Helicobacter pylori infection

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Helicobacter pylori colonises gastric mucus for decades unless eradicated. Infection is often asymptomatic but drives chronic active gastritis and substantially contributes to duodenal and gastric ulceration.

A test-and-treat strategy is appropriate for selected dyspepsia without alarm features. Endoscopy is used when referral criteria, bleeding, ulcer complication, persistent symptoms or another structural diagnosis changes management.

Successful eradication depends on taking every dose, acid suppression and choosing antibiotics around prior exposure and local resistance. Repeating the same failed combination without review promotes further resistance.

Safe care for helicobacter pylori infection depends on separating physiological instability from diagnostic uncertainty: resuscitation and infection-control actions proceed while targeted samples, imaging and source-control decisions are arranged.

Antimicrobial decisions in helicobacter pylori infection should document indication, likely source, allergy phenotype, pregnancy possibility, renal and hepatic function, previous microbiology and the planned review or stop point.

Key points

Helicobacter pylori is a chronic gastric infection associated with peptic ulcer disease, gastric adenocarcinoma and gastric MALT lymphoma.
Use urea breath testing or stool antigen testing for active infection; serology cannot reliably distinguish current from past infection.
Withhold proton-pump inhibitors for two weeks and antibiotics and bismuth for four weeks before active-infection testing when clinically safe.
Alarm features or suspected bleeding, perforation or cancer take priority over a routine test-and-treat dyspepsia pathway.
NICE supports seven-day twice-daily proton-pump inhibitor triple therapy chosen around penicillin allergy, previous macrolide or metronidazole exposure and local resistance.
Typical non-allergic regimens use amoxicillin 1 g twice daily plus clarithromycin 500 mg twice daily or metronidazole 400 mg twice daily.
Penicillin allergy requires a non-amoxicillin regimen selected carefully, with specialist advice when previous clarithromycin and metronidazole exposure limits options.
Confirm eradication with an active test when indicated, using the same medicine washouts and an adequate interval after treatment.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Chronic gastric colonisation

Helicobacter pylori is usually acquired through close-contact oral or faecal-oral transmission and can persist for life without effective eradication.

Host and environmental risk

Crowded childhood living conditions, household exposure and origin from higher-prevalence settings increase infection probability, while host genetics influence inflammatory injury.

Coexisting mucosal injury

NSAIDs, aspirin, smoking and severe physiological stress can compound ulcer risk even when Helicobacter pylori is an important causal factor.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Urease-supported survival
Bacterial urease generates ammonia within gastric mucus, buffering local acid and enabling motile organisms to survive near epithelial cells.
2
Chronic active gastritis
Adhesion, virulence factors and persistent immune activation damage gastric epithelium and alter somatostatin, gastrin and acid physiology.
3
Ulcer formation
Antral-predominant infection can increase acid delivery to the duodenum, while pangastritis weakens gastric mucosal defence and promotes ulceration.
4
Neoplastic progression
Long-standing inflammation can drive atrophy, intestinal metaplasia, dysplasia and adenocarcinoma, while antigenic stimulation can produce gastric MALT lymphoma.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Uncomplicated dyspepsia

Epigastric pain or burning, postprandial fullness, early satiety, nausea and reflux-like symptoms may occur, but no symptom pattern proves Helicobacter pylori.

Peptic ulcer pattern

Localised epigastric pain, nocturnal symptoms or previous ulcer raises probability, while NSAID and aspirin exposure can coexist and magnify complication risk.

Bleeding presentationRed flag

Melaena, haematemesis, iron-deficiency anaemia, postural symptoms or collapse may reflect an infected ulcer and requires an emergency bleeding pathway.

Cancer alarm featuresRed flag

Progressive dysphagia, weight loss, persistent vomiting, anaemia, upper abdominal mass or appropriate age-risk criteria require urgent endoscopic assessment.

Treatment failure context

Incomplete adherence, previous macrolide or nitroimidazole use, continued acid suppression before testing and premature retesting commonly explain an apparent persistent infection.

Context changes probability

Recent healthcare exposure, antimicrobial use, travel, procedures, devices, pregnancy, immune compromise and previous resistant isolates materially change the likely diagnosis and treatment risk in helicobacter pylori infection.

Red flags requiring action

Haematemesis, melaena, syncope or haemodynamic instability requires emergency upper gastrointestinal bleeding care.
Sudden severe pain with guarding or rigidity suggests peptic ulcer perforation and requires urgent surgical assessment.
Progressive dysphagia, persistent vomiting, weight loss, anaemia or an epigastric mass requires urgent cancer-pathway assessment.
New dyspepsia in an older adult or a high-risk context should be managed using current age and alarm referral criteria.
Persistent symptoms after eradication require adherence, resistance, alternative diagnosis and malignancy risk review.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Urea breath testFirst step
Why
Detect active infection non-invasively before treatment or after eradication.
Interpretation and limitations
A positive result supports current infection when medicine washouts are adequate. PPIs, antibiotics and bismuth can cause false-negative results.
02
Monoclonal stool antigen test
Why
Provide an alternative active-infection test suitable for initial diagnosis and confirmation of eradication.
Interpretation and limitations
Use a validated local assay and the same PPI, antibiotic and bismuth washouts. Gastrointestinal bleeding can complicate interpretation.
03
Upper gastrointestinal endoscopy with biopsy
Why
Investigate alarm features, ulcer complications or persistent symptoms and obtain tissue for histology or organism testing.
Interpretation and limitations
Biopsy location, PPI use and recent antibiotics affect sensitivity; endoscopy also evaluates malignancy and alternative mucosal disease.
04
Full blood count, ferritin and urea
Why
Assess occult or overt bleeding and iron deficiency when clinical features indicate.
Interpretation and limitations
Iron deficiency or a disproportionate urea rise in bleeding changes urgency but neither finding identifies Helicobacter pylori by itself.
05
Previous antibiotic and allergy record
Why
Choose an eradication combination with the best chance of success and lowest avoidable risk.
Interpretation and limitations
Document the penicillin reaction precisely and identify prior clarithromycin or metronidazole courses because exposure predicts resistance and regimen failure.
06
Host and prescribing assessment
Why
Identify modifiers that alter diagnostic yield, severity and safe prescribing for helicobacter pylori infection.
Interpretation and limitations
Before eradication, document the penicillin reaction, pregnancy possibility, prior macrolide and metronidazole exposure, QT risk, hepatic function and interacting medicines that change regimen safety.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Functional dyspepsia

Chronic upper abdominal symptoms without structural disease commonly persist despite eradication and require a symptom-based management approach.

Gastro-oesophageal reflux

Retrosternal burning and regurgitation may overlap with dyspepsia but reflect reflux physiology rather than proving gastric infection.

Gastric or oesophageal cancer

Weight loss, dysphagia, anaemia, persistent vomiting or mass requires urgent endoscopy because infection does not exclude malignancy.

Biliary or pancreatic disease

Postprandial right upper-quadrant pain, jaundice, back radiation or abnormal liver and pancreatic enzymes should redirect anatomical investigation.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01TESTUse an active infection assayFirst stepDyspepsia is suitable for non-invasive Helicobacter pylori test-and-treat management without alarm features.

1Check age and alarm referral criteria, ulcer history, NSAID or aspirin exposure, family history and whether symptoms need endoscopy rather than non-invasive testing.
2Stop proton-pump inhibitors for two weeks and antibiotics and bismuth for four weeks before urea breath or stool antigen testing when safe.
3Treat a confirmed active infection with a guideline-concordant seven-day regimen selected around allergy, previous antimicrobial exposure and local resistance.
4Give adherence and adverse-effect advice and explain which indication, symptom course or risk factor requires confirmation of eradication or endoscopy.

02REFERPrioritise structural assessmentBleeding, dysphagia, weight loss, persistent vomiting, anaemia, mass, severe pain or another alarm feature is present.

1Use the emergency bleeding or perforation pathway immediately when physiology, haematemesis, melaena or peritonism indicates an acute complication.
2Refer for urgent endoscopy according to current suspected-cancer criteria rather than delaying assessment for a community test-and-treat course.
3At endoscopy biopsy suspicious lesions and obtain appropriate gastric samples while accounting for recent PPI and antibiotic exposure.
4AlternativeTreat confirmed Helicobacter pylori, but continue investigation of malignancy, ulcer complication or alternative disease independently of eradication.

03FAILUREManage persistent infection rationallyA properly timed active test remains positive after a completed eradication course or symptoms persist unexpectedly.

1Verify exactly which medicines and doses were taken, missed doses, vomiting, adverse effects and whether PPI or antibiotics distorted the retest.
2Review all previous macrolide, metronidazole and quinolone exposure and the penicillin-allergy phenotype before selecting a different combination.
3Seek gastroenterology or microbiology advice after repeated failure, complicated ulcer disease or restricted antibiotic options; consider culture or molecular susceptibility where available.
4Do not equate persistent dyspepsia automatically with persistent infection; assess functional dyspepsia, reflux, biliary disease, medication injury and malignancy risk.

04REASSESSReview response and diagnosisSymptoms persist, physiology worsens or expected improvement in helicobacter pylori infection has not occurred.

1Repeat observations and examination, reconsider the anatomical source and look actively for obstruction, collection, perforation, ischaemia or another diagnosis complicating helicobacter pylori infection.
2Review eradication adherence, vomiting, washout timing, previous antibiotic exposure and interaction risk; select a different evidence-based combination or specialist susceptibility testing rather than recycling failure.
3EscalationEscalate to the relevant medical, surgical, microbiology, infection or public-health team when source control, resistant infection, outbreak management or specialist follow-up is required for helicobacter pylori infection.
4Give dyspepsia safety-net advice covering haematemesis, melaena, syncope, progressive dysphagia, weight loss, persistent vomiting and the route for urgent endoscopic assessment.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Eradicates Helicobacter pylori in a non-allergic adult when prior macrolide exposure and local resistance do not make clarithromycin unsuitable.

PPI, amoxicillin and clarithromycin

Give a standard-dose proton-pump inhibitor twice daily, amoxicillin 1 g twice daily and clarithromycin 500 mg twice daily for seven days.

Check immediate penicillin allergy, macrolide exposure, QT risk, liver disease and interactions including statins, warfarin and colchicine; modify choices using current BNF and local guidance.

Provides a NICE-supported clarithromycin-sparing triple regimen for selected adults without penicillin allergy.

PPI, amoxicillin and metronidazole

Give a standard-dose proton-pump inhibitor twice daily, amoxicillin 1 g twice daily and metronidazole 400 mg twice daily for seven days.

Check penicillin reaction, previous metronidazole exposure, warfarin interaction, hepatic impairment and neurological toxicity; explain avoidance of alcohol during treatment and for the product-specified interval afterwards.

Avoids amoxicillin while providing a NICE-supported eradication option when both antibiotics remain appropriate.

PPI, clarithromycin and metronidazole

For penicillin allergy, give a standard-dose proton-pump inhibitor twice daily, clarithromycin 500 mg twice daily and metronidazole 400 mg twice daily for seven days.

Confirm true penicillin allergy and review prior clarithromycin and metronidazole use, QT prolongation, interactions, liver disease, pregnancy possibility and the high failure risk when resistance is likely.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Peptic ulcer disease

Persistent inflammation and altered acid defence produce gastric or duodenal ulceration with pain, occult blood loss or recurrent symptoms.

Upper gastrointestinal bleeding

Ulcer erosion into a vessel causes melaena, haematemesis, anaemia or shock and requires emergency resuscitation and endoscopic haemostasis.

Perforation or obstruction

Deep ulceration can perforate into the peritoneum or scar the gastric outlet, causing peritonitis, severe pain or persistent vomiting.

Gastric neoplasia

Chronic atrophic gastritis increases gastric adenocarcinoma risk, and sustained antigen stimulation is causally associated with gastric MALT lymphoma.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

During therapy ask about missed doses, vomiting, severe diarrhoea, rash, palpitations, neuropathic symptoms and clinically important medicine interactions.
Do not assess eradication from symptom relief alone because dyspepsia may persist after cure or improve despite ongoing infection.
When confirmation is indicated, use urea breath or stool antigen testing at least four weeks after antibiotics and after a two-week PPI washout.
Investigate persistent anaemia, bleeding, weight loss or dysphagia even if eradication testing becomes negative.
After repeated failure document every previous combination and obtain specialist advice rather than recycling antibiotics empirically.
At every review of helicobacter pylori infection, confirm that the working diagnosis still fits the trajectory and that microbiology or imaging has not revealed a source requiring a different intervention.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Serology cannot prove cure

Antibodies may remain positive long after eradication, so serology is unsuitable for confirming whether viable infection persists.

Washout protects sensitivity

PPIs suppress bacterial load and antibiotics or bismuth may partially treat infection, producing a false-negative breath, stool or biopsy test.

Symptoms and infection diverge

Functional dyspepsia can persist after successful eradication, while important ulcer disease can be clinically quiet until bleeding occurs.

Previous exposure predicts failure

Recent macrolide or metronidazole use increases resistance probability and should directly influence the selected eradication combination.

Cancer risk is reduced not erased

Eradication lowers future gastric cancer risk but does not eliminate established atrophy, metaplasia or an existing malignant lesion.

Document the decision boundary

For helicobacter pylori infection, record why treatment, observation, admission, isolation or source control was chosen and which finding would trigger a change of plan.

11Common pitfallsFrequent interpretation and management errors.

01
Do not use Helicobacter pylori serology as a routine test of eradication after treatment.
02
Do not perform a urea breath or stool antigen test during PPI therapy and accept a negative result without considering washout.
03
Do not let a positive infection test delay urgent endoscopy for bleeding, progressive dysphagia, weight loss or another alarm feature.
04
Do not repeat clarithromycin or metronidazole blindly after treatment failure without reviewing previous exposure and adherence.
05
Do not describe every proton-pump inhibitor dose as identical; use the standard-dose twice-daily product regimen specified in current guidance.
06
Do not allow a positive colonisation-prone test, device sample or nonspecific inflammatory marker to outweigh the clinical syndrome when assessing helicobacter pylori infection.