprazan 20 mg orally twice daily AND
  2. Amoxicillin 1000 mg orally twice daily
References
1. Chey (2017) Am J Gastroenterol 112(2):212-239 +PMID:28071659 [PubMed]

Protocols
Adults Resistant Cases (Preferred for Treatment Salvage)

General for failed therapy
1. Step Up to 4-5 agent therapy without Metronidazole
Quadruple therapy
1. See Quadruple therapy above
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]

Protocols
Adult Resistant Cases (Requires Antibiotic Sensitivity testing)

Precautions
1. These protocols depend on Antibiotic sensitivity testing (Clarithromycin or Levofloxacin)
PCAB Triple Therapy (Voquezna Triple Pack)
1. Confirm H. pylori sensitivity to Clarithromycin prior to use (growing resistance)
2. Take all agents for 14 days
  1. Vonoprazan 20 mg orally twice daily AND
  2. Amoxicillin 1000 mg orally twice daily AND
  3. Clarithromycin 500 mg orally twice daily
3. References
  1. Kiyotoki (2020) Intern Med 59(2):153-61 +PMID: 31243237 [PubMed]
Concomitant Quadruple Therapy (Triple Therapy with Metronidazole)
1. Background
  1. Confirm H. pylori sensitivity to Clarithromycin prior to use (growing resistance)
  2. Replaces the older triple therapy or LAC protocol (Lasoprazole-Amoxicillin-Clarithromycin)
    1. Addition of Metronidazole significantly improves efficacy
  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
Levofloxacin Based Therapy
1. Do not use if Levofloxacin-based therapy has been used in the past
2. Confirm H. pylori sensitivity to Levofloxacin prior to use (growing resistance)
3. Take all three agents for 14 days
  1. Proton Pump Inhibitor twice daily AND
  2. Amoxicillin 1000 mg orally twice daily AND
  3. Levofloxacin 500 mg orally daily

Protocols
Children

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
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)
References
1. Gold (2000) J Pediatr Gastroenterol Nutr 31:490-7 [PubMed]

Protocols
Pregnancy

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
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

Management
Consider maintenance antisecretory therapy

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

References

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