Introduction

Helicobacter pylori (H. pylori) remains a significant global pathogen, implicated in chronic gastritis, peptic ulcer disease, and gastric cancer. Over the past two decades, escalating resistance to key antibiotics—particularly clarithromycin, levofloxacin, and metronidazole—has reduced the effectiveness of standard triple therapies, with eradication rates falling below 70%. Refractory H. pylori infection, defined in this study as persistent infection after three or more failed eradication regimens, presents a growing therapeutic challenge. The absence of standardised rescue protocols and limited access to antibiotic susceptibility testing in many regions further complicates treatment. Innovative empirical strategies, especially those using agents with low resistance profiles, are urgently needed.

Aims & Methods

This real-world, prospective observational study aimed to evaluate the efficacy of a Modified Concomitant Therapy (MCT) regimen for the eradication of refractory H. pylori. Adults aged ≥18 years with confirmed H. pylori infection persisting after at least three previous treatment attempts were recruited from a gastroenterology centre in Bogotá, Colombia, between January and November 2023.

The MCT protocol included:

• Esomeprazole 40 mg, twice daily (before breakfast and dinner)
• Furazolidone 100 mg, every 8 hours
• Amoxicillin 875 mg every 8 hours (in patients <70 kg) or 1 g every 8 hours (in ≥70 kg)
• Tetracycline 500 mg, every 6 hours

Patients were counselled about the therapeutic difficulty and potential adverse effects. The treatment duration was 14 days. Eradication was assessed 6–8 weeks post-therapy using histological evaluation with haematoxylin-eosin and Giemsa staining. This choice was based on prior discordance between breath test results (often negative) and biopsy (positive). Effectiveness was analysed both by modified intention-to-treat (mITT) and per-protocol (PP) methods.

Results

A total of 30 patients were enrolled (mean age: 45 ± 6 years; range: 28–63).

• mITT eradication rate: 27/30 (90%, 95% CI: 72.3–97.4)
• PP eradication rate: 25/27 (92.5%, 95% CI: 76.3–97.9)

Adverse events were reported in 8 patients:

• Nausea (30%)
• Headache (33%)
• Diarrhoea (16%)
• Constipation (10%)

Three patients discontinued treatment prematurely between days 10 and 12. No severe adverse events or hospitalisations occurred. The major limiting factor for broader enrolment was intermittent availability of tetracycline.

Conclusion

This study demonstrates that Modified Concomitant Therapy represents a promising and effective option for the eradication of refractory H. pylori infection in real-world settings. With an eradication rate exceeding 90% and manageable adverse effects, MCT using furazolidone, amoxicillin, tetracycline, and high-dose PPI constitutes a rational empirical rescue strategy in regions where antibiotic resistance testing is unavailable and first-line therapies have failed. Further multicentre studies with larger cohorts are warranted to confirm these findings and assess long-term outcomes. The development of accessible tetracycline formulations would enhance implementation.

References

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