H pylori: ACG Guideline Advises New Approaches to Treatment

Helicobacter pylori is one of the most common human bacterial chronic infections globally. Its prevalence has actually decreased in North America in recent years, although its current range of approximately 30%-40% remains substantial given the potential clinical implications of infection. 
Standards have changed considerably regarding the testing, treatment, and follow-up of H pylori. This is made clear by the just-published clinical practice guideline from the American College of Gastroenterology (ACG), which provides several new recommendations based on recent scientific evidence that should change your clinical approach to managing this common infection. 
This discussion aims to synthesize and highlight key concepts from the ACG’s comprehensive publication. 
The cardinal diseases caused by H pylori have traditionally included peptic ulcer disease, marginal zone B-cell lymphoma, gastric adenocarcinoma, and dyspepsia. 
Additional associations have been made with idiopathic thrombocytopenic purpura and otherwise unexplained iron deficiency. 
New evidence suggests that patients taking long-term nonsteroidal anti-inflammatory drugs, including low-dose aspirin, are relatively more susceptible to infection. 
The ACG’s guideline also recommends testing persons at an increased risk for gastric adenocarcinoma (eg, those with autoimmune gastritis, current or history of premalignant conditions, or first-degree relative with gastric cancer), as well as household members of patients with a positive nonserologic test for H pylori.
The authors note that those with an indication for testing should be offered treatment if determined to have an infection. These patients should also undergo a posttreatment test-of-cure, which should occur at least 4 weeks afterwards using a urea breath test, fecal antigen test, or gastric biopsy. 
Patients with H pylori infections are advised to undergo treatment for a duration of 14 days. Some of the commercial prepackaged H pylori treatment options (eg, Pylera, which contains bismuth subcitrate/metronidazole/tetracycline) are dispensed in regimens lasting only 10 days and currently are viewed as inadequate.
In the United States, the patterns of antibiotic resistance for the previously used standard drugs in the treatment of H pylori have increased considerably. They range from 32% for clarithromycin, 38% for levofloxacin, and 42% for metronidazole, in contrast to 3% for amoxicillin, 1% for tetracycline, and 0% for rifabutin. 
Clarithromycin- and levofloxacin-containing treatments should be avoided in treatment-naive patients unless specifically directed following the results of susceptibility tests with either a phenotypic method (culture-based) or a molecular method (polymerase chain reaction or next-generation sequencing). Notably, the mutations responsible for both clarithromycin and levofloxacin resistance may be detectable by stool-based testing.
Maintenance of intragastric acid suppression is key to H pylori eradication, as elevated intragastric pH promotes active replication of H pylori and makes it more susceptible to bactericidal antibiotics. 
Therefore, the use of histamine-2 receptors is not recommended, as they are inadequate for achieving acid suppression. Instead, a dual-based therapy of either the potassium-competitive acid blocker (PCAB) vonoprazan (20 mg) or a high-dose proton pump inhibitor (PPI) and amoxicillin, administered twice daily, is effective, although this finding is based on limited evidence. 
In treatment-naive patients without penicillin allergy and for whom antibiotic susceptibility testing has not been obtained, the guideline offers its strongest recommendation for bismuth quadruple therapy. This therapy typically consists of a PPI, bismuth subcitrate or subsalicylate, tetracycline, and metronidazole. 
Among those with a penicillin allergy, bismuth quadruple therapy is also the primary treatment choice. The authors suggest that patients with a suspected allergy are referred to an allergist for possible penicillin desensitization, given that less than 1% of the population is thought to present with a “true” allergy.
The guideline also presented conditional recommendations, based on low- to moderate-quality evidence, for using a rifabutin-based triple regimen of omeprazole, amoxicillin, and rifabutin (Talicia); a PCAB-based dual regimen of vonoprazan and amoxicillin (Voquezna Dual Pak); and a PCAB-based triple regimen of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak). In patients with unknown clarithromycin susceptibility, the PCAB-based triple therapy is preferred over PPI-clarithromycin triple therapy.
Although probiotics have been suggested to possibly lead to increased effectiveness or tolerability for H pylori eradication, this was based on studies with significant heterogeneity in their designs. At present, no high-quality data support probiotic therapy.
Clinicians may substitute doxycycline for tetracycline due to availability or cost, and also may prescribe metronidazole at a lower dose than recommended (1.5-2 g/d) to limit side effects. Both modifications have been associated with lower rates of H pylori eradication and are not recommended.
Quadruple bismuth therapy is the optimal approach among treatment-experienced patients with persistent H pylori infection who have not previously received this therapy. However, this recommendation was rated as conditional, given that it was based on a low quality of evidence. 
The guideline offered other recommendations for treatment-experienced patients with persistent infection who had received bismuth quadruple therapy — also conditionally based on a low quality of evidence. 
In such patients, it is recommended to consider the use of a rifabutin-based triple therapy (ie, a PPI standard to double dose, amoxicillin, and rifabutin) and a levofloxacin-based triple therapy (ie, a PPI standard dose, levofloxacin, and amoxicillin or metronidazole). 
Although significant evidence gaps prevented the authors from providing formal recommendations, they included a PCAB-based triple therapy of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak) and a high-dose dual therapy of either vonoprazan (20 mg) or PPI (double dose) and amoxicillin among their suggested salvage regimens for these patients.
The ACG’s excellent clinical guideline offers new standards for clinicians involved in the diagnosis and treatment of H pylori. 
We must recognize, however, that there are still substantial evidence gaps, particularly around the use of a PCAB-based regimen and its relative advantages over a standard or high-dose PPI-based regimen. This may be of particular importance based on the variable prevalence of cytochrome P450 2C19 (CYP2C19) polymorphisms in the specific patient populations, as PCABs are not metabolized by CYP2C19. 
Reviewing the entirety of the ACG’s clinical guideline is encouraged for additional details about the management of H pylori beyond what is highlighted herein.
David A. Johnson, MD, a regular contributor to Medscape, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease.