Version July 2025
| Antimicrobial susceptibility testing result* | Regimen options | |
| Absence of true penicillin allergy | True penicillin allergy | |
| Clarithromycin susceptible | Clarithromycin triple (with amoxicillin) | Clarithromycin triple (with metronidazole) |
| Clarithromycin resistant | Metronidazole triple ± bismuth¶ | Optimized bismuth quadruple |
| Clarithromycin resistant, levofloxacin susceptible | Preferred options | |
| Rifabutin triple Vonoprazan dualΔ High-dose PPI dual Optimized bismuth quadruple | Optimized bismuth quadruple | |
| Nonpreferred option | ||
| Levofloxacin triple◊ | ||
| Clarithromycin resistant, levofloxacin resistant | Rifabutin triple Vonoprazan dualΔ High-dose PPI dual Optimized bismuth quadruple | Optimized bismuth quadruple |
| No testing | Select regimen based on prior Helicobacter pylori treatment regimens. Do not use clarithromycin- and levofloxacin-based regimens in the absence of confirmed H. pylori susceptibility. | |
| Salvage regimen | Drugs (doses) | Dosing frequency |
| Optimized bismuth quadruple (component therapy) | PPI standard dose§ | Twice daily |
| Bismuth subsalicylate 524 mg¥ | 4 times daily | |
| Tetracycline 500 mg‡ | 4 times daily | |
| Metronidazole 500 mg | 3 or 4 times daily | |
| Bismuth quadruple (as Pylera combination capsules plus PPI) | PPI standard dose§ | Twice daily |
| Fixed-dose combination capsules; 3 capsules deliver: bismuth subcitrate 420 mg, metronidazole 375 mg, and tetracycline 375 mg | 4 times daily | |
| Rifabutin-amoxicillin-PPI triple† | Combination pill | |
| Talicia – 4 fixed-dose combination capsules that contain omeprazole 40 mg, rifabutin 50 mg, and amoxicillin 1 g | 3 times daily | |
| Component therapy | ||
| PPI (high dose)** | 2 or 3 times daily | |
| Rifabutin 150 mg | Once or twice daily (preferred) | |
| Amoxicillin 1 g | 3 times daily | |
| Vonoprazan-amoxicillin dual (Voquezna Dual Pak) | Vonoprazan 20 mgΔ | Twice daily |
| Amoxicillin 1 g¶¶ | 3 times daily | |
| High-dose PPI dual | PPI (high dose)** | Twice or 3 times |
| Amoxicillin 1 g¶¶ | 3 times daily | |
| Clarithromycin triple | Vonoprazan 20 mg or PPI (high dose)** | Twice daily |
| Clarithromycin 500 mg | Twice daily | |
| Amoxicillin 1 g¶¶ or Metronidazole 500 mg | 3 times daily | |
| Metronidazole triple | PPI (high dose)** | Twice daily |
| Metronidazole 500 mg | 3 times daily | |
| Amoxicillin 1 g¶¶ | 3 times daily | |
| ± bismuth subsalicylate 524 mg¶¥ | 4 times daily | |
| Levofloxacin triple◊ | PPI (high dose)** | Twice daily |
| Amoxicillin 1 g¶¶ | 3 times daily | |
| Levofloxacin 500 mg | Once daily | |
BQT: bismuth quadruple therapy; CYP2C19: cytochrome P450 2C19; PPI: proton pump inhibitor.
* Antimicrobial susceptibility testing results for all options assume susceptibility to amoxicillin, tetracycline, and rifabutin. Resistance is rare for these agents.
¶ Some experts add bismuth to regimens that contain metronidazole because this may optimize its efficacy against H. pylori.
Δ High-dose PPI can be substituted for vonoprazan and vice versa.
◊ Levofloxacin-containing regimens are not preferred, due to high rates of H. pylori resistance to fluoroquinolones and potentially serious fluoroquinolone-related adverse effects. Refer to Lexidrug monographs within UpToDate for details.
§ PPIs should be taken 30 to 60 minutes prior to meals. Standard doses of oral PPIs for treatment of H. pylori infection include lansoprazole 30 mg twice daily, omeprazole 20 mg twice daily, rabeprazole 20 mg twice daily, or esomeprazole 20 mg twice daily. Pantoprazole 40 mg twice daily is a nonpreferred option due to its weaker acid inhibitory effect.
¥ In the United States, bismuth subsalicylate is available as a 262 mg chewable tablet. Bismuth subsalicylate should not be used in patients with salicylate allergy; bismuth subcitrate is an acceptable alternative.
‡ Doxycycline should not be substituted for tetracycline because doxycycline is associated with lower H. pylori eradication success.
† Low-dose rifabutin (50 mg) is only available commercially as a component of Talicia. Generic rifabutin is available only as a 150 mg capsule in the United States.
** PPIs should be taken 30 to 60 minutes prior to meals on an empty stomach. The medical literature gives varying doses and frequencies of high-dose PPI therapy in the setting of H. pylori treatment regimens as some antibiotics are more prone to the effect of gastric acid (eg, amoxicillin and clarithromycin). We typically use the following twice-daily, high-dose PPI options: lansoprazole 60 mg twice daily, omeprazole 40 mg twice daily, rabeprazole 40 mg twice daily, or esomeprazole 40 mg twice daily. 3-times-daily, high-dose PPI options (eg, omeprazole 40 mg 3 times daily or esomeprazole 40 mg 3 times daily) can be used in amoxicillin-containing salvage therapy regimens (eg, rifabutin triple therapy and high-dose PPI dual therapy). Rabeprazole or esomeprazole are preferred because they are less affected by CYP2C19 metabolism. Pantoprazole is not preferred, due to its weak gastric acid suppression.
¶¶ Alternative dosing for amoxicillin is 750 mg 3 times daily.
