Peptic Ulcer Disease & H. pylori

📋 Key Information Summary

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Peptic ulcer disease (PUD) encompasses gastric and duodenal ulcers, primarily caused by H. pylori infection or NSAID use.
Non-serological tests for H. pylori (urea breath test, faecal antigen, biopsy-based) require PPIs withheld for ≥2 weeks and antibiotics for ≥4 weeks prior.
Serology is not used for test of cure due to inability to distinguish active from past infection.
First-line eradication: Bismuth quadruple therapy (PPI + bismuth subsalicylate/subcitrate + tetracycline + metronidazole) for 14 days is a key empiric option in Australia.
PPI-clarithromycin triple therapy (PPI + amoxicillin + clarithromycin) is first-line only where clarithromycin resistance is confirmed <15%.
Second-line or rescue therapies include levofloxacin-based or rifabutin-based regimens after treatment failure.
Test of cure (urea breath test or faecal antigen) is mandatory at least 4 weeks after completing eradication therapy.
Acute upper GI bleeding from ulcers: Endoscopic therapy with dual modality (e.g., clipping + injection) is standard, followed by IV PPI infusion.
Forrest classification (Ia, Ib, IIa, IIb, IIc, III) guides endoscopic intervention and re-bleeding risk.
All gastric ulcers require endoscopic biopsy to exclude malignancy, even if benign in appearance.
NSAID-related ulcer risk stratification guides gastroprotection: age >65, prior PUD, anticoagulant/steroid use, high-dose NSAID are major risk factors.
High-risk patients on NSAIDs require a PPI co-prescription or a COX-2 selective inhibitor with PPI.
Test-and-treat for H. pylori is recommended before starting long-term NSAID therapy.

H. pylori Diagnosis

Accurate diagnosis of Helicobacter pylori infection is fundamental to PUD management. Choice of test depends on clinical context, prior therapy, and local availability.

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Critical Pre-Test Preparation: For all non-serological tests, proton pump inhibitors (PPIs) must be withheld for at least 2 weeks, and antibiotics and bismuth compounds for at least 4 weeks prior to testing to avoid false negatives.

Non-Invasive Tests

GP Orderable Urea Breath Test (UBT) Gold standard non-invasive test. Uses ¹³C-labelled urea. High sensitivity and specificity (>95%). Available in most Australian pathology centres (MBS item 69496). Suitable for diagnosis and test of cure.

GP Orderable Faecal Antigen Test (FAT) Monoclonal antibody-based stool test. Comparable accuracy to UBT. Useful where UBT is unavailable. MBS item 69487.

GP Orderable Serology (IgG) Detects antibodies but cannot distinguish active from past infection. Not suitable for test of cure. May be the only option in patients with recent PPI/antibiotic use or bleeding, but false positives are common in low-prevalence populations.

Invasive (Biopsy-Based) Tests – Require Endoscopy

Specialist / Endoscopy Rapid Urease Test (e.g., CLOtest) Biopsy placed in urea medium; colour change indicates presence of H. pylori urease. Quick (1-24 hrs) but sensitivity drops with low bacterial load, PPI use, or bleeding.

Specialist / Endoscopy Histology Biopsies from antrum and corpus assessed by pathologist. Allows assessment of gastritis, atrophy, intestinal metaplasia, and malignancy.

Specialist / Endoscopy Culture & Sensitivity Gold standard for confirming eradication failure and guiding tailored therapy. Essential where antimicrobial resistance is suspected. Not routinely performed in primary care.

A "test-and-treat" strategy (using UBT or FAT) is appropriate for young patients (<50 years) with uncomplicated dyspepsia and no alarm features. Endoscopy is indicated for patients >50 years, with alarm features (dysphagia, weight loss, vomiting, anaemia), or treatment failure.

Eradication Therapy

Successful eradication cures H. pylori-related ulcers and prevents recurrence. Regimen choice is based on local resistance patterns, prior exposure, and allergies. All courses are 14 days unless specified.

First-Line Therapy

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Bismuth Quadruple Therapy

PPI + Bismuth + Tetracycline + Metronidazole

Adult RegimenStandard dose PPI (e.g., esomeprazole 20 mg) BD + bismuth subsalicylate 300 mg (2 tabs) QID + tetracycline 500 mg QID + metronidazole 400 mg TDS. Duration: 14 days.

Key NotesEmpiric first-line where clarithromycin resistance is ≥15% or unknown. Effective against metronidazole-resistant strains when combined with bismuth.

PBS Status✔ PBS General Benefit (for individual components)

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PPI-Amoxicillin-Clarithromycin (PAC)

Standard Triple Therapy

Adult RegimenStandard dose PPI BD + amoxicillin 1 g BD + clarithromycin 500 mg BD. Duration: 14 days.

Key NotesFirst-line only where local clarithromycin resistance is confirmed <15%. Avoid if prior macrolide exposure.

PBS Status✔ PBS General Benefit (for individual components)

Second-Line / Rescue Therapies (After First-Line Failure)

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Levofloxacin-Based Triple

PPI + Amoxicillin + Levofloxacin

Adult RegimenStandard dose PPI BD + amoxicillin 1 g BD + levofloxacin 500 mg daily. Duration: 14 days.

Key NotesHigh efficacy. Use if fluoroquinolone resistance is low. Caution in areas with high TB prevalence (rifabutin may be preferred).

PBS Status✔ PBS Restricted Benefit (levofloxacin for H. pylori eradication)

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Rifabutin-Based Triple

PPI + Amoxicillin + Rifabutin

Adult RegimenStandard dose PPI BD + amoxicillin 1 g BD + rifabutin 150 mg BD. Duration: 14 days.

Key NotesReserved for multiple failures. Monitor for myelosuppression (neutropenia). Not for use in areas with high TB incidence without specialist oversight.

PBS StatusAuthority Required (rifabutin for H. pylori eradication)

High-Dose Dual Therapy

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High-Dose Dual PPI-Amoxicillin

Optimised Acid Suppression

Adult RegimenHigh-dose PPI (e.g., esomeprazole 40 mg TDS or equivalent) + amoxicillin 1 g TDS. Duration: 14 days.

Key NotesEmerging strategy relying on potent acid suppression to allow amoxicillin efficacy. May be used in penicillin allergy to other regimens (with caution) or as salvage.

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Mandatory Test of Cure: Confirm eradication with a non-invasive test (UBT or FAT) at least 4 weeks after completion of therapy. Do not use serology. Confirm eradication in all patients with ulcer complications, MALT lymphoma, or after rescue therapy.

PUD Complications

Complications of peptic ulcer disease include bleeding, perforation, gastric outlet obstruction, and, for gastric ulcers, potential malignancy. Management requires urgent intervention.

Bleeding Ulcer

Acute upper GI bleeding is a medical emergency. Risk stratification and endoscopic therapy are cornerstone.

Forrest Class	Appearance	Re-bleed Risk	Management
Ia	Spurting haemorrhage	Very High (~90%)	Immediate endoscopic therapy + IV PPI infusion
Ib	Oozing haemorrhage	High (~50-60%)	Endoscopic therapy + IV PPI infusion
IIa	Non-bleeding visible vessel	High (~40-50%)	Endoscopic therapy + IV PPI infusion
IIb	Adherent clot	Moderate (~20-30%)	Consider clot removal → treat underlying lesion (IIa). IV PPI.
IIc	Flat pigmented spot	Low (~5-10%)	No endoscopic therapy. Oral PPI.
III	Clean base ulcer	Very Low (~2-5%)	No endoscopic therapy. Oral PPI.

Endoscopic & Pharmacological Therapy

Dual modality endoscopic therapy (e.g., injection of adrenaline + mechanical therapy with haemoclips or thermal coagulation) is superior to monotherapy for high-risk stigmata. Newer options include Over-The-Scope Clips (OTSC) and haemospray for refractory bleeding.

IV PPI Therapy: Following endoscopic haemostasis, high-dose IV PPI infusion (e.g., esomeprazole 80 mg bolus then 8 mg/hr for 72 hrs) is standard. Intermittent IV PPI (e.g., 40 mg BD) may be non-inferior in lower-risk patients (Forrest IIb).

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High-Risk Patient: Haemodynamic instability, Forrest Ia/Ib/IIa ulcer, or significant comorbidity requires ICU/HDU admission, endoscopic therapy, and continuous PPI infusion.

Perforation

Sudden onset severe abdominal pain. Presents with peritonitis and free air on imaging. Requires urgent surgical consultation for laparoscopic or open repair, often with an omental patch. Concurrent H. pylori testing and eradication post-operatively is essential.

Gastric Outlet Obstruction

Caused by chronic inflammation and scarring from duodenal or pyloric channel ulcers. Presents with vomiting, early satiety, and weight loss. Initial management is gastric decompression with NG tube, IV PPI, and fluid/electrolyte correction. Endoscopic balloon dilation may be attempted; surgery is reserved for refractory cases.

Malignancy Exclusion in Gastric Ulcers

All gastric ulcers identified at endoscopy must be biopsied (multiple samples from ulcer edge and base) to exclude adenocarcinoma. Even with benign histology, repeat endoscopy with biopsy in 6-8 weeks is mandatory to confirm complete healing and non-malignant aetiology.

NSAID-related Ulcers

NSAIDs (including aspirin) are a major cause of PUD. Management focuses on risk assessment, gastroprotection, and H. pylori eradication.

Risk Stratification

Low Risk

No Risk Factors

Young patient, short-term NSAID use, no other risk factors.

Action: NSAID alone may be considered. Use lowest effective dose.

Moderate Risk

1-2 Risk Factors

Age >65, prior PUD history, concurrent corticosteroid or anticoagulant (e.g., warfarin, DOAC), high-dose/multiple NSAIDs, significant comorbidity (CVD, CKD).

Action: PPI co-prescription is mandatory. Consider COX-2 inhibitor + PPI if multiple factors.

High Risk

Complicated PUD History or Multiple Factors

Prior ulcer bleeding/perforation, especially recent. Combination of age >65 + anticoagulant + corticosteroid.

Action: Avoid NSAIDs if possible. If essential: COX-2 inhibitor + PPI. Consider alternative analgesia.

Gastroprotection Strategies

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Proton Pump Inhibitor (PPI)

Esomeprazole, Pantoprazole, etc.

RoleFirst-line gastroprotection. Superior to H2-receptor antagonists for NSAID ulcer prevention.

PBS Status✔ PBS General Benefit

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COX-2 Selective Inhibitor

Celecoxib, Etoricoxib

RoleLower GI risk than non-selective NSAIDs. Must still be combined with PPI in high-risk patients. Note increased CV risk.

PBS Status✔ PBS Restricted Benefit (for patients with GI intolerance to non-selective NSAIDs)

Low-Dose Aspirin & Gastroprotection

Low-dose aspirin (75-100 mg) for cardiovascular prophylaxis also increases ulcer risk. Patients with a history of PUD or on concurrent anticoagulants/corticosteroids require routine PPI co-prescription.

H. pylori Test-and-Treat

H. pylori infection synergistically increases NSAID ulcer risk. Test-and-treat for H. pylori is recommended before initiating long-term NSAID therapy, especially in patients with prior PUD history. Eradication reduces but does not eliminate risk; gastroprotection with PPI remains necessary in moderate-to-high-risk patients.

Special Populations

🤰 Pregnancy

Diagnosis: Serology or stool antigen preferred. UBT is likely safe but less studied.

Treatment: Delay eradication until postpartum if possible. If urgent (e.g., bleeding ulcer), bismuth is contraindicated. PPI (omeprazole preferred) + amoxicillin + metronidazole (avoid in 1st trimester) may be considered.

Gastroprotection: PPIs (omeprazole) are Category B3. Use only if clearly needed.

👶 Paediatrics

Diagnosis: UBT or stool antigen. Serology unreliable in young children.

Eradication: Weight-based dosing. PPI-amoxicillin-clarithromycin (or metronidazole if allergic) for 14 days. Bismuth quadruple not first-line in children.

🩺 Renal Impairment

Adjustments: Avoid bismuth in severe CKD. Dose-adjust metronidazole and clarithromycin for eGFR <30 mL/min. Tetracycline generally avoided (but used in bismuth quadruple with caution). PPIs safe.

🫁 Hepatic Impairment

Adjustments: Use standard PPI doses; monitor for encephalopathy. Metronidazole: reduce dose/frequency in severe cirrhosis. Clarithromycin: caution in severe impairment.

🛡️ Immunocompromised

Considerations: Higher risk of atypical infections and poor healing. Ensure complete H. pylori eradication with test of cure. Be vigilant for CMV ulcers in transplant patients.

📚 References

1. Australian Commission on Safety and Quality in Health Care (ACSQHC). National Safety and Quality Health Service Standards. 2nd ed. Sydney: ACSQHC; 2021.
2. Malfertheiner P, et al. Helicobacter pylori infection. Nat Rev Dis Primers. 2023;9(1):19.
3. Fallone CA, et al. The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults. Gastroenterology. 2016;151(1):51-69.e14.
4. Laine L, et al. Management of Patients with Ulcer Bleeding. Am J Gastroenterol. 2012;107(3):345-360.
5. The Royal Australian College of General Practitioners (RACGP). Management of dyspepsia and heartburn in general practice. East Melbourne: RACGP; 2020.
6. Medicines Australia. Australian Medicines Handbook. Adelaide: AMH; 2024.
7. Australian Government Department of Health. Pharmaceutical Benefits Scheme (PBS). Available at: pbs.gov.au.
8. National Health and Medical Research Council (NHMRC). Australian guidelines to reduce health risks from drinking alcohol. Canberra: NHMRC; 2020. [Relevance: alcohol as PUD risk factor].
9. Lanas A, Chan FKL. Peptic ulcer disease. Lancet. 2017;390(10094):613-624.
10. Australian Institute of Health and Welfare (AIHW). Aboriginal and Torres Strait Islander health performance framework. Canberra: AIHW; 2023.
11. RHDAustralia (The Australian Government Department of Health). Recognising and managing acute rheumatic fever and rheumatic heart disease. [Relevance: penicillin prophylaxis and PUD].
12. Chey WD, et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017;112(2):212-239.