Peptic Ulcer Disease and H. pylori

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GI NOTES

Peptic Ulcer Disease and H. pylori

Key points

The two main causes of peptic ulcers are H. pylori and NSAIDs or aspirin.
Test for active infection with a urea breath test, stool antigen, or gastric biopsy. Stop PPIs for 2 weeks and antibiotics or bismuth for 4 weeks first.
First-line therapy (ACG 2024): bismuth quadruple therapy for 14 days. Rifabutin triple or vonoprazan-amoxicillin dual therapy are alternatives if there is no penicillin allergy.
Do not use clarithromycin triple therapy unless the strain is known to be clarithromycin-susceptible.
Confirm eradication in everyone, at least 4 weeks after finishing treatment.

1. Causes and presentation

Common: H. pylori, NSAIDs, aspirin (even low dose).
Less common: Zollinger-Ellison syndrome (gastrinoma), malignancy, CMV or HSV, ischemia, cocaine or methamphetamine, smoking, severe physiologic stress, idiopathic (H. pylori-negative, NSAID-negative).
Symptoms: epigastric pain or dyspepsia; many ulcers, especially NSAID ulcers, are silent until a complication.
Complications: bleeding (most common), perforation, penetration (for example into the pancreas), gastric outlet obstruction.

Think of Zollinger-Ellison syndrome with multiple or refractory ulcers, ulcers beyond the duodenal bulb, ulcers with diarrhea, or a family history of MEN1.

2. Who to test for H. pylori

Active or past peptic ulcer disease (unless cure was documented)
Gastric MALT lymphoma; after endoscopic resection of early gastric cancer
Uninvestigated dyspepsia without alarm features (test and treat), especially under age 60
Long-term low-dose aspirin users, and people starting long-term NSAIDs
Unexplained iron deficiency anemia, immune thrombocytopenia
First-degree relative with gastric cancer; household members of an infected person

Test	Best use	Notes
Urea breath test	Diagnosis and test of cure	Hold PPI 2 weeks, antibiotics and bismuth 4 weeks
Stool antigen (monoclonal)	Diagnosis and test of cure	Same holding rules as the breath test
Biopsy (histology, rapid urease, culture or molecular)	During endoscopy	Molecular testing or culture gives antibiotic susceptibility
Serology	Not recommended	Stays positive after cure; does not show active infection

3. Treatment

FIGURE: H. PYLORI TREATMENT PATHWAY (SUSCEPTIBILITY UNKNOWN)

Positive test for active infection

Bismuth quadruple therapy, 14 days

If no penicillin allergy: rifabutin triple, or vonoprazan + amoxicillin dual, 14 days

Test of cure at least 4 weeks later (PPI off 2 weeks)

Negative: done

Still positive: choose a regimen not used before; consider susceptibility testing

Original diagram based on the ACG 2024 H. pylori guideline.

Regimen	Components (14 days)	Notes
Bismuth quadruple (preferred)	PPI twice daily + bismuth subcitrate or subsalicylate four times daily + tetracycline 500 mg four times daily + metronidazole 500 mg three to four times daily	Works regardless of clarithromycin resistance. Warn about black stools.
Rifabutin triple	Omeprazole + amoxicillin + rifabutin (co-packaged product taken three times daily)	Alternative in penicillin-tolerant patients
Vonoprazan dual	Vonoprazan 20 mg twice daily + amoxicillin 1 g three times daily	Alternative in penicillin-tolerant patients
Clarithromycin-based triple	PPI or vonoprazan + amoxicillin + clarithromycin	Only if clarithromycin susceptibility is confirmed
Levofloxacin-based	PPI + amoxicillin + levofloxacin	Only if fluoroquinolone susceptibility is confirmed

Many patients labeled penicillin-allergic are not truly allergic. Penicillin allergy evaluation can open up amoxicillin-based regimens.

4. Managing the ulcer

PPI once daily for 4 to 8 weeks (duodenal) or 8 weeks (gastric); longer if the ulcer is large or NSAIDs must continue.
Stop NSAIDs if at all possible. If they are essential, use the lowest dose with a PPI; a COX-2 inhibitor plus PPI for the highest-risk patients.
Biopsy gastric ulcers to exclude cancer. Consider repeat EGD in 8 to 12 weeks for gastric ulcers that looked suspicious, were not biopsied, or have no clear cause.
Bleeding ulcers: see the Upper and Lower GI Bleeding note.
Perforation: free air under the diaphragm, peritonitis. Needs urgent surgical consultation.

5. High-yield pearls

H. pylori testing during an acute ulcer bleed can be falsely negative; repeat if negative.
Clarithromycin resistance is common in the US, which is why empiric clarithromycin triple therapy fell out of favor.
Each re-treatment should use antibiotics the patient has not received before, when possible.
Treating H. pylori lowers the risk of gastric cancer, especially in people with a family history.

Self-check questions

Which tests show active H. pylori infection?
What is the preferred empiric first-line regimen?
When is clarithromycin triple therapy acceptable?
How long after treatment should you test for cure?

Answers: (1) Urea breath test, stool antigen, or gastric biopsy. Serology does not. (2) Bismuth quadruple therapy for 14 days. (3) Only when the strain is known to be clarithromycin-susceptible. (4) At least 4 weeks after finishing antibiotics, with PPI stopped 2 weeks before.

References

Chey WD, Howden CW, Moss SF, et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2024;119(9):1730-1753.
Malfertheiner P, Megraud F, Rokkas T, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022;71(9):1724-1762.
Laine L, Barkun AN, Saltzman JR, Martel M, Leontiadis GI. ACG Clinical Guideline: Upper Gastrointestinal and Ulcer Bleeding. Am J Gastroenterol. 2021;116(5):899-917.
Lanza FL, Chan FK, Quigley EM. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009;104(3):728-738.

For educational purposes only. This note does not replace clinical judgment or local protocols. Check doses against current labeling and institutional guidance.