H. pylori eradication agents

• Definition

• H. pylori eradication agents are drugs used in combination regimens to eliminate Helicobacter pylori, a gram-negative spiral bacterium implicated in chronic gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma

• These regimens combine antimicrobial agents, acid suppression drugs, and sometimes bismuth compounds to maximize bacterial eradication rates and minimize resistance development

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• Rationale for Combination Therapy

• H. pylori resides beneath the gastric mucus layer and within the mucosa, where acid suppression enhances antibiotic penetration and bacterial susceptibility

• Monotherapy is ineffective and fosters resistance; thus, at least two antibiotics plus an acid-suppressing agent are recommended

• Optimal regimens achieve >80–90% eradication in compliant patients

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• Core Drug Classes and Examples

1. Antimicrobial Agents

   • Macrolides: Clarithromycin – inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit

   • Nitroimidazoles: Metronidazole, tinidazole – cause DNA strand breakage via free radical generation under anaerobic conditions

   • Tetracyclines: Tetracycline – inhibits protein synthesis by binding to the 30S ribosomal subunit

   • Aminopenicillins: Amoxicillin – inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins

   • Fluoroquinolones: Levofloxacin, moxifloxacin – inhibit bacterial DNA gyrase and topoisomerase IV (used in salvage regimens)

2. Acid Suppression Agents

   • Proton Pump Inhibitors (PPIs): Omeprazole, esomeprazole, lansoprazole, pantoprazole – irreversibly inhibit the gastric H⁺/K⁺-ATPase pump, raising gastric pH to improve antibiotic stability and activity

   • Potassium-Competitive Acid Blockers (P-CABs): Vonoprazan – rapidly and reversibly inhibit the proton pump with more potent and sustained acid suppression than PPIs

3. Bismuth Compounds

   • Bismuth subsalicylate / bismuth subcitrate – antimicrobial activity against H. pylori, prevent bacterial adhesion, and protect gastric mucosa

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• Standard Regimens

1. Clarithromycin-Based Triple Therapy (10–14 days)

   • PPI (standard or double dose) twice daily

   • Clarithromycin 500 mg twice daily

   • Amoxicillin 1 g twice daily (or metronidazole 500 mg twice daily if penicillin allergic)

   • Preferred in regions with low (<15%) clarithromycin resistance

2. Bismuth Quadruple Therapy (10–14 days)

   • PPI twice daily

   • Bismuth subsalicylate 525 mg four times daily (or bismuth subcitrate 120–300 mg four times daily)

   • Tetracycline 500 mg four times daily

   • Metronidazole 500 mg three or four times daily

   • Effective in areas with high clarithromycin resistance or after triple therapy failure

3. Concomitant Therapy (10–14 days)

   • PPI twice daily

   • Clarithromycin 500 mg twice daily

   • Amoxicillin 1 g twice daily

   • Metronidazole or tinidazole 500 mg twice daily

   • All agents started simultaneously; effective against resistant strains

4. Levofloxacin-Based Therapy (10–14 days)

   • PPI twice daily

   • Levofloxacin 500 mg once daily

   • Amoxicillin 1 g twice daily

   • Used as a salvage regimen after first-line failure

5. Rifabutin-Based Triple Therapy (10–14 days)

   • PPI twice daily

   • Amoxicillin 1 g twice daily

   • Rifabutin 150 mg twice daily

   • Reserved for multiple treatment failures due to risk of myelotoxicity

6. Vonoprazan-Containing Regimens (7–14 days)

   • Vonoprazan 20 mg twice daily

   • Clarithromycin 500 mg twice daily

   • Amoxicillin 750–1000 mg twice daily

   • Offers high eradication rates even with shorter duration

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• Contraindications

• Known allergy to any antibiotic in the regimen (e.g., penicillin allergy with amoxicillin)

• Significant drug interactions with clarithromycin (potent CYP3A4 inhibitor)

• Bismuth subsalicylate avoided in salicylate allergy or in children/teens with viral illness (Reye’s syndrome risk)

• Pregnancy considerations – tetracycline and fluoroquinolones contraindicated

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• Adverse Effects

1. Antibiotics

   • Clarithromycin: nausea, diarrhea, altered taste, QT prolongation

   • Amoxicillin: diarrhea, rash, rare anaphylaxis

   • Metronidazole/tinidazole: metallic taste, GI upset, disulfiram-like reaction with alcohol

   • Tetracycline: photosensitivity, GI upset, tooth discoloration (children)

   • Levofloxacin: tendon rupture risk, QT prolongation, CNS effects

2. Bismuth compounds

   • Black stools, dark tongue, constipation

3. PPIs/P-CABs

   • Headache, diarrhea, hypomagnesemia (long-term), possible increased risk of C. difficile infection

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• Precautions

• Adjust antibiotic doses in renal or hepatic impairment where indicated

• Assess local antibiotic resistance patterns before regimen selection

• Emphasize adherence – incomplete courses reduce eradication rates and promote resistance

• Avoid alcohol during and for 72 hours after nitroimidazole use

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• Drug Interactions

• Clarithromycin: increases levels of statins, warfarin, theophylline, carbamazepine, digoxin via CYP3A4 inhibition

• PPIs: may reduce absorption of certain drugs (e.g., ketoconazole, atazanavir); omeprazole may reduce clopidogrel activation

• Bismuth subsalicylate: additive bleeding risk with anticoagulants, antiplatelets, NSAIDs

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• Clinical Considerations

• First-line regimen choice depends on antibiotic resistance, patient allergy status, prior macrolide exposure, and regional guidelines

• Confirmation of eradication recommended 4+ weeks after completion of therapy using urea breath test, stool antigen test, or gastric biopsy

• Reinfection rates are generally low in adults but higher in certain populations

• Salvage therapy should avoid previously used antibiotics to reduce resistance risk