01Purpose and principlesWhat the treatment does and how it fits into care.
H. pylori is usually acquired early in life and establishes long-term gastric mucosal infection. Disease expression depends on bacterial, host and environmental factors: antral-predominant inflammation favours duodenal ulcer, while corpus atrophy and intestinal metaplasia increase gastric cancer risk. Eradication heals the causal infection and substantially reduces recurrent ulcer risk, but established atrophy or metaplasia may retain a need for risk-based surveillance.
Testing must answer a defined question. In uncomplicated dyspepsia without a cancer-pathway feature, a breath or stool test can support a test-and-treat strategy. When endoscopy is independently indicated because of dysphagia, bleeding, anaemia, weight loss or another concern, do not delay it merely to complete non-invasive testing. Biopsy testing adds information but is vulnerable to sampling error, particularly when organisms are suppressed or redistributed by PPIs.
Eradication is combination therapy: potent acid suppression improves antibiotic activity, while two antibacterials reduce failure. Regimen choice is increasingly local because resistance and prior macrolide, nitroimidazole or fluoroquinolone exposure matter. Verify the allergy history, check pregnancy and interactions, explain the short but intensive schedule, and provide a written plan for missed doses and adverse effects.
Key points
- H. pylori causes chronic active gastritis and is a major driver of duodenal and gastric ulcer, gastric adenocarcinoma and gastric MALT lymphoma.
- Use a carbon-13 urea breath test or validated stool antigen test for uncomplicated non-invasive assessment because each detects current infection rather than remote antibody exposure.
- Stop a proton-pump inhibitor for two weeks before breath or stool testing and avoid antibiotics or bismuth for four weeks where clinically safe to reduce false-negative results.
- Near-patient serology performs inadequately and should not be used; laboratory serology cannot distinguish active from past infection and cannot prove eradication.
- During indicated endoscopy, histology and rapid urease testing can diagnose infection, but biopsy site, recent PPI, bleeding and patchy colonisation affect sensitivity.
- NICE first-line eradication uses a seven-day twice-daily PPI-based combination with two antibiotics, chosen around true penicillin allergy and previous clarithromycin or metronidazole exposure.
- Treatment failure should trigger adherence and exposure review, an alternative regimen and local antimicrobial advice rather than repetition of the same antibiotic pair.
- A test of cure is particularly important after ulcer disease, persistent symptoms, MALT lymphoma or later-line treatment; perform it after the appropriate medicine washout.
02Indications, selection and cautionsWho may benefit, who needs urgent treatment and important alternatives.
Intermittent epigastric discomfort, nausea or meal-related symptoms without referral features may justify non-invasive testing, but symptoms cannot distinguish H. pylori from functional dyspepsia or reflux.
Previous or current gastric or duodenal ulcer, especially without a sufficient NSAID explanation, is a strong indication to seek active infection and later document eradication.
Dysphagia, qualifying age–weight-loss combinations, suspicious mass, progressive vomiting or unexplained iron-deficiency anaemia requires appropriate expedited investigation; a stool test must not become a gatekeeper.
Coffee-ground vomiting, melaena, syncope, sudden severe pain or peritonism may represent bleeding or perforation. Stabilise and involve acute services before routine eradication planning.
Gastric MALT lymphoma has a close association with H. pylori; testing and eradication should be coordinated with the specialist lymphoma and upper-GI team because response assessment is histological.
Persistent infection after one or more courses demands the exact drug, dose, duration, adherence, adverse effects and prior non-eradication antibiotic history, not simply the phrase 'triple therapy failed'.
03Assessment before treatmentTests and checks that guide safe selection.
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
Carbon-13 urea breath testFirst step - Why
- Detect urease activity from current gastric H. pylori non-invasively.
- Interpretation and limitations
- A positive result supports active infection. A negative test is reliable only when preparation was adequate; repeat after two weeks without PPI and four weeks without antibiotics or bismuth if suppression probably caused a false negative.
- 02
Laboratory stool antigen test - Why
- Identify active infection before treatment or during appropriately timed follow-up.
- Interpretation and limitations
- Use a validated laboratory assay and the same medicine washout as breath testing. Watery stool, recent bleeding and suppressive medicines can impair performance; local laboratories specify accepted samples.
- 03
Endoscopic biopsy testing - Why
- Diagnose infection when gastroscopy is required for another clinical reason.
- Interpretation and limitations
- Rapid urease testing and histology can be combined. Sampling antrum and corpus improves detection in treated or atrophic stomachs; a negative result during bleeding or PPI therapy may need subsequent non-invasive confirmation.
- 04
Laboratory serology - Why
- Provide selected evidence of exposure when active tests are unsuitable and a validated assay exists.
- Interpretation and limitations
- Antibodies may remain positive long after cure, so serology cannot confirm active infection or treatment success. NICE advises against office-based serological kits because performance is inadequate.
- 05
Culture or molecular resistance testing - Why
- Guide later-line treatment when empirical combinations have failed.
- Interpretation and limitations
- Availability varies and usually requires endoscopic biopsy. A specialist uses susceptibility results with previous exposure and local resistance data; negative culture can reflect transport or suppression rather than absence.
- 06
Test of eradication - Why
- Confirm that treatment removed active infection in clinically important settings.
- Interpretation and limitations
- Use breath or validated stool antigen testing after antibiotics are complete and after appropriate PPI washout. NICE specifically links ulcer follow-up testing to the 6–8-week review window; do not use serology.
04Treatment approachPreparation, options, escalation and aftercare.
01PrepareCreate a valid test windowFirst stepNon-invasive H. pylori testing is appropriate and no urgent endoscopic feature supersedes it.+
- 1Check PPI, antibiotic and bismuth use, arrange a two-week PPI washout and four-week antibiotic or bismuth interval when safe, and offer temporary symptom measures that do not invalidate testing.
- 2Choose carbon-13 breath or validated laboratory stool antigen testing based on availability, patient preference and ability to provide a valid specimen; avoid office antibody kits.
- 3AlternativeIf stopping acid suppression is unsafe or endoscopy is already indicated, discuss an alternative diagnostic strategy rather than accepting a predictably low-sensitivity result.
02EradicateSelect a complete combinationAn active-infection test is positive and treatment is clinically appropriate.+
- 1Verify penicillin allergy, pregnancy, renal or liver impairment, interacting medicines, QT risk and prior exposure to clarithromycin, metronidazole and fluoroquinolones.
- 2Prescribe the current NICE and local-formulary combination as one reconciled seven-day course, clearly stating twice-daily timing and which medicine replaces which when allergy or resistance risk changes the plan.
- 3Explain adherence, metallic taste, diarrhoea, alcohol avoidance with metronidazole according to product advice, red-flag adverse effects and the later testing plan before the patient leaves.
03RescueManage persistent infectionSymptoms persist after treatment or a correctly timed active test remains positive.+
- 1Distinguish persistent infection from persistent dyspepsia: confirm test timing, review adherence and record every antimicrobial used both within and outside eradication regimens.
- 2AlternativeUse an alternative NICE-listed or locally approved regimen that avoids the failed antibiotic exposure, seeking microbiology or gastroenterology input after repeated failure or complex allergy.
- 3After later-line therapy, document eradication with a valid active test and investigate continuing symptoms on their merits rather than continuing empirical antibiotics.
05Regimens, contraindications and interactionsTreatment details and the circumstances that modify them.
First-line PPI-based H. pylori eradication combination
NICE uses seven days of a PPI twice daily plus amoxicillin 1 g twice daily and either clarithromycin or metronidazole twice daily; confirm current antibiotic strengths and selection in the local formulary.Never prescribe antibiotic monotherapy. Verify immediate and severe delayed penicillin allergy, previous macrolide or nitroimidazole exposure, pregnancy, liver and renal function, QT-prolonging combinations and major CYP3A interactions; use the penicillin-allergy or rescue pathway when indicated.
06Complications, monitoring and follow-upAdverse effects, response and longer-term review.
- Confirm that the patient obtained and completed every component, and document missed doses or early cessation because this changes interpretation of failure.
- Review clinically important rash, anaphylaxis, severe or persistent diarrhoea, neuropathic symptoms, jaundice, palpitations and interacting-drug toxicity promptly.
- Arrange a correctly timed breath or stool test where cure confirmation is indicated, recording the last PPI, antibiotic and bismuth dates.
- For gastric ulcer, coordinate repeat endoscopy and active-infection reassessment at 6–8 weeks according to lesion size, histology and the specialist plan.
- If symptoms continue despite confirmed eradication, reconsider ulcer healing, reflux, functional dyspepsia, biliary or pancreatic disease and cancer features rather than repeating antimicrobials.
07Special situationsVariants, exceptions and circumstances that change the usual approach.
The washout is diagnostic
A technically excellent breath or stool assay can still be falsely negative when bacterial activity has been suppressed by recent PPI, bismuth or antibiotics.
Antibodies outlive infection
Serological positivity may persist after successful treatment, making it unsuitable for a test of cure and potentially misleading in low-prevalence settings.
Symptoms do not prove failure
Functional dyspepsia and reflux commonly persist after microbiological cure, so further antibiotics should depend on an active-infection result rather than discomfort alone.
Exposure extends beyond eradication
A recent clarithromycin course for pneumonia or metronidazole for dental infection matters when selecting gastric therapy even though it was not labelled an H. pylori regimen.
Cancer risk may persist
Eradication removes an important carcinogenic driver but does not erase established extensive atrophy, intestinal metaplasia or inherited risk that may warrant surveillance.
08Common pitfallsFrequent interpretation and management errors.
- 01
Testing during PPI treatment and accepting a negative result without checking preparation.
- 02
Using office-based antibody testing to diagnose current infection or demonstrate cure.
- 03
Prescribing eradication from symptoms alone without an active positive test or endoscopic indication.
- 04
Ignoring antibiotics taken for other conditions when selecting clarithromycin, metronidazole or a fluoroquinolone.
- 05
Repeating the identical failed regimen without assessing adherence, allergy and resistance risk.
- 06
Letting a test-and-treat plan delay endoscopy for dysphagia, bleeding, weight loss or progressive vomiting.