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
• Australia, 25–30% of the population is infected, with the prevalence increasing with age
• in some indigenous communities, prevalence is 2–3 times higher than in nonindigenous communities

Associated conditions

• Dyspepsia 
• Peptic Ulcer Disease
  • Duodenal Ulcers: 95% related to H. pylori
  • Gastric Ulcers: 70-80% related to H. pylori
• Stomach Cancer (epithelial or lymphoid)
  • 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	Quick and inexpensive Highly sensitive and specific Not suitable for monitoring post-eradication because that would entail further gastroscopy
Endoscopy & Histology & Culture	Offers additional information on degree and pattern of inflammation	ExpensiveHighly sensitive and specificCan detect early changes of MALT lymphoma
Non-invasive
Serology	Presence of H. pylori-specific IgG antibodies	low diagnostic accuracy of 80–84%. 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	High positive predictive valueHigh negative predictive value Suitable and recommended as the post-eradication monitoring testNot widely available
Stool antigen test	Presence of H. pylori antigen in the stool	sensitivity 91%  specificity 93% 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 Suitable for pre-treatment diagnosis and post-treatment monitoring Unpleasantness associated with the means of specimen collection

• H pylori eradication
  • Esomeprazole 20mg PO BD for 7 days PLUS
  • Amoxicillin 1g BD 7 days PLUS
  • Clarithromycin 500mg PO BD for 2 days

Resistance is increasing markedly

• 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 standard dose bd	clarithromycin 500 mg bd	metronidazole 500 mg bd
14 days	PPI standard dose bd	colloidal bismuth subcitrate 120 mg qid	tetracycline 500 mg qid(cannot be replaced with doxycycline because of different pharmacokinetics)	metronidazole 400 mg qid
10 days	5 days of PPI standard dose bd	amoxicillin 1000 mg bd	followed by 5 days of PPI standard dose bd/clarithromycin 500 mg bd/ tinidazole 500 mg bd
third line (‘rescue/salvage’) therapies
14 days	PPI standard dose bd	bismuth subcitrate 120 mg qid	furazolidone 200 mg bd	tetracycline 500 mg qid**#
14 days	PPI standard dose bd	moxicillin 1000 mg bd	rifabutin 150 mg bd	ciprofloxacin 500 mg bd
NEED TGA-SAS approval for: Colloidal bismuth subcitrate (De-Nol), tetracycline and furazolidone are (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 BDlansoprazole 30 mg/day BDomeraprazole 20 mg/day BDpantoprazole 40 mg/day BDrabeprazole 20 mg/day BD
Common side effectsPPIs Headache and diarrhoeaClarithromycin Gastrointestinal (GI) upset, diarrhoea, and altered tasteAmoxicillin GI upset, diarrhoea, and headacheMetronidazole Tends to be dose related, a metallic taste, dyspepsia, a disulfiram-like reaction with alcohol consumptionTetracycline GI upset, photosensitivityBismuth subcitrate Darkening of the tongue and stool, nausea, and GI upsetFurazolidone 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 anaemiaRifabutin 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

• Follow up testing
  • Post treatment urea breast test 4 weeks after treatment
  • Withhold PPI 2 weeks before
  • H2 antagonists don’t affect test
  • May need repeat scopes if ulcer/malignancy/assess healing if complicated
  • Consider PPI when using NSAIDs in the future