What are the doses of Bismuth Quadruple Therapy (BQT) for H. pylori infection?

Bismuth Quadruple Therapy (BQT) Dosing for H. pylori Eradication

The standard BQT regimen consists of bismuth subcitrate 120-140 mg three to four times daily, tetracycline 500 mg four times daily, metronidazole 500 mg three to four times daily, and a standard-dose PPI twice daily for 14 days, though 10 days may be acceptable in areas with low metronidazole resistance. 1, 2

Standard Dosing Components

Bismuth Salts

• Bismuth subcitrate: 120-140 mg three to four times daily 1, 2, 3
• Bismuth subsalicylate: 262 mg, 2 tablets four times daily (alternative formulation) 1
• Dosing depends on the specific bismuth formulation used 1

Tetracycline

• Tetracycline hydrochloride: 500 mg four times daily 1, 2
• Critical warning: Doxycycline should never be substituted for tetracycline due to significantly inferior eradication rates 1, 2, 4

Metronidazole

• Standard dosing: 500 mg three to four times daily 1, 2
• Alternative: 400 mg four times daily 1
• Tinidazole may be substituted for metronidazole 1

Proton Pump Inhibitor (PPI)

• Standard-dose PPI twice daily 1, 2
• Preferred PPIs: rabeprazole 20 mg or esomeprazole 20 mg twice daily 2
• Other options: pantoprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg twice daily 1
• Avoid pantoprazole when possible due to relatively lower potency 2
• Administer 30 minutes before meals on an empty stomach 1

Treatment Duration

First-Line Therapy

• 14 days is the preferred duration, particularly in areas with high or unknown metronidazole resistance 1, 2
• 10 days may be acceptable only in populations with documented low metronidazole resistance 1, 5, 6
• The Toronto Consensus recommends 14 days for all first-line treatments 1, 7
• Maastricht V/Florence agrees with 14 days unless 10 days has been proven locally effective 1, 7

Evidence Supporting Duration Choice

• Studies show 10-day and 14-day regimens achieve similar eradication rates (>95% per-protocol) in low metronidazole resistance populations 5, 6
• However, in areas with high or unknown metronidazole resistance, 14-day therapy is superior 1
• The 10-day regimen costs approximately 25% less but should only be used when local resistance patterns are favorable 5

Simplified Twice-Daily Dosing Alternative

A twice-daily regimen has been validated: pantoprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate 240 mg, all given twice daily with midday and evening meals 5

• This simplified regimen achieved 95-96% per-protocol eradication rates 5
• Improved patient compliance compared to four-times-daily dosing 5
• Earlier studies suggest twice-daily dosing of tetracycline and bismuth may be equally effective as four-times-daily 1

Critical Dosing Considerations

Metronidazole Resistance

• Metronidazole resistance significantly impacts efficacy but can be overcome by increasing dose and duration 2, 7
• In populations with high metronidazole resistance, 14-day therapy is essential 1, 3
• The addition of bismuth helps overcome metronidazole resistance through synergistic effects 1, 7

Suboptimal Regimens to Avoid

• Low-dose metronidazole (1000 mg total daily) is suboptimal, achieving only 77.3% eradication rates even with 14-day therapy 8
• This demonstrates that adequate metronidazole dosing (1500-2000 mg daily) is critical 8

Component Optimization

• The doses and dosing intervals of bismuth and tetracycline have not been fully optimized 1
• Lower doses and twice-daily administration appear equally effective but require further validation 1
• All four components (PPI, bismuth, tetracycline, metronidazole) are essential for optimal efficacy 2

Tolerability and Adverse Effects

• BQT is considered one of the less tolerable H. pylori therapies 1, 2, 3
• Common side effects include fatigue, gastrointestinal discomfort, nausea, loose stools, and taste perversion 5, 8
• Adverse effects are generally mild and rarely require treatment discontinuation 5, 6, 9
• The 10-day regimen has lower incidence of adverse effects compared to 14 days (22.6% vs 28.5%) 6
• Fatigue, discomfort, and vomiting are more common with 14-day therapy 5

Clinical Context for BQT Use

First-Line Indications

• Recommended in areas with high clarithromycin resistance (>15-20%) 2, 3, 7
• Preferred for patients with true penicillin allergy 1, 7
• Achieves >80% eradication rates even in high-resistance areas 3

Second-Line/Rescue Therapy

• Recommended after failure of clarithromycin-containing triple therapy 1, 7
• Should not reuse antibiotics that previously failed, except metronidazole when combined with bismuth 1
• After two failed therapies, susceptibility testing should guide further treatment 1, 7