New German Guideline for H. pylori Infection Coming Soon

Angela Speth, MD

June 09, 2022

The updated German guideline for Helicobacter pylori therapy is expected to be published in June or July. Unlike the previous version, it will state for the first time that experts recommend an infection be treated as soon as it is detected, regardless of whether the patient has symptoms.

Furthermore, they offer guidance in a landscape of rapidly changing antibiotic resistance. For an empirical approach (that is, if the bacterial response to antibiotics has not been tested), they recommend bismuth quadruple therapy.

"One important new feature in the revised H. pylori guideline is that a gastric infestation is principally defined as an infectious disease in accordance with international guidelines," guideline coordinator Christian Schulz, MD, deputy clinical director at the Ludwig Maximilian University of Munich, Germany, told Medscape Medical News. "Consequently, it is now recommended to always derive an action from the diagnosis."

Dangerous Without Symptoms

"Mind you, this means no screening, but as soon as the pathogen is detected, an eradication should always follow, even if it is barely causing any discomfort," Schulz added. It is estimated that a third of Germany's population is a carrier of the gastric bacteria H. pylori.

With the new specifications, the guideline is based on the 2016/17 European Maastricht V/Florence Consensus. "This is globally the most read and cited publication on the symptoms, diagnosis, therapy, and prevention of H. pylori infection," said Schulz.

The reason for the urgent therapy indication is to protect against serious complications such as gastritis, ulcers, lymphomas, and gastric cancer. For example, approximately 90% of gastric cancer cases are associated with H. pylori. Antibiotic treatment reduces the rate of gastric cancer by approximately one third, compared with patients who are not treated.

Publication Is Imminent

The German guideline was last revised in 2016, and a new version was therefore due. The new guideline was open for comment until April 11, 2022, in accordance with the Association of the Scientific Medical Societies in Germany (AWMF) regulations. Gastroenterologists were able to point out ambiguities or omissions and suggest corrections during the consultation phase. The final edition is in progress.

Which algorithm is being used to guide physicians through the treatment options? This is a crucial question because the ever-broadening resistance to antibiotics has been a cause for concern for some time now. For example, the rate at which pathogens resist elimination can be seen in a costly network meta-analysis with therapy studies from 1998 to 2019.

Changing Data

"Even if published just a year ago, at least some parts of it have already been revised. Today, the course is laid out differently," said Schulz. "We have discussed the results for the new guidelines, especially because lots of authors were also a part of that team that was involved in the Maastricht consensus."

A network analysis makes it possible for multiple therapies to be compared in direct and indirect pairings. Theodoros Rokkas, MD, director of the Henry Dunant Hospital Center in Athens, Greece, and colleagues examined 68 randomized studies with a total of about 23,000 patients from across the globe. By forming 28 pairs of regimens from the eight empirical regimens tested, they created a hierarchy of effectiveness.

Levofloxacin Outdated

Significant regional differences were revealed. While triple therapy with the acid blocker vonoprazan was the favorite in East Asia, the only place where it is approved, levofloxacin triple therapy performed the best in Western and West Asian countries, where it was associated with eradication rates of 91% and 89%, respectively. However, the new guideline no longer recommends it because the pathogens respond to it less now.

The temporal differences were interesting, which, in the opinion of Rokkas and colleagues, reflects the growing infestation of resistant strains of H. pylori. Before 2010, eradication with clarithromycin triple therapy had a much better success rate than in subsequent years.

Just like the experts for the European and German guideline, they therefore do not consider empirical therapies examined using a "trial and error" approach an ideal. A customized strategy according to the principle of antimicrobial stewardship, also known as an "antibiotic susceptibility-guided" strategy, ultimately yields higher eradication rates, often at a lower cost. This means that it would be best to first test the sensitivity of H. pylori against a range of antibiotics and then prescribe the most effective.

Biopsies Required

As Schulz explained, there are two types of resistance tests. In the phenotypical method, an agar plate is inoculated with bacteria from a biopsy and slices with antibiotics are applied. The diameter of the inhibition zone allows conclusions to be drawn about the response. "The upcoming guideline explicitly recommends using samples for this that were collected for the diagnostics," said Schulz.

In genotypical procedures, the polymerase chain reaction quickly and directly searches for the pathogen's resistance genes, especially against clarithromycin, levofloxacin, tetracycline, and rifampicin. More recent techniques allow these tests also to be performed on stool samples, which means that a gastroscopy with biopsy need only be performed if there is a corresponding indication for it.

Probatory Therapies Common

However, the tests are expensive and not possible everywhere, or there are no tissue samples because detection was made in 13C in the breath or stool antigens, for example in patients with dyspepsia. "The empirical approach prevails in daily practice," said Schulz. "You have to consider that in Germany it really is a state of luxury when compared with some European and above all African countries, such as Nigeria."

The guideline specifies that if you do deviate to an empirical therapy, you absolutely must know the state of resistance in the region concerned. This principle is particularly applicable for clarithromycin, a component of triple therapy that has long formed the standard, perhaps together with pantoprazole plus either amoxicillin or metronidazole for 14 days.

The cutoff is set at a clarithromycin resistance of 15%:

  • If the rate is lower, then this antibiotic can be used.

  • However, at higher values, the new guideline recommends a bismuth quadruple regimen: proton pump inhibitor plus bismuth salt plus metronidazole plus tetracycline.

Clarithromycin Regionally Limited

The problem is, however, that hardly anyone knows the prevalence of clarithromycin resistance, especially because it is constantly changing and trending upward. "In this case, this antibiotic is avoided. Instead, the case is handled as if the prevalence was above 15%, and the bismuth combination is also chosen for 10 days," said Schulz.

The fact that the resistance rate of possible alternatives in Germany is high (up to 20% for clarithromycin and even up to 40% for metronidazole) supports extensive first-line use.

In contrast, bismuth does not appear to elicit a defense mechanism in H. pylori, but instead can overcome possible resistance to metronidazole, because both substances work synergistically, explains Schulz in an article in Der Internist. Very high healing rates are achieved in this way.

New Acid Blockers

But a new treatment, vonoprazan, could get things moving in the muddled situation of antibiotic resistance. Rokkas and his working group established eradication rates of more than 90% for empirical triple therapies in which a conventional proton pump inhibitor was replaced by vonoprazan, a potassium-competitive acid blocker. "The data are hopeful," said Schulz. "The potential is there for dual therapy, vonoprazan plus amoxicillin, to experience a revival."

Vonoprazan has several advantages. It can withstand the low pH value in the stomach with high stability and therefore fulfill its task effectively. Because it suppresses acid formation so well, it also prolongs the bioavailability of acid-susceptible antibiotics. A more neutral environment fosters the reproduction of bacteria; in doing so, it brings them into a more sensitive phase of replication in which they can be easily attacked by antibiotics.

However, vonoprazan is currently only available in a few Asian countries such as Japan and not yet in Europe and the United States. "The application has been submitted to the FDA," said Schulz. "Now the additional benefits compared to the conventional proton pump inhibitors, which are also very effective, must be proven. A manufacturer must also be found. Production just for the sake of eradication treatment is unlikely to be worthwhile for a company."

This article was translated from the Medscape German edition.

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