What are the latest guideline recommendations for the treatment of Helicobacter pylori infection in the U.S.?

Background
Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that inhabits the mucus lining of the human stomach.^1,2 While many bacteria cannot survive in the acidic environment of the stomach, H. pylori can neutralize the acidity of its local environment in the stomach.² Additionally, H. pylori burrows into the mucus layer and adheres to the cells that line the stomach’s inner surface, allowing the bacterium to evade immune detection. H. pylori also disrupts local immune responses, making them ineffective in eliminating the organism.

H. pylori is one of the most common chronic bacterial infections in the world, with the Centers for Disease Control and Prevention (CDC) estimating that about two-thirds of the global population is infected, particularly in developing countries.^2,3 H. pylori is present in 30% to 40% of the North American population.⁴ Prevalence in the United States is higher among non-White racial and ethnic groups, among individuals living in crowded or unsanitary conditions, and among early generation immigrants from countries where H. pylori is endemic.

Transmission of H. pylori mainly occurs through oral contact with stool, saliva, or vomit.² Infection is typically acquired in early childhood, persists without treatment, and is a major cause for gastritis, peptic ulcers, gastric lymphoma, and gastric carcinoma.¹ Although the infection is usually asymptomatic, symptoms manifest in individuals with peptic ulcer disease and gastritis, often presenting as gnawing or burning epigastric pain.³ Other less common symptoms include loss of appetite, nausea, and vomiting. The World Health Organization has classified H. pylori as a carcinogen, and it is the strongest known risk factor for non-cardia gastric adenocarcinoma. Individuals infected with the bacteria have a 2- to 6-fold increased risk of developing gastric cancer and mucosa associated-lymphoid-type lymphoma compared to those without the infection.

Updated American College of Gastroenterology recommendations for H. pylori treatment
Recognizing the serious health risks of H. pylori, the American College of Gastroenterology (ACG) published an updated guideline in 2024 on the treatment of H. pylori infection in North America.⁴ The ACG notes that its recommendations have changed substantially from the previous guideline issued in 2017. Changes were prompted by increasing use of antibiotic susceptibility testing, rising resistance rates to antibiotics commonly used for treatment (e.g., clarithromycin, levofloxacin), and recent data on treatment regimens featuring new antibiotic options (i.e., rifabutin) and more potent gastric acid-suppressants (i.e., vonoprazan). Approvals of these newer agents/regimens are briefly discussed below.

Talicia^® (rifabutin, omeprazole, and amoxicillin) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of H. pylori infection in 2019.⁵ Approval was based on findings from two phase 3 trials (ERADICATE Hp and ERADICATE Hp2) involving H. pylori-positive adults complaining of epigastric pain/discomfort.^5-7 ERADICATE Hp compared Talicia^® to placebo, while ERADICATE Hp2 compared Talicia^® to omeprazole plus amoxicillin. Eradication of H. pylori following 14 days of treatment, the primary endpoint, favored Talicia^® in both studies.

Vonoprazan, a potassium-competitive acid blocker (PCAB), was FDA-approved for the treatment of H. pylori infection in 2022, and vonoprazan-containing regimens (Voquezna DualPak^® and Voquezna TriplePak^®) became available in December 2023.^4,8 Approval was based on the phase 3 PHALCON-HP trial which found that vonoprazan-based regimens were superior to proton pump inhibitor (PPI)-clarithromycin triple therapy in the overall study population of treatment-naïve adults with H. pylori infection and in the subgroup of patients with clarithromycin-resistant strains.⁹

The 2017 ACG guideline had recommended PPI-clarithromycin triple therapy as the primary treatment of H. pylori.¹⁰ Although H. pylori resistance to clarithromycin is increasing and treatment success with these regimens is decreasing, more than half of individuals in the U.S. with H. pylori infection continue to receive clarithromycin-based treatment regimens.¹¹ Therefore, the 2024 ACG guideline reinforces the importance of using non-clarithromycin-based regimens for the initial and salvage treatment of H. pylori infection.⁴

Tables 1 and 2 outline currently recommended regimens for treatment-naïve and treatment-experienced patients with H. pylori infection, respectively.⁴ The ACG recommends optimized bismuth quadruple therapy (BQT) for 14 days as the preferred regimen for treatment-naïve patients for whom antibiotic susceptibility is unknown. Empiric alternative regimens for patients without a penicillin allergy include rifabutin triple therapy or vonoprazan dual therapy for 14 days. For treatment-experienced patients with persistent H. pylori infection, optimized BQT for 14 days is again the preferred regimen for those who have not previously received BQT and for whom antibiotic susceptibility is unknown, or for those who failed to eradicate the infection with initial PPI-clarithromycin triple therapy. In patients previously treated with optimized BQT, rifabutin triple therapy is a suitable empiric alternative. Clarithromycin- or levofloxacin-containing salvage regimens should only be used if antibiotic susceptibility has been confirmed. For treatment-experienced patients with persistent H. pylori infection confirmed to be clarithromycin-sensitive, PPI- or PCAB-clarithromycin triple therapy is suggested.

The updated guideline states the incremental benefit of choosing an eradication regimen based on the antibiotic susceptibility profile, as opposed to empirically selecting a therapy, has not been fully defined or studied for both treatment-naive and treatment-experienced patients.⁴ It is advised to perform antibiotic susceptibility testing when the optimal therapy choice is uncertain, considering factors such as the patient’s previous H. pylori treatments, general antibiotic use history, and any documented penicillin allergy. Additionally, the ACG emphasizes that proof of H. pylori eradication using a fecal antigen test, urea breath testing, or gastric biopsy is required in all patients ≥4 weeks after completion of treatment.

Treatment challenges and considerations
Effective eradication of H. pylori is dependent on patient adherence to the treatment regimen, which may be hindered by insufficient education and poor management of side effects.⁸

While optimized BQT is the preferred H. pylori treatment option, adherence to this regimen can be challenging due to its complexity (4 drugs taken up to 4 times per day from separate pill bottles) and potential side effects like dyspepsia and altered bowel habits.¹² Additionally, intermittent shortages of tetracycline have been reported, and the ACG recommends against substituting the drug with doxycycline. In such situations, PCAB-based dual therapy with vonoprazan and amoxicillin may offer better compliance (due to its “bubble” packaging) and a more favorable side effect profile, although the cost may be higher. Regardless of the regimen used, patient education is critical for improving treatment compliance and successfully eliminating the infection.⁸ A 2022 meta-analysis found that improving patient education, for example, through phone calls, direct reminders via messaging apps, and additional materials like leaflets and charts, resulted in increased adherence and higher eradication rates in patients with H. pylori.¹³

Summary and Conclusion
Successful eradication of H. pylori requires a strategic, multi-faceted approach that focuses on selecting the appropriate therapy and ensuring patient adherence.⁸ Treatment selection is influenced by factors including, but not limited to, antibiotic susceptibility, prior antibiotic use, and patient preferences. The 2024 ACG guideline introduces significant updates from the previous recommendations due to increasing resistance to clarithromycin and levofloxacin, which have lowered the effectiveness of standard treatments.⁴ Changes in recommendations also reflect recent studies since 2017 that demonstrated the effectiveness of rifabutin-based triple therapy and vonoprazan-based treatments. The new guideline also stresses the importance of confirming H. pylori eradication after treatment and the role of antimicrobial susceptibility testing in managing the infection.

Optimized BQT is now recommended as first-line therapy in treatment-naive patients and in certain treatment-experienced patients with persistent infection.⁴ To ensure optimal H. pylori treatment, the guideline authors emphasize the need for randomized controlled trials conducted in North America comparing optimized BQT with rifabutin-based triple therapy and/or vonoprazan-based dual/triple therapy in both treatment-naïve and treatment-experienced patients. Implementation research is also important to reduce the continued use of PPI-clarithromycin triple therapy.¹² Lastly, the ACG suggests that future research should focus on antibiotic resistance patterns and outcomes to enable more targeted, evidence-based treatments.⁴ The proposal for a national registry to monitor H. pylori resistance rates highlights the importance of extensive data collection to improve treatment strategies.

References

1. Parikh NS, Ahlawat R. Helicobacter Pylori. In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 8, 2023.
2. Helicobacter pylori (H. pylori) and cancer. National Cancer Institute. April 12, 2023. Accessed December 13, 2024. https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/h-pylori-fact-sheet
3. Connor B. Helicobacter pylori. CDC Yellow Book 2024. Centers for Disease Control and Prevention. Accessed December 13, 2024. https://wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/helicobacter-pylori
4. Chey WD, Howden CW, Moss SF, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2024;119(9):1730-1753. doi:10.14309/ajg.0000000000002968
5. Talicia. Package insert. RedHill Biopharma Inc; 2024.
6. Kalfus IN, Graham DY, Riff DS, Panas RM. Rifabutin-containing triple therapy (RHB-105) for eradication of Helicobacter pylori: randomized ERADICATE Hp Trial. Antibiotics (Basel). 2020;9(10):685. doi:10.3390/antibiotics9100685
7. Graham DY, Canaan Y, Maher J, Wiener G, Hulten KG, Kalfus IN. Rifabutin-based triple therapy (RHB-105) for Helicobacter pylori rradication: a double-blind, randomized, controlled trial. Ann Intern Med. 2020;172(12):795-802. doi:10.7326/M19-3734
8. Cumber J, Rushing N, Castillo S, et al. Advancements and challenges in H pylori management. U.S. Pharma. 2024;49(4):21-25. Accessed December 13, 2024. https://www.uspharmacist.com/article/advancements-and-challenges-in-h-pylori-management
9. Chey WD, Mégraud F, Laine L, López LJ, Hunt BJ, Howden CW. Vonoprazan triple and dual therapy for Helicobacter pylori infection in the United States and Europe: randomized clinical trial. Gastroenterology. 2022;163(3):608-619.
10. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017;112(2):212-239. doi:10.1038/ajg.2016.563
11. Moss SF, Shah SC, Tan MC, El-Serag HB. Evolving concepts in helicobacter pylori management. Gastroenterology. 2024;166(2):267-283. doi: 10.1053/j.gastro.2023.09.047
12. Schoenfeld P. ACG guideline on treatment of Helicobacter pylori: new recommendations… will practice change? American College of Gastroenterology. September 17, 2024. Accessed December 13, 2024. https://gi.org/journals-publications/ebgi/schoenfeld_sep2024/
13. Zha J, Li YY, Qu JY, Yang XX, Han ZX, Zuo X. Effects of enhanced education for patients with the Helicobacter pylori infection: A systematic review and meta-analysis. Helicobacter. 2022;27(2):e12880. doi:10.1111/hel.12880

Prepared by:
Honey Joseph, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy

January 2025

The information presented is current as of December 14, 2024. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.