H.pylori

• Spiral-shaped (helical) Gram Negative Bacteria
• Colonizes gastric mucosa or epithelial lining
• Acquired in early childhood via fecal-oral transmission
• Helicobacter pylori is strongly linked to peptic ulcer disease and is classified as a group 1 carcinogen 
• socioeconomic level seems to be the major determinant of risk of infection
• Prevalence: ~30% in Australian adults; higher among:
  • Migrants (esp. from East Asia, Mediterranean)
  • Institutionalised persons
  • Lower socioeconomic groups
  • People with a family history of PUD or gastric cancer
• Transmission: Fecal–oral or oral–oral; usually acquired in childhood

Associated conditions

• Active chronic gastritis (universal in infected)
• Dyspepsia 
• Peptic Ulcer Disease (15–20% lifetime risk)
  • Duodenal Ulcers: 95% related to H. pylori
  • Gastric Ulcers: 70-80% related to H. pylori
• Stomach Cancer (epithelial or lymphoid) (~2% lifetime risk)
  • Mucosa-associated Lymphoid Tissue (MALT)
  • Gastric adenocarcinoma

Clinical

• Reflux symptoms
• Dyspepsia – Chronic or recurrent Epigastric Pain, burning, early satiety or post-prandial fullness
• Epigastric discomfort
• Pain
• Bloating

Indications for Diagnosis and treat

• Proven indications for the diagnosis and treatment
  • Peptic ulcer disease (active or confirmed history)
  • Dyspepsia
  • Low grade gastric MALT lymphoma
  • After endoscopic resection of early gastric cancer
  • First degree relatives of patients with gastric cancer
• Conditions where evidence is inconclusive for diagnosis and treatment
  • Investigated nonulcer dyspepsia (ie. ’functional dyspepsia’: dyspepsia patients who have no ulcer at endoscopy)
  • With NSAID use
  • Gastro-oesophageal reflux disease (GORD)
    • There is no clear evidence that eradication of H. pylori infection causes gastro-oesophageal reflux disease (GORD) or exacerbates GORD
    • Helicobacter pylori eradication therapy should not be withheld due to concerns of creating or worsening GORD. 
    • Routine testing for H. pylori is not recommended in GORD. 
    • However, in patients receiving long term maintenance treatment with PPIs, H. pylori testing should be considered. 
    • Profound acid suppression affects the pattern and distribution of gastritis favouring corpus dominant gastritis and may lead to atrophic gastritis.
    • Helicobacter pylori eradication halts the progression of atrophic gastritis and may reverse the process of atrophy therefore decreasing cancer risk
  • Populations at higher risk for gastric cancer (Japan and parts of China)
    • definite evidence on whether H. pylori eradication can reduce the risk of developing gastric adenocarcinoma is lacking. 
    • It is likely that cancer risk persists for several years after the bacterium is gone
  • Unexplained iron deficiency anaemia in adults
  • Idiopathic thrombocytopenic purpura
• NSAID and H. pylori eradication
  • H. pylori eradication is of value in chronic NSAID users but is insufficient to prevent NSAID related ulcer disease completely
  • In naive NSAID users H. pylori eradication may prevent peptic ulcer and bleeding
  • For patients with a history of an ulcer complication who require subsequent therapy with an NSAID or aspirin, PPI maintenance treatment is better than H. pylori eradication in preventing ulcer recurrence and/or bleeding. Co-therapy may be an option
  • Patients taking long term aspirin and who bleed should be tested for H. pylori, and be treated for the infection if positive

Test	Mechanism	Notes
Invasive
Rapid urease test	Biopsy specimen is combined with urea and pH is measured H. pylori  converts urea to ammonia (NH3) + CO2 Test is positive for H. pylori if pH of the medium becomes more alkaline, indicated by colour change	Highly sensitive and specificn ( >90% ) quick diagnosis Not suitable for monitoring post-eradication because that would entail further gastroscopy
Endoscopy & Histology & Culture	Offers additional information on degree and pattern of inflammation	Expensive Histology: Sensitivity and specificity >95%; confirms – gastritis – malignancy – early changes of MALT lymphoma
Non-invasive
Serology	Presence of H. pylori-specific IgG antibodies	Sensitivity: ~85%; Specificity: ~79% (if no previous infection) Use: Past exposure only; not useful for test-of-cure Inexpensive and widely available. Positive predictive value (NPV) 50% — Positive in low titre indicates past exposure to H. pylori and not necessarily active colonisation — Positive in high titre reflects active colonisation — Serology can also remain positive for months to years after successful eradication negative predictive value (NPV) 98% – negative result = almost rules out current infection Not suitable for monitoring post-eradication because successful treatment does not alter IgG levels immediately
Urea breath test	Uses principle of urea metabolism by H. pylori Patient ingests radio-labelled (13c) urea followed by a measurement of the concentration of isotope-labelled CO2 exhaled Positive for H. pylori if isotope-labelled CO2 present	Sensitivity/Specificity: >95% Use: First-line for diagnosis and test-of-cure High positive predictive value High negative predictive value Use: First-line for diagnosis and test-of-cure
Stool antigen test	Presence of H. pylori antigen in the stool	Sensitivity: 91–96%; Specificity: 93–97% Use: Alternative first-line and test-of-cure option Limitations: ↓ sensitivity during GI bleeding specimens are sensitive to room temperature and must be immediately frozen after collection may be useful in children who are unable to perform a UBT

✅ Standard Triple Therapy

• Esomeprazole 20 mg orally, twice daily
• Amoxicillin 1 g orally, twice daily
• Clarithromycin 500 mg orally, twice daily
• Duration: 7 to 14 days (14 days preferred for higher eradication rates)

🔹 FIRST-LINE IN PENICILLIN-ALLERGIC PATIENTS

• PPI (standard dose) orally, twice daily
  • Esomeprazole 20 mg or
  • Lansoprazole 30 mg or
  • Omeprazole 20 mg or
  • Pantoprazole 40 mg or
  • Rabeprazole 20 mg
• Metronidazole 400 mg orally, twice daily
• Clarithromycin 500 mg orally, twice daily
• Duration: 7–14 days (preferably 14 for higher efficacy)

Note: Eradication rates ~80%, lower if metronidazole resistance present

Resistance is increasing markedly

🟡 Avoid repeating if failed once (due to clarithromycin resistance risk)

• Metronidazole resistance is very common
• Clarithromycin resistance is growing (8-12%)

First and second line therapies
7 days	PPI standard dose bd	clarithromycin 500 mg bd	amoxicillin 1000 mg bd
7 days	PPI (any) PO BD	clarithromycin 500 mg bd	metronidazole 500 mg bd
14 days	PPI (any) PO BD	Colloidal bismuth subcitrate 120 mg four times daily (empty stomach) (Bismuth-based quadruple therapy)	Tetracycline 500 mg four times daily **# (empty stomach) (cannot be replaced with doxycycline because of different pharmacokinetics)	Metronidazole 400 mg three times daily with food * All agents available via SAS in Australia
10 days	PPI (any) PO BD	amoxicillin 1000 mg bd	Levofloxacin 250 mg PO BD or 500 mg PO daily (SAS only) OR Moxifloxacin 400 mg PO daily (Quinolone-based triple therapy (10 days))
third line (‘rescue/salvage’) therapies (Any subsequent eradication regimen used after failure of the initial treatment)
10 days	PPI (any) PO BD	Amoxicillin 1 g PO BD	Rifabutin 150 mg PO BD (off-label use) (Rifabutin-based triple therapy)	Eradication: ~65–80%
NEED TGA-SAS approval for: – Colloidal bismuth subcitrate (De-Nol), – Tetracycline (SAS-category B). To prescribe or obtain these drugs for treating H. pylori infection, follow these three steps: • obtain the SAS form from the TGA website (www.tga.gov.au/docs/pdf/unapproved/sascata.pdf) • fax the completed form to the TGA for approval (it will befaxed back to you by the TGA after 1 week) • deliver the SAS form to the drug supplier to be filled
Standard PPI doses: – esomeprazole 40 mg/day BD – lansoprazole 30 mg/day BD – omeraprazole 20 mg/day BD – pantoprazole 40 mg/day BD – rabeprazole 20 mg/day BD
Common side effects PPIs  – Headache and diarrhoea Clarithromycin  – Gastrointestinal (GI) upset, diarrhoea, and altered taste Amoxicillin  – GI upset, diarrhoea, and headache – Metronidazole Tends to be dose related, a metallic taste, dyspepsia, a disulfiram-like reaction with alcohol consumption Tetracycline  – GI upset, photosensitivity Bismuth subcitrate  – Darkening of the tongue and stool, nausea, and GI upset Furazolidone  – Nausea, vomiting, headache, and malaise in up to a third of patients. – Less frequently hypersensitivity, hypotension, a disulfiram-like reaction with alcohol consumption, and mild reversible haemolytic anaemia Rifabutin  – Red discoloration of urine while using the drug. Rash, diarrhoea, nausea, vomiting, dyspepsia. -Small but serious risk of myelotoxicity and ocular toxicity. – Can select for resistance among mycobacteria

POST-ERADICATION ASSESSMENT

• Test-of-cure is mandatory in:
  • Complicated ulcers (bleeding, perforation)
  • Before stopping long-term PPI
  • Medico-legal assurance
• Preferred test: urea breath test
  • Stop PPIs ≥1–2 weeks
  • H₂ blockers can continue
  • Stop antibiotics ≥4 weeks
• Avoid: Serology (remains positive long-term)
• May need repeat scopes if ulcer/malignancy/assess healing if complicated
• Consider PPI when using NSAIDs in the future

MAINTENANCE THERAPY (If needed)

Use if:

• H. pylori eradication unsuccessful
• Ongoing NSAID requirement
• High-risk of recurrence

PPI options (once daily):

• Esomeprazole 20 mg
• Lansoprazole 30 mg
• Omeprazole 20 mg
• Pantoprazole 40 mg
• Rabeprazole 20 mg

PAEDIATRIC H. PYLORI MANAGEMENT

Prevalence: <5% in Australia

Testing NOT recommended for:

• Functional abdominal pain
• Without alarm symptoms

If testing needed:

• Stool antigen (preferred)
• Urea breath test: false positives common in children

Refer to paediatric gastroenterology

Avoid empirical treatment