H pylori management
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The best sources are Harrison's (THERAPY OF H. PYLORI), Yamada's (Therapy and management), and Washington Manual. Let me read these in parallel.
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Helicobacter pylori Management
Indications for Testing and Treatment
H. pylori is a class I carcinogen and should be eradicated in any patient who tests positive, regardless of symptom status. Key indications include:
- Peptic ulcer disease (active or past history)
- Functional dyspepsia
- MALT lymphoma
- After resection of early gastric cancer
- First-degree relatives of gastric cancer patients
- Unexplained iron deficiency anemia or ITP
Diagnosis
| Test | Notes |
|---|---|
| Urea breath test (UBT) | Most accurate non-invasive test; sensitivity/specificity ~95%. Best for confirming eradication. Stop PPIs ≥2 weeks before testing. |
| Stool antigen test (HpSA) | Sensitivity/specificity 91–96%. FDA-approved for initial diagnosis and post-treatment confirmation. PPIs do not affect accuracy. |
| Serum antibody | Detects past or current infection; stays positive up to 18 months after eradication — cannot confirm successful treatment. |
| Rapid urease assay (CLO test) | Endoscopic biopsy-based; may be falsely negative on PPI therapy. |
| Histopathology | Gold standard at endoscopy; also detects dysplasia/cancer. |
Serology is not used to confirm eradication.
Eradication Regimens
First-Line Options
1. Bismuth-based quadruple therapy (preferred first-line, especially where clarithromycin resistance >15%)
- PPI (standard dose bid) + bismuth subsalicylate 525 mg qid + metronidazole 250–500 mg qid + tetracycline 500 mg qid × 14 days
2. Concomitant (non-bismuth quadruple) therapy (first-line alternative when bismuth unavailable)
- PPI + clarithromycin 500 mg bid + amoxicillin 1 g bid + metronidazole 500 mg bid × 14 days
3. Clarithromycin-based triple therapy (acceptable first-line if local clarithromycin resistance <15%)
- PPI + clarithromycin 500 mg bid + amoxicillin 1 g bid × 14 days
4. Sequential therapy
- PPI + amoxicillin 1 g bid × 5–7 days, then PPI + clarithromycin 500 mg bid + metronidazole 500 mg bid × 5–7 days
5. Hybrid therapy
- PPI + amoxicillin 1 g bid × 7 days, then PPI + amoxicillin 1 g bid + clarithromycin 500 mg bid + metronidazole 500 mg bid × 7 days
6. Levofloxacin triple therapy (first-line option)
- PPI + levofloxacin 250 mg bid + amoxicillin 1 g bid × 10–14 days
For penicillin allergy:
- PPI + clarithromycin 500 mg bid + metronidazole 500 mg bid × 14 days
Salvage/Second-Line Therapy
After initial failure, avoid repeating antibiotics already used (especially clarithromycin and metronidazole — resistance is the most common cause of failure).
| Regimen | Notes |
|---|---|
| Bismuth quadruple (if not used first-line) | Good option after clarithromycin-based failure |
| Levofloxacin triple or fluoroquinolone sequential | After bismuth quadruple failure |
| Rifabutin-based triple: rifabutin 150–300 mg daily + amoxicillin 1 g bid + PPI × 10 days | FDA-approved salvage; available as Talicia® |
| High-dose dual amoxicillin/PPI therapy | Alternative salvage |
| Culture-guided therapy | If ≥2 prior regimens have failed |
Vonoprazan (Novel Acid Suppression)
Vonoprazan is a potassium-competitive acid pump antagonist (P-CAP) approved by the FDA. It may be superior to PPIs when combined with antibiotics for H. pylori eradication and holds Fast Track FDA status for combinations with amoxicillin ± clarithromycin.
Post-Treatment Confirmation
- Test for eradication at least 4 weeks after completing therapy (and 2 weeks off PPIs).
- Preferred tests: urea breath test or stool antigen test.
- Serology should not be used.
- Eradication rates in clinical practice are frequently <90% due to antibiotic resistance and patient factors — confirmation is therefore mandatory.
Key Principles
- Treat for 14 days — longer duration improves eradication rates vs. 7 days.
- Antibiotic resistance (particularly clarithromycin and metronidazole) is the primary driver of treatment failure.
- Local/regional resistance patterns should guide first-line regimen selection where data are available.
- Pre-packaged kits (Prevpac®, Helidac®) exist but are generally not recommended as optimal therapy due to shorter duration and suboptimal dosing.
— Yamada's Textbook of Gastroenterology, 7e | Harrison's Principles of Internal Medicine, 22e | Washington Manual of Medical Therapeutics
H pylori management
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Helicobacter pylori Management
Why Treat
H. pylori is a class I carcinogen. Eradication reduces:
- Peptic ulcer recurrence from 50–90% → <5% at 12–24 months
- Risk of gastric cancer by ~35% (meta-analysis of RCTs)
- Risk of metachronous gastric cancer after endoscopic resection of early gastric cancer
Treat all patients who test positive, regardless of symptom status.
Indications for Testing
- Peptic ulcer disease (active or historical)
- Functional/uninvestigated dyspepsia (test-and-treat strategy in patients ≤45 y without alarm features)
- MALT lymphoma
- After resection of early gastric cancer
- First-degree relatives of gastric cancer patients
- Unexplained iron deficiency anemia, ITP
- Long-term NSAID/aspirin use (prior to initiation)
Diagnosis
| Test | Notes |
|---|---|
| ¹³C Urea breath test (UBT) | Most accurate non-invasive test; sensitivity/specificity ~95%. Stop PPIs ≥2 weeks before testing. |
| Stool antigen test (HpSA) | Sensitivity/specificity 91–96%. FDA-approved for initial diagnosis and confirming eradication. PPI use does not affect accuracy. |
| Serum antibody (IgG) | Cannot confirm eradication — remains positive up to 18 months post-treatment. Useful only for initial screening in low-prevalence settings. |
| Rapid urease test (CLO test) | Endoscopic biopsy-based; falsely negative on PPI therapy. |
| Histopathology | Gold standard at endoscopy; mandatory for gastric ulcers to exclude malignancy. |
Eradication Regimens
First-Line Therapy
Selection hinges on local clarithromycin resistance rates (threshold: 15%).
Where clarithromycin resistance is low (<15%)
Clarithromycin-based triple therapy × 14 days
- PPI (double dose preferred, e.g., omeprazole 40 mg bid) + clarithromycin 500 mg bid + amoxicillin 1 g bid
- Eradication ~75–90%; 14 days outperforms 7 days by ~5%
Where clarithromycin resistance is high (>15%) — or resistance unknown
1. Bismuth-based quadruple therapy × 14 days (preferred first-line globally)
PPI bid + bismuth subsalicylate 525 mg qid + metronidazole 250–500 mg qid + tetracycline 500 mg qid Eradication ~85–90%
2. Concomitant (non-bismuth quadruple) therapy × 14 days (when bismuth unavailable)
PPI bid + clarithromycin 500 mg bid + amoxicillin 1 g bid + metronidazole 500 mg bid
3. Sequential therapy × 10–14 days
PPI + amoxicillin 1 g bid × 5–7 days → then PPI + clarithromycin 500 mg bid + metronidazole 500 mg bid × 5–7 days
4. Hybrid therapy × 14 days
PPI + amoxicillin 1 g bid × 7 days → then PPI + amoxicillin + clarithromycin + metronidazole × 7 days
5. Levofloxacin triple therapy × 10–14 days
PPI + levofloxacin 250 mg bid + amoxicillin 1 g bid
Penicillin allergy:
PPI + clarithromycin 500 mg bid + metronidazole 500 mg bid × 14 days
Second-Line Therapy (after first failure)
Key principle: never repeat an antibiotic already used, especially clarithromycin or metronidazole (resistance is the leading cause of failure).
| Regimen | Notes |
|---|---|
| Bismuth quadruple (if not used first-line) | After clarithromycin triple failure |
| Levofloxacin triple or fluoroquinolone-sequential | After bismuth quadruple failure |
| Quinolone-based bismuth quadruple × ≥10 days | Excellent second-line option (Goldman-Cecil) |
Salvage Therapy (≥2 prior failures)
| Regimen | Notes |
|---|---|
| Rifabutin + omeprazole + amoxicillin × 10 days (Talicia®) | FDA-approved; preferred salvage |
| High-dose dual therapy: high-dose PPI + amoxicillin 1 g bid × 14 days | Alternative salvage |
| Culture/sensitivity-guided therapy | Mandatory after ≥2 failures |
Role of Vonoprazan
Vonoprazan is a potassium-competitive acid pump antagonist (P-CAP) — a novel class superior to PPIs in maintaining intragastric pH. FDA-approved for H. pylori in combination with amoxicillin ± clarithromycin. May outperform standard PPI-based regimens, especially in clarithromycin-resistant strains.
Confirming Eradication
- Mandatory after every treatment course (eradication rates in clinical practice are frequently <90%)
- Test ≥4 weeks after completing antibiotics (and ≥2 weeks off PPIs/bismuth)
- Preferred tests: UBT or stool antigen
- After successful eradication, recurrence risk is <1% per year
- Continue PPI only if symptoms persist or complicated ulcer disease is present
Adjuncts
- Probiotics added to triple therapy appear to hasten symptom resolution and modestly increase eradication rates
- Double-dose PPI (omeprazole 40 mg bid equivalent) improves eradication by ~6–10%
- Continue acid suppression after antibiotics only if symptoms persist or gastric ulcer requires healing confirmation
— Goldman-Cecil Medicine, 26e | Yamada's Textbook of Gastroenterology, 7e | Sleisenger & Fordtran's Gastrointestinal and Liver Disease
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