Helicobacter pylori: test-and-treat, eradication regimens, and confirming cure

Helicobacter pylori — ubiquitous, curable, and linked to ulcers and stomach cancer

Helicobacter pylori is a Gram-negative spiral bacterium that colonises the gastric mucus layer and, without intervention, persists for life. It is acquired predominantly in childhood via intra-familial transmission and is more common in populations from high-prevalence countries including East Asia, Eastern Europe, Latin America, Africa, and the Middle East.

Approximately 25% of Australian adults are seropositive for H. pylori, though prevalence is declining in younger Australian-born people. The clinical burden is substantial: the bacterium is the primary cause of most non-NSAID peptic ulcers, a major driver of gastric MALT lymphoma (where eradication leads to regression in ~75% of early-stage cases), and a WHO Class 1 carcinogen for gastric adenocarcinoma with an estimated ~1% lifetime gastric cancer risk in infected individuals.

Most people with H. pylori have no symptoms. The GP’s role is identifying appropriate indications for testing, selecting an effective eradication regimen in the context of rising antibiotic resistance, supporting adherence, and confirming successful eradication.

A. Core clinical — the AU general-practice framework

Who to test

eTG Antibiotic — H. pylori and GESA guidelines recommend testing in:

• Dyspepsia in patients under 55 without alarm features — test-and-treat strategy; endoscopy if positive and non-responsive to eradication, or if refractory
• Confirmed current or past peptic ulcer disease — testing and eradication mandatory
• Gastric MALT lymphoma — eradication is primary treatment for localised disease
• Iron deficiency anaemia after exclusion of other causes — H. pylori impairs iron absorption and can precipitate deficiency
• Immune thrombocytopenia (ITP) — eradication improves platelet count in a proportion of patients
• First-degree family history of gastric cancer — targeted testing in high-risk individuals
• Long-term NSAID or antiplatelet use with ulcer history — eradication before continuing therapy

Alarm features that mandate endoscopy before test-and-treat: age ≥55, GI bleeding (melaena, haematemesis), iron deficiency anaemia as the presenting symptom, significant unintentional weight loss, dysphagia or odynophagia, recurrent vomiting, palpable abdominal mass, or family history of gastric cancer.

Diagnostic tests — the critical pre-test requirement

Urea breath test (UBT) — the preferred non-invasive test; the patient ingests labelled urea and exhaled CO₂ confirms active bacterial urease activity. Highly sensitive and specific. Key requirement: PPI must be stopped at least 2 weeks before the test, and antibiotics must have been completed at least 4 weeks before testing — failure to observe this washout is the leading cause of false-negative results.

Stool antigen test — equivalent sensitivity and specificity to UBT; same washout requirement applies. An alternative when UBT is unavailable.

Serology (IgG antibody) — detects prior exposure but does not distinguish active from cleared infection. Serology remains positive for months to years after successful eradication and should not be used to diagnose active infection or confirm cure.

Endoscopic biopsy — rapid urease test (CLO), histology, and culture/sensitivity are performed during gastroscopy. Culture is the gold standard for antibiotic susceptibility testing and is essential for refractory cases. PCR-based molecular susceptibility testing is emerging, particularly for detecting clarithromycin and fluoroquinolone resistance.

Adjunct investigations

Per eTG:

• FBC, iron studies — assess for associated iron deficiency anaemia
• Coeliac serology (anti-tTG IgA + total IgA) — important differential in unexplained dyspepsia or iron deficiency
• H. pylori-positive gastric biopsy findings — any histological evidence of intestinal metaplasia or atrophy warrants gastroenterology surveillance planning

B. Eradication regimens — navigating rising antibiotic resistance

The resistance context

Australian clarithromycin resistance rates are approximately 10–30% in surveillance studies, and metronidazole resistance approximately 30–50%. Tetracycline and amoxicillin resistance remain low. This resistance landscape has shifted first-line recommendations toward bismuth-based regimens, as endorsed by the ACG 2024 H. pylori Treatment Guideline.

All regimens should be 14 days — shorter courses are inferior in the modern resistance era.

First-line regimens (14 days)

1. Bismuth quadruple therapy (BQT) — increasingly preferred first-line:

• PPI twice daily (e.g., esomeprazole 20–40 mg BD)
• Bismuth subcitrate 120 mg four times daily (De-Nol)
• Metronidazole 400 mg three times daily
• Tetracycline 500 mg four times daily

BQT is recommended as first-line when clarithromycin resistance is unknown, likely, or if the patient has had prior macrolide exposure. The eClinicalMedicine 2024 non-inferiority trial showed 10-day BQT was non-inferior to 14-day in Chinese populations; Australian practice favours 14 days for higher certainty.

2. Clarithromycin triple therapy — only where local resistance is less than 15% and no prior macrolide exposure:

• PPI twice daily + amoxicillin 1 g twice daily + clarithromycin 500 mg twice daily × 14 days
• Penicillin allergy: replace amoxicillin with metronidazole 400 mg twice daily
• Klacid HP7 — the Australian PBS-listed combination pack (PPI + amoxicillin + clarithromycin) is Authority Required (Streamlined); convenient where clarithromycin resistance is presumed low

3. Concomitant non-bismuth quadruple therapy:

• PPI + amoxicillin + clarithromycin + metronidazole all twice daily × 14 days — when bismuth is unavailable and clarithromycin triple is unsuitable

Second-line / rescue regimens

4. Levofloxacin-based triple therapy:

• PPI twice daily + amoxicillin 1 g twice daily + levofloxacin 500 mg daily × 14 days
• Reserve due to fluoroquinolone stewardship concerns: tendinopathy, Achilles rupture, and a signal for aortic dissection. Fluoroquinolone resistance is also rising. PBS Authority Required.

5. Bismuth quadruple (if not used first-line).

6. Susceptibility-guided therapy — refer to gastroenterology for culture-based regimen selection after two eradication failures.

7. Rifabutin-based triple — specialist-led salvage option; rifabutin has TB treatment obligations that complicate its use.

Drug interactions and counselling essentials

AMH highlights important interactions:

• Clarithromycin is a potent CYP3A4 inhibitor — significant interactions with statins (myopathy risk), calcium channel blockers, anticoagulants, immunosuppressants, and some antidepressants; review the drug list before prescribing
• Metronidazole — disulfiram-like reaction with alcohol; patients must abstain during and for 48 hours post-treatment
• Tetracycline — photosensitivity; take on an empty stomach; not during pregnancy (second or third trimester); avoid in children under 8
• Fluoroquinolone (levofloxacin) — separate by 2 hours from antacids, iron, or calcium; QTc-prolonging combination risk

Adherence counselling is critical — partial or interrupted courses breed resistance. Probiotic supplementation (Saccharomyces boulardii or lactobacillus 250 mg twice daily throughout the course) reduces GI side effects without compromising eradication rates.

C. Confirming eradication

Eradication confirmation 4–8 weeks post-treatment is non-negotiable per eTG. Use UBT or stool antigen — not serology. The antibody remains positive for months to years after successful eradication and will give a false reading.

Pre-test requirements again: PPI stopped ≥2 weeks, all antibiotics completed ≥4 weeks before the test.

If the post-treatment test is positive: escalate to second-line regimen with different agents. If a second regimen also fails, refer to gastroenterology for susceptibility-guided therapy.

Ongoing endoscopic surveillance is arranged by gastroenterology where: histology showed intestinal metaplasia or gastric atrophy, MALT lymphoma was diagnosed (post-eradication surveillance to confirm regression), or there is a strong family history of gastric cancer.

D. Australian operations

MBS items for H. pylori in general practice:

Standard GP consultations (items 23, 36, 44). Urea breath test (item 12533) is rebatable for initial diagnosis and post-eradication confirmation. Stool antigen (items in the 69384 range) is an alternative. Gastroscopy with biopsy (items in the 30473 range) for endoscopic diagnosis, alarm feature investigation, or MALT surveillance is specialist-initiated.

FBC (item 65070) and iron studies (item 66600) are rebatable for associated anaemia workup. The GP Chronic Condition Management Plan (GPCCMP — items 965/967) applies when H. pylori-associated chronic dyspepsia or peptic ulcer disease coexists with a chronic comorbidity.

PBS medications:

• Klacid HP7 (amoxicillin + clarithromycin + PPI) — Authority Required (Streamlined) for H. pylori eradication; the most convenient pack for clarithromycin-appropriate settings
• Bismuth subcitrate (De-Nol) — general schedule
• Tetracycline — general schedule
• Metronidazole — general schedule
• PPIs — general schedule
• Levofloxacin — Authority Required
• Rifabutin — Authority Required (TB indications; specialist H. pylori salvage use only)

Antimicrobial stewardship: document the choice of regimen, rationale for first versus second line, and any prior antibiotic exposures. This is particularly important when prescribing fluoroquinolones.

Telehealth: appropriate for post-eradication result review and pre/post-test counselling once the 12-month existing-relationship rule is met.

E. Special populations

Pregnancy. Eradication is generally deferred until after pregnancy unless there is active complicated peptic ulcer disease. Tetracycline is contraindicated in pregnancy (dental and skeletal effects in the fetus). Metronidazole should be avoided in the first trimester where possible (relative contraindication). Amoxicillin-based regimens are generally considered safer. Discuss timing with the patient and specialist if eradication is urgent.

Older adults. CYP3A4 inhibition from clarithromycin is more significant in older patients on polypharmacy — particularly those on statins, anticoagulants, or immunosuppressants. BQT avoids clarithromycin and is often preferable. Tetracycline carries a higher diarrhoea risk in older patients.

Patients from high-prevalence regions. Migrants from East Asia, Eastern Europe, Latin America, Africa, and the Middle East have higher H. pylori prevalence and, in some populations, higher rates of virulent CagA-positive strains. A family history of gastric cancer in these contexts warrants a lower threshold for testing and consideration of post-eradication surveillance.

MALT lymphoma. Low-grade gastric MALT lymphoma confined to the mucosa or submucosa regresses in approximately 75% of cases after H. pylori eradication alone. Management is led jointly by gastroenterology and haematology-oncology, with GP role in monitoring for relapse.

When to escalate

Refer to the emergency department for: acute GI bleeding (haematemesis or melaena) or suspected peptic ulcer perforation or gastric outlet obstruction — these are surgical emergencies.

Same-week gastroenterology referral for: alarm features (as above) requiring urgent gastroscopy, suspected gastric cancer or MALT lymphoma, first presentation with complicated PUD, or pregnancy with active complicated ulcer disease.

Routine gastroenterology referral for: two failed eradication courses, refractory dyspepsia post-eradication, complex drug interactions, or suspected Zollinger-Ellison syndrome.

What this article is and is not

This is general health information drawn from eTG, AMH, GESA, RACGP, and ACG 2024 guidelines. It is not personal medical advice and does not create a doctor–patient relationship. Treatment decisions — including antibiotic selection and surveillance planning — are made with your own GP and gastroenterologist.

AU consumer resources: HealthDirect — Helicobacter pylori, Better Health Channel — Stomach ulcers.

For GI bleeding (black or blood-stained vomit or stools): present to an emergency department or call 000.

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Sources cited

1. Therapeutic Guidelines (eTG) — Antibiotic: Helicobacter pylori
2. GESA — Helicobacter pylori resources
3. Australian Medicines Handbook
4. RACGP — H. pylori in general practice
5. PBS — Klacid HP7 and eradication listings
6. ACG 2024 H. pylori Treatment Guideline
7. eClinicalMedicine 2024 — BQT duration study
8. HealthDirect — Helicobacter pylori
9. Better Health Channel — Stomach ulcers
10. Cochrane — H. pylori eradication for non-ulcer dyspepsia