What are the treatment options for Helicobacter pylori (H. pylori) infection after failure of initial treatment?

From the Guidelines

After failure of initial Helicobacter pylori treatment, a 10-day levofloxacin-amoxicillin triple therapy is recommended as second-line therapy. This recommendation is based on a strong recommendation with moderate-quality evidence 1. The suggested doses for this regimen are a proton pump inhibitor (PPI) standard dose twice a day, levofloxacin 500 mg once a day or 250 mg twice a day, and amoxicillin 1000 mg twice a day 1.

The choice of second-line therapy should ideally be guided by antimicrobial susceptibility testing when available, as H. pylori resistance patterns vary geographically 1. However, individual susceptibility testing is generally only advised after second-line treatment failure due to cost and logistics 1.

Some key points to consider when treating H. pylori after initial treatment failure include:

• Confirming eradication with either a urea breath test, stool antigen test, or endoscopic biopsy at least 4 weeks after completing therapy and while off proton pump inhibitors for at least 2 weeks 1.
• Using different antibiotics in the second-line regimen to overcome resistance, particularly to clarithromycin and metronidazole 1.
• Counseling patients about potential side effects and the importance of completing therapy to ensure successful eradication 1.
• Considering bismuth quadruple therapy as an alternative salvage therapy if levofloxacin is not suitable 1.

It's essential to note that treatment failure often occurs due to antibiotic resistance, and patient adherence to the full course of treatment is crucial for successful eradication 1.

From the FDA Drug Label

Adult Patients only Helicobacter pylori Infection and Duodenal Ulcer Disease: Triple therapy for Helicobacter pylori (H. pylori) with clarithromycin and lansoprazole : Amoxicillin, in combination with clarithromycin plus lansoprazole as triple therapy, is indicated for the treatment of patients with H pylori infection and duodenal ulcer disease (active or 1-year history of a duodenal ulcer) to eradicate H. pylori. Dual therapy for H. pylori with lansoprazole : Amoxicillin, in combination with lansoprazole delayed-release capsules as dual therapy, is indicated for the treatment of patients with H pylori infection and duodenal ulcer disease (active or 1-year history of a duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected.

The FDA drug label does not provide information on the treatment of H. pylori after failure of treatment. 2

From the Research

Treatment of H. pylori after Failure of Treatment

• The treatment of H. pylori after failure of initial treatment is a significant concern, with various studies exploring different therapeutic regimens 3, 4, 5, 6, 7.
• A study published in 2016 found that a 14-day regimen of levofloxacin, bismuth, amoxicillin, and esomeprazole (LBAE) achieved eradication rates of 73.5% and 78.5% in intention-to-treat and per-protocol analyses, respectively 3.
• Another study published in 2024 reviewed newer therapies for refractory H. pylori infection, including high-dose PPI-amoxicillin dual therapy, vonoprazan-based therapy, and rifabutin-containing triple therapy, which demonstrated high eradication rates and acceptable safety profiles 4.
• A 2009 study found that a 7-day PPI-triple therapy with levofloxacin was very effective for H. pylori eradication, with overall cure rates of 96% and 93% in two treatment groups 5.
• The role of antibiotic resistance in treatment failure is a significant concern, with studies highlighting the need for alternative therapeutic regimens in cases of resistance 3, 6.
• Modified sequential H. pylori therapy, such as a 14-day hybrid therapy with a proton pump inhibitor and amoxicillin, followed by a quadruple therapy for the final 7 days, has also been shown to achieve high eradication rates 7.

Therapeutic Regimens

• Levofloxacin, bismuth, amoxicillin, and esomeprazole (LBAE) regimen: 73.5% and 78.5% eradication rates in intention-to-treat and per-protocol analyses, respectively 3.
• High-dose PPI-amoxicillin dual therapy: 81.3% to 89.2% eradication rates 4.
• Vonoprazan-based therapy: 83.3% to 89.5% eradication rates 4.
• Rifabutin-containing triple therapy: 80.7% to 100% eradication rates 4.
• 7-day PPI-triple therapy with levofloxacin: 96% and 93% overall cure rates in two treatment groups 5.
• Modified sequential H. pylori therapy: 99.1% and 97.4% eradication rates in per-protocol and intention-to-treat analyses, respectively 7.

Factors Influencing Treatment Outcome

• Antibiotic resistance: a significant factor in treatment failure, with levofloxacin resistance and history of quinolone intake identified as independent predictors of treatment failure 3.
• Patient compliance: high compliance rates (94.9% to 96.1%) reported in several studies 3, 7.
• Adverse events: varying frequencies of adverse events reported in different studies, with some regimens associated with higher rates of adverse events 3, 4, 5, 7.