Key points
- Before deciding that Helicobacter pylori treatment has failed, check that the test was done properly: at least 4 weeks without antibiotics and 2 weeks without omeprazole.2
- A blood test (serology) cannot confirm cure. The breath test or the stool antigen test must be used.2
- The VI Spanish Consensus Conference (2026) requires treatments to cure around 90% of patients or more, so it recommends quadruple regimens both first-line and as rescue.1
- The same treatment is not repeated. After a clarithromycin regimen, bismuth quadruple therapy (Pylera®) is recommended; after Pylera®, a levofloxacin and bismuth quadruple regimen.1
- After three failures, whether to keep trying is carefully reassessed and, if so, a fourth-line rifabutin regimen is considered.1
This article summarises the evidence and clinical guidelines so you can understand your situation. It does not replace an individual assessment.
You have taken the Helicobacter pylori treatment, put up with days of tablets and side effects, and the follow-up test is still positive. It is a very common situation and, understandably, a disheartening one.
Before treating again there are two questions to answer: is the result reliable, and why did it fail? With those answers, and following the recommendations of the VI Spanish Consensus Conference published in 2026, the chance of being cured with the next treatment is very high.1
Why eradicating it is worthwhile
Helicobacter pylori is a bacterium that infects the stomach, usually from childhood, and can stay there for life. It affects around half of the world’s population, including Spain, and is the main cause of chronic gastritis, stomach and duodenal ulcers and stomach cancer.1 That is why treating everyone in whom it is diagnosed is recommended, and always confirming afterwards that it has gone.1,2
First: check that the result is reliable
Before assuming the treatment has failed, it is worth ruling out something that happens more often than you might think: the follow-up test was not done properly.
| Condition | Why it matters |
|---|---|
| At least 4 weeks after finishing antibiotics or bismuth | Before then the bacterium may be suppressed but not eliminated, and the result can mislead |
| Omeprazole or other acid-suppressing drugs stopped 2 weeks before | They reduce the number of bacteria and can give a false negative |
| Use the breath test or stool antigen test | These are the valid tests to confirm cure |
| Do not use serology (a blood test) | Antibodies remain positive long after cure |
Before declaring a treatment failed
Check how long passed between the end of treatment and the test, whether you were taking omeprazole and what type of test you had. It is the first thing I review in clinic, and it resolves a proportion of cases without treating again.
Why treatment really fails
When the result is reliable, the causes are fairly specific:
- Antibiotic resistance, especially to clarithromycin. This is why classic triple therapy is no longer recommended and why the new consensus prioritises a regimen that depends less on that resistance.1
- Ineffective regimens. In the European Helicobacter pylori registry, with more than 21,000 patients, classic triple therapy did not achieve acceptable cure rates, whereas quadruple regimens did.4 The Spanish consensus now requires curing around 90% of patients or more.1
- Too low a dose of acid suppression. The consensus recommends giving quadruple regimens with a high dose, equivalent to omeprazole 40 mg every 12 hours.1
- Not completing the treatment. Side effects are common and patients are not always warned. Stopping after a few days is almost the same as not taking it.
- Having taken those antibiotics before. A course of clarithromycin or levofloxacin for a chest infection years ago may have selected resistant bacteria.2
Which treatment is recommended in Spain today
The VI Spanish Consensus Conference, published in 2026 and endorsed by the Spanish Association of Gastroenterology and the Spanish Society of Digestive Pathology, has changed the order of preference of treatments:1
- First choice: bismuth quadruple therapy, combining an acid suppressant with a capsule containing bismuth, tetracycline and metronidazole (Pylera®), for 10 days. It is also the regimen of choice for people allergic to penicillin, because it contains no amoxicillin.
- Alternatives, when Pylera® cannot be used or is unavailable: non-bismuth concomitant quadruple therapy (acid suppressant, amoxicillin, clarithromycin and metronidazole) for 14 days, or an acid suppressant with amoxicillin, clarithromycin and bismuth for 14 days.
| Regimen | Components | Duration |
|---|---|---|
| Bismuth quadruple therapy (Pylera®) | Acid suppressant + bismuth, tetracycline and metronidazole (in a single capsule) | 10 days |
| Non-bismuth concomitant quadruple therapy | Acid suppressant + amoxicillin + clarithromycin + metronidazole | 14 days |
| Clarithromycin and bismuth quadruple therapy | Acid suppressant + amoxicillin + clarithromycin + bismuth | 14 days |
| Levofloxacin and bismuth quadruple therapy | Acid suppressant + amoxicillin + levofloxacin + bismuth | 14 days |
| Rifabutin regimen | Acid suppressant + amoxicillin + rifabutin + bismuth | 10-12 days |
The consensus also states that age alone should not change the choice: older people respond to and tolerate these treatments as well as younger people, unless allergies, interactions or health problems require an individual approach.1
What to do after a failure
The rule is simple and constantly broken: the same treatment is not repeated. Rescue treatment is chosen according to the antibiotics already used.1,2 That is why, when someone comes to clinic for this reason, the first thing I ask for is the exact details: which antibiotics, at what dose and for how many days. It is information almost nobody brings, because almost nobody has been asked for it.
| Treatments that have already failed | Rescue recommended by the VI Spanish Consensus |
|---|---|
| One clarithromycin regimen (triple or concomitant) | Bismuth quadruple therapy (Pylera®). If it cannot be used: levofloxacin and bismuth quadruple therapy |
| Pylera® | Levofloxacin and bismuth quadruple therapy (acid suppressant, amoxicillin, levofloxacin and bismuth) |
| Clarithromycin, then levofloxacin | Pylera® |
| Clarithromycin, then Pylera® | Levofloxacin and bismuth quadruple therapy |
| Pylera®, then levofloxacin | Non-bismuth concomitant quadruple therapy, or an acid suppressant with amoxicillin, clarithromycin and bismuth |
| Three treatments | Reassess whether to continue; if so, fourth-line rifabutin regimen |
After a clarithromycin failure, the consensus prefers Pylera® to levofloxacin because its effectiveness is more consistent, it depends less on resistance and it avoids fluoroquinolones, which carry safety warnings.1
If you are allergic to penicillin
Amoxicillin cannot be used and the options change: Pylera® is the first-line treatment and also the rescue after a clarithromycin and metronidazole regimen. If Pylera® fails, the consensus suggests an acid suppressant with levofloxacin, clarithromycin and bismuth.1 It is also worth confirming whether the allergy is real, because many are not.3
How to take the treatment so that it works
Some failures are due not to the bacterium but to the treatment not being completed. That is why the new consensus recommends explaining the regimen to the patient in detail and preferably in writing: how to take it, for how many days, why it must be finished and which side effects to expect.1
| What may happen | Is it normal? | What to do |
|---|---|---|
| Black stools with bismuth-containing regimens | Yes, it is an effect of bismuth | It does not mean bleeding if you feel well. If you also feel dizzy or weak, or vomit blood, go to A&E |
| A metallic taste in the mouth | Very common | It goes away when the treatment ends |
| Mild diarrhoea or nausea | Common | Keep hydrated and continue; seek advice if diarrhoea is severe, bloody or with fever |
| Skin rash, intense itching or facial swelling | No | Stop the treatment and seek advice immediately: it may be an allergy |
- Take every dose at the times indicated and for all the prescribed days, even if you feel better earlier.
- With Pylera®, the consensus accepts splitting the same daily dose into three doses instead of four, with equal effectiveness, which makes it easier to follow.1
- Pylera® contains tetracycline: avoid taking it with milk or dairy products, which reduce its absorption.
- If you had many side effects with previous treatments, ask about adding a probiotic (particularly Saccharomyces boulardii), which may improve tolerance.1
- If a side effect makes you think about giving up, call before stopping: there is almost always a solution.
When two or three treatments have failed
After two failures, the Spanish consensus proposes a third-line regimen chosen according to the sequence of antibiotics already received (see the table above).1
After a third failure, the recommendation is to carefully reassess whether it is worth continuing, weighing the expected benefit against possible safety issues. If the decision is to continue, a fourth-line rifabutin regimen is considered, with close monitoring.1
For some patients it is right to keep trying; for others, follow-up. Age, symptoms, family history of stomach cancer and gastroscopy findings all count. What makes no sense is chaining courses of antibiotics without a plan.
Confirmation is not optional
Every treatment must be confirmed with a later test, respecting the time limits. The new consensus recommends this systematically for every treated patient.1
Common myths
“I had a blood test after treatment and I am still positive.”
Serology cannot confirm cure: antibodies persist for a long time. The breath test or stool antigen test must be used.2
“If I feel well, I am cured.”
Symptoms do not show whether the bacterium has gone. The follow-up test is always needed.1
“It is best to repeat the same treatment.”
Repeating the same antibiotics has little chance of success and encourages resistance. Rescue is chosen according to what has already been taken.1
“Probiotics increase the cure rate.”
With current quadruple regimens they do not improve effectiveness, and the consensus does not recommend them routinely. They may improve tolerance in people who had side effects.1
“At my age I need a milder treatment.”
Age alone does not change the treatment: older people respond to and tolerate it as well as younger people.1
“A special diet is needed to cure it.”
Diet does not affect eradication. What matters is the right regimen and completing it.
Warning signs: do not wait
These symptoms require a gastroscopy
If, as well as Helicobacter pylori, you have any of the following, treatment is not enough: the stomach needs to be examined.
- Vomiting blood, or black stools not explained by bismuth (go to A&E)
- Difficulty swallowing
- Unintentional weight loss
- Anaemia or iron deficiency
- Persistent vomiting
- New digestive symptoms from the age of 50-55
- A family history of stomach cancer
How I approach it in clinic
I will ask you to bring everything you have: reports, prescriptions or even the boxes of previous treatments. With that I reconstruct which antibiotics you have taken, at what dose and for how long, and review how and when the follow-up tests were done.
If the failure is real, I choose the rescue treatment recommended by the VI Spanish Consensus for your treatment history and allergies, and give it to you in writing, with the time of each dose, the side effects to expect and what to do about them. We book the follow-up test at the right time. If there are warning symptoms or several failures, we consider a gastroscopy.
Have you had one or more treatments and are still positive?
We review your case from the start before treating again, so that the next treatment is the last.
Frequently asked questions
How long do I need to wait before the follow-up test?
At least 4 weeks after finishing treatment, with omeprazole or other acid suppressants stopped for the 2 weeks before.2
I have heartburn and need something before the test. What can I take?
Simple antacids or alginates do not interfere with the test. Discuss it with your doctor.
Do I need to keep taking omeprazole after the treatment?
It depends. If you had an uncomplicated duodenal ulcer and do not take anti-inflammatories, aspirin or anticoagulants, it is not needed. If it was a stomach ulcer, continuing it for another 4 to 8 weeks is recommended.1
Is Helicobacter pylori contagious?
It is mainly transmitted in childhood, within the family. In adults, reinfection after cure is uncommon.
Can I drink alcohol during treatment?
It is better to avoid it, particularly if the regimen includes metronidazole, and because it worsens how well the treatment is tolerated.
References
- Gisbert JP, Alcedo J, Amador J, et al. VI Spanish Consensus Conference on the treatment of Helicobacter pylori infection. Gastroenterol Hepatol. 2026 (in press; Spanish edition, also published in English). Publication
- Malfertheiner P, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022. PubMed
- Chey WD, et al. ACG Clinical Guideline: Treatment of Helicobacter pylori infection. Am J Gastroenterol. 2024. PubMed
- Nyssen OP, et al. European Registry on Helicobacter pylori management (Hp-EuReg): patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients. Gut. 2021. PubMed
Links go to PubMed or the original publication and open in a new tab.
Related reading
Dr Fernando Casals Seoane
Consultant gastroenterologist with a PhD in Medicine from the Autonomous University of Madrid. He has worked at La Princesa University Hospital since 2009 and sees private patients at Ruber Juan Bravo Hospital. Certified by the European Board of Gastroenterology and Hepatology and honorary lecturer at the UAM. Principal investigator in international clinical trials on acute pancreatitis, including WATERFALL (NEJM, 2022).
Transparency: this article is not sponsored and does not promote any product or brand. All sources are linked.