01Core principlesThe concepts and mechanisms needed to understand the subject.
H pylori survives in the gastric mucus layer through urease activity and alters acid distribution. Antral-predominant infection can increase gastrin and duodenal acid exposure, while corpus-predominant inflammation promotes atrophy and lower acid secretion. The consequences include duodenal or gastric ulceration, gastric adenocarcinoma risk and mucosa-associated lymphoid tissue lymphoma, but infection may remain asymptomatic for years.
Test choice must match the question. Carbon-13 breath testing and validated laboratory monoclonal stool-antigen assays detect current infection and can document cure; the 2023 Polish Society diagnostic consensus supports both. NICE CG184 still names carbon-13 breath testing for cure and explicitly dates its insufficient stool-test evidence to 2004. This diagnostic update does not import a foreign antibiotic course into UK prescribing. Serology records immune exposure and may stay positive after eradication. Histology assesses gastritis, atrophy and neoplasia; culture or molecular resistance testing helps after repeated failure. For an interpretable breath or stool result, stop PPIs for two weeks and leave at least four weeks after antibiotics or bismuth.
Eradication succeeds only when all agents, dose, interval and duration are explicit and the patient completes them. Review penicillin allergy, previous macrolide or metronidazole exposure, QT-prolonging medicines, statins and renal or hepatic function before selecting a regimen. Persistent infection after treatment reflects resistance, adherence, reinfection or premature retesting; each possibility leads to a different correction.
Key points
- For active infection or cure, use carbon-13 breath testing or a validated laboratory monoclonal stool-antigen assay. The latter cure indication has modern 2023 consensus support; NICE CG184 retains older breath-test-only cure wording.
- Before breath or stool testing, leave two weeks without a PPI and at least four weeks after antibiotics or bismuth; antibody serology cannot establish eradication.
- Biopsy-based histology, rapid urease testing or culture is useful when endoscopy is already indicated, but sampling site and concurrent acid suppression affect yield.
- A complete licensed example is omeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg, all orally twice daily for seven days, selected only after allergy, interaction and prior-antibiotic review.
- Clarithromycin exposure and local resistance matter; do not repeat the same failed antibiotics blindly, and seek culture or specialist advice after two unsuccessful courses.
- For peptic ulcer with H pylori, NICE recommends retesting six to eight weeks after treatment begins; repeat gastric endoscopy also checks healing and excludes missed malignancy.
02Mechanisms and patternsImportant relationships and how to distinguish them.
Epigastric pain, nocturnal symptoms or previous ulcer bleeding makes active infection clinically consequential even when dyspepsia is mild.
Iron or vitamin B12 deficiency with corpus gastritis can accompany long-standing H pylori but also requires assessment for autoimmune gastritis.
Recent PPI, antibiotic or bismuth exposure can suppress bacterial load without eliminating infection.
Severe diarrhoea, rash, jaundice, arrhythmia symptoms or anaphylaxis during triple therapy requires urgent drug review.
A properly timed active test after two adherent courses should prompt specialist resistance-guided management rather than serial empirical repetition.
03Interpreting evidenceInformation, measurements and their limitations.
Consider the information, its meaning and its limitations before deciding what follows.
- 01
Carbon-13 urea breath test - Why
- Detect active urease-producing H pylori before treatment or at test of cure.
- Interpretation and limitations
- Confirm PPI and antibiotic washout; a negative result obtained during suppression may need repeat testing under valid conditions.
- 02
Validated laboratory monoclonal stool-antigen assay - Why
- Detect current infection or confirm eradication using a laboratory assay supported by modern diagnostic consensus.
- Interpretation and limitations
- Use a validated laboratory monoclonal assay, rather than assuming a rapid near-patient cassette has equivalent performance. Wait at least four weeks after antibiotics or bismuth and two weeks after PPIs; record those dates with the result.
- 03
Endoscopic biopsies - Why
- Diagnose infection while examining ulceration, atrophy or alarm symptoms.
- Interpretation and limitations
- Take samples from appropriate antral and corpus sites because patchy organisms and metaplastic mucosa can yield false-negative histology.
- 04
Culture or molecular resistance testing - Why
- Guide antibiotic selection after repeated eradication failure.
- Interpretation and limitations
- A resistance result is useful only when linked to the exact prior drugs, adherence and a regimen the patient can safely receive.
- 05
Full blood count, ferritin and B12 - Why
- Assess anaemia or micronutrient consequences when gastritis is extensive.
- Interpretation and limitations
- Correct deficiencies while treating the cause; isolated replacement does not resolve an ulcer or neoplastic risk.
04Applied reasoningWorked examples connecting principles to decisions.
01Worked case: valid test and verified cureRemove suppression before trusting the resultA 44-year-old with previous duodenal ulcer has persistent dyspepsia; a stool antigen test obtained while taking omeprazole was negative. His regular medicines include simvastatin; renal and hepatic function are normal.+
- 1Confirm that there are no alarm symptoms, stop omeprazole for two weeks and ensure no antibiotic or bismuth exposure occurred in the preceding four weeks.
- 2A carbon-13 urea breath test after the valid washout is positive, showing that the earlier on-treatment result was falsely negative.
- 3The allergy and prior-antibiotic history permits the licensed clarithromycin combination, QT and electrolyte checks are satisfactory, and pharmacy arranges suspension of simvastatin during the seven-day course because concomitant use is contraindicated. Give omeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg, each orally twice daily for seven days, with a written restart and adherence plan.
- 4At a correctly timed post-treatment review, repeat breath testing is negative and the patient confirms all 14 twice-daily doses were completed; document eradication and the plan if ulcer symptoms recur.
02Failure after one courseChange antibiotic pressureA validated laboratory monoclonal stool-antigen assay remains positive after a correctly timed test and documented adherence to clarithromycin-based triple therapy. The adult has no penicillin allergy, previous metronidazole exposure or relevant organ impairment.+
- 1Reconstruct doses, missed tablets, vomiting, previous antibiotic exposure and the exact timing of the test of cure.
- 2Apply NICE CG184 second-line selection: use the antibiotic not used first line. After confirming local susceptibility policy, prescribe omeprazole 20 mg, amoxicillin 1 g and metronidazole 400 mg, each orally twice daily for seven days. NHS Lothian supplies this dose combination; NICE supplies the post-clarithromycin-failure choice. Do not repeat clarithromycin empirically.
- 3Explain administration and adverse effects for all three medicines. The selected metronidazole tablet label supplies its safety checks; adult H pylori dosing here is guideline-supported rather than an adult eradication regimen listed in that product label. Avoid alcohol during treatment and for at least 48 hours afterwards; review warfarin, lithium and neurological or hepatic disease before starting.
- 4Retest under valid washout conditions and seek specialist susceptibility advice if a second complete course fails.
03Gastric ulcerLink eradication to mucosal healingGastroscopy finds a 20 mm gastric ulcer and biopsies identify H pylori without malignancy.+
- 1Treat H pylori with an explicit eradication regimen and provide full-dose acid suppression for ulcer healing.
- 2Review NSAIDs, aspirin, smoking and other drivers rather than assuming infection is the only cause.
- 3Repeat endoscopy six to eight weeks after treatment began, tailored to lesion size, and rebiopsy any unhealed or irregular area.
- 4Verify active-test eradication and histological healing before discharging the ulcer from follow-up.
05Relevant medicines and safetySpecific regimens and precautions where medicines are relevant.
Omeprazole, amoxicillin and clarithromycin eradication example
For a suitable adult, give omeprazole 20 mg orally twice daily, amoxicillin 1,000 mg orally twice daily and clarithromycin 500 mg orally twice daily for 7 days. Select this licensed example only when penicillin and macrolide exposure, allergy, interactions and current local resistance guidance permit it. Take the omeprazole capsule whole with water, using the morning and evening schedule for this twice-daily course; do not chew or crush the capsule or enteric-coated pellets. Swallow amoxicillin 500 mg capsules whole with water without opening them; food does not impair absorption. Clarithromycin film-coated tablets can be taken with or without food.Amoxicillin is contraindicated with any penicillin hypersensitivity or a previous severe immediate reaction to another beta-lactam. For the selected 500 mg capsule, GFR 10–30 mL/min permits at most 500 mg twice daily and GFR below 10 at most 500 mg daily; do not apply this normal-function 1 g twice-daily eradication schedule to those patients. Monitor hepatic disease and review methotrexate or warfarin interactions. Clarithromycin requires half-dose reduction at CrCl below 30 mL/min and is contraindicated in severe hepatic failure with renal impairment, previous QT prolongation or ventricular arrhythmia, and hypokalaemia or hypomagnesaemia. Do not coadminister simvastatin/lovastatin, colchicine, oral midazolam, domperidone, ticagrelor, ranolazine or other contraindicated CYP3A4/QT medicines in its label. Suspend the contraindicated statin during an essential clarithromycin course or select a compatible regimen. Omeprazole is contraindicated with nelfinavir; discourage concomitant clopidogrel. Renal impairment does not require omeprazole reduction, but hepatic impairment may need only 10–20 mg daily: the fixed example needs adjustment before use. Explain diarrhoea, candidiasis and allergy, and stop and assess serious hypersensitivity or severe persistent diarrhoea.
Alternative after clarithromycin failure: omeprazole, amoxicillin and metronidazole
For a suitable adult with no penicillin allergy or prior metronidazole exposure, give omeprazole 20 mg, amoxicillin 1 g and metronidazole 400 mg, all orally every 12 hours for seven days. This follows NICE second-line antibiotic selection and the NHS Lothian dose example, subject to local resistance advice. The selected metronidazole 400 mg film-coated tablet supplies product safety; this adult H pylori course is guideline-supported off-label use for that product. Swallow it with water without chewing, during or after food. Use the capsule administration and renal/hepatic qualifications in the preceding card for omeprazole and amoxicillin.Do not use metronidazole with nitroimidazole hypersensitivity; the amoxicillin beta-lactam contraindications still apply. Metronidazole itself needs no routine renal dose reduction, although dialysis removes it and requires post-haemodialysis redosing; this does not remove amoxicillin renal restrictions. In hepatic encephalopathy its label reduces total daily metronidazole to one-third, possibly once daily, so do not use this fixed tablet regimen unchanged: arrange a measurable adjusted formulation and specialist eradication plan. Avoid alcohol during the course and for at least 48 hours afterwards; monitor INR and adjust warfarin if needed. Arrange lithium taper/withdrawal with the prescriber before treatment and monitor lithium, creatinine and electrolytes if coadministration is necessary. Stop and review neurological toxicity or severe skin reactions. In Cockayne syndrome use only if no alternative and benefit outweighs risk, with liver tests before, during and after treatment. Review pregnancy, lactation, disulfiram and other interactions before prescribing.
06Checking understandingVerify the reasoning, revisit uncertainties and apply feedback.
- Record the exact pre-test PPI, antibiotic and bismuth washout rather than documenting only that a test was negative.
- Ask about every component and missed dose when assessing eradication failure.
- In peptic ulcer disease, arrange the NICE six-to-eight-week retest after treatment began. Use carbon-13 breath testing, or a validated laboratory monoclonal stool-antigen assay under the modern diagnostic consensus, with the documented two-week PPI and four-week antibiotic/bismuth washouts.
- Track repeat endoscopy and histology for gastric ulcer until healing or another diagnosis is established.
- Refer after two failed complete courses for resistance-aware specialist selection.
07Special situationsVariants, exceptions and circumstances that change the usual approach.
Serology cannot prove cure
Antibody concentrations can remain positive after bacteria have been eradicated, so use breath or stool antigen testing.
PPI washout is diagnostic treatment
Two weeks without acid suppression prevents a convenient but uninterpretable false-negative result.
Previous antibiotics predict failure
A history of macrolide exposure matters even when it was prescribed for a respiratory rather than gastric indication.
Gastric ulcer needs two answers
Successful eradication does not replace proof of ulcer healing and adequate exclusion of malignancy.
08Common pitfallsFrequent interpretation and management errors.
- 01
Testing stool antigen while the patient continues a PPI and accepting a negative result.
- 02
Prescribing “triple therapy” without dose, frequency, duration or interaction review.
- 03
Repeating clarithromycin after a documented clarithromycin-containing failure.
- 04
Using serology as the test of cure after eradication treatment.