For decades, a week or so of antibiotic therapy has been prescribed to successfully treat the cause of stomach ulcers. Alarmingly, though, the Helicobacter pylori (H. pylori) bacterium that causes ulcers is becoming resistant to the antibiotics. Good news: New guidelines show how to kill H. pylori in an era of increasing antibiotic resistance.

Since the 1990s, standard care for ulcers caused by H. pylori has been a treatment called triple therapy: Seven to 10 days of two different antibiotics—clarithromycin (Biaxin) and metronidazole (Flagyl) or amoxicillin—plus a proton pump inhibitor (PPI) antacid, such as esomeprazole (Nexium) or omeprazole (Prilosec). Initially, triple therapy was 90% effective against H. pylori. Now the bacterium is becoming resistant to the antibiotics, especially to clarithromycin and to levofloxacin, which is sometimes substituted for clarithromycin. To make matters worse, if one round of triple therapy doesn’t eradicate the H. pylori, doctors frequently prescribe additional rounds, exposing patients to more antibiotics.


To address what has become a worldwide concern, three expert groups—the European Helicobacter and Microbiota Study Group, the American College of Gastroenterology and the Canadian Association of Gastroenterology—separately developed their own guidelines for safer ways to treat H. pylori. Researchers from these three groups and from McGill University reviewed all three sets of recommendations and came up with a new set of guidelines that incorporates the key points from all three. Here is what they are…

First-line therapy: Instead of triple therapy, patients who have been diagnosed with H. pylori ulcers should start by taking bismuth quadruple therapy for 14 days—bismuth, two different antibiotics (metronidazole and tetracycline) four times daily plus a PPI antacid twice daily. Bismuth is a natural element and has been safely used since ancient times as a remedy for heartburn. It is, in fact, the main ingredient in Pepto-Bismol (which is sometimes the bismuth used in the therapy). Research shows that when given along with metronidazole, tetracycline and a PPI, it significantly inhibits H. pylori.

Second-line therapies: If the first treatment is not effective, the following can be tried… 

• For patients who have not previously been treated with metronidazole (for instance, because they were treated with triple therapy using amoxicillin instead), bismuth quadruple therapy for 14 days should be used. For patients who were treated with metronidazole but not with bismuth (because they were treated with a non-bismuth quadruple therapy), bismuth quadruple therapy can be used—preferably with levofloxacin substituted for metronidazole if the patient is not resistant to that antibiotic.

• If metronidazole is ruled out because of previous use, triple therapy substituting levofloxacin for clarithromycin (as long as the patient is not resistant to levofloxacin) should be given for 14 days.

And if those therapies fail to kill off H. pylori

• High-dose amoxicillin plus a PPI for 14 days.

• As a “last resort,” triple therapy substituting rifabutin (another antibiotic often used to treat tuberculosis) for clarithromycin for 10 days can be used. This therapy is reserved only for patients for whom multiple previous attempts have failed because of the potential for serious adverse side effects, such bone marrow suppression.

The new guidelines do not generally recommend probiotics during H. pylori treatment. Patients on ulcer therapies often take these to help reduce side effects from the medications, but evidence so far is weak for any benefit from probiotics—both for preventing side effects and for helping to treat the H. pylori. More research is needed to determine if specific strains of probiotics might help in still undetermined ways, and if so, how much to take.


The new guidelines don’t completely rule out triple therapy, but they advise that it should be limited to patients living in areas where local H. pylori resistance to clarithromycin is low (less than 15%). Since that is hard to know in the US—few people get the endoscopic testing to verify H. pylori, and unlike Europe, we don’t keep local resistance registries in this country—most US patients should stick to bismuth-quadruple first-line therapy. Note: The guidelines stipulate that triple therapy should be avoided for patients who have already had clarithromycin or other macrolide antibiotics, which include erythromycin and azithromycin.


As stool-based molecular tests become more advanced, it may become easier and cheaper to routinely test for antibiotic susceptibility to determine the best medication combination for each patient. If such testing were to become routine, it would also make it easier for regions to maintain a database of local rates of resistance to specific antibiotics—which would be invaluably helpful in global efforts to address antibiotic resistance. Another treatment option that may become more widely available is a more powerful and longer-lasting antacid called vonoprazan, a potassium-competitive acid blocker (PCAB), that is now being used in Japan. Clinical trials have shown that when used in triple therapy, it is more effective than PPIs against H. pylori.

H. pylori infection is a common infection mainly acquired in childhood, although the likelihood of having it increases with age. The bacterium is found in about 20% of 40-year-olds and 50% of people over age 60. However, why only some people with the infection develop stomach ulcers while most do not is not known. H. pylori also causes more than 80% of stomach cancer cases, the third most common cause of cancer deaths worldwide.

The symptoms to watch for include gnawing or burning stomach pain that may last for minutes or hours…tends to be worse in the morning or on an empty stomach…and may be relieved by eating or taking an antacid. Diagnosis usually starts with a blood or breath test to determine if you have H. pylori.

If it turns out that you do have stomach ulcers, discuss these new guidelines with your doctor. Even if you don’t have ulcer symptoms, if you areat high risk for stomach cancer—for instance because of family history—it’s a good idea to be tested for H. pylori and treated if you have the bacterium.