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

1. Malfertheiner P, Megraud F, Rokkas T, Gisbert JP, Liou JM, Schulz C, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022 Jan;71(1):172–95. doi:10.1136/gutjnl-2021-325210.
2. Graham DY, Lee YC, Wu MS. Rational Helicobacter pylori therapy: evidence-based medicine rather than medicine-based evidence. Clin Gastroenterol Hepatol. 2014 Feb;12(2):177–86.e3. doi:10.1016/j.cgh.2013.06.020.
3. Liou JM, Chen CC, Chang CY, Chen MJ, Fang YJ, Lee JY, et al. Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet. 2013 Feb 16;381(9862):205–13. doi:10.1016/S0140-6736(12)61455-0.

Introduction

The global prevalence of Helicobacter pylori (HP) infection is almost 43% and affects almost 18% of Italians [1, 2]. The literature describes several endoscopic signs detectable during upper-GI endoscopy that may predict HP status [3]; however, in clinical practice, random biopsies according to the Sydney system are still widely used for its determination.

Aims & Methods

The aim of our study is to investigate the role of Regular arrangement of collecting venules (RAC) assessment, during upper-GI endoscopies, for predicting HP status. We conducted a monocentric prospective study including patients who underwent upper-GI endoscopy for any indications from August 2024 to February 2025. Upper-GI endoscopies were performed according to standard of care [4], with high-definition scopes and after adequate cleaning [5]. Exclusion criteria were autoimmune gastritis, antibiotics within the previous 4 weeks, gastric surgery, previous endoscopic submucosal resection, upper-GI neoplasms, age <18 years, severe liver/kidney disease and previous known HP infection. Every procedure was performed by 6 endoscopists trained in recognition of all typical endoscopic signs of healthy stomach or HP infection: RAC, fundic gland polyps, linear streaks, hematin spots and diffuse redness prior to data collection. HP infection was investigated by histological evaluation by bioptic sampling, obtained according to the Sydney criteria.

Results

From 429 enrolled patients, 244 patients were included, according to inclusion criteria (M 124, 50.8%, median age 54.9, IQR 41.9-65.0). The prevalence of H. pylori infection was 15.5% (38/244). The presence of RAC in both greater and lesser curvature was observed in 63.1% (154/244) of cases, gland polyps in 19.6% (48/244), linear streaks in 15.5% (38/244), hematin spots in 15.9% (39/244) and diffuse redness in 9% (22/244). The presence of RAC, gland polyps and diffuse redness were significantly associated with higher prevalence of HP infection (p<0.001). The best performance was obtained from the presence of RAC in both greater and lesser curvature (AUROC 0.808, p<0.001) with a sensitivity (SEN), specificity (SPE), NPV and PPV respectively of 82.7% (64.2-94.1), 78.8% (72.3-84.4), 96,2% (92-98.3) and 40.8% (33.3-48.7). At multivariate analysis it confirmed to be related to HP-negative status (p=0.01, OR 0.04 95%CI: 0.005-0.481). Lastly, the presence of RAC showed a higher performance in males (AUROC 0.836, SEN 86.6% 59.5-98.3, SPE 80.6% 71.4-87.9, NPV 97.1% 90.3-99.2, PPV 44.1% 33.4-55.3) and in young patients (AUROC 0.846, SEN 80% 51.9-95.6, SPE 89.2% 81.1-94.7, NPV 96.2% 90.1-98.6, PPV 56.7% 40.9-71.3). As expected, the presence of RAC required a very short observation time (29.3 ± 11.0 versus 34.7 ± 11.7 seconds; p=0,001).

Conclusion

The presence of RAC in both the greater and lesser curvatures is the most important and reliable indicator of HP-negative status, and the time required for the evaluation is minimal. Our findings may represent a first step toward avoiding unnecessary random biopsies, promoting a more accurate endoscopic examination focused on the careful assessment of the gastric mucosa

References

1. Chen YC, et al. Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022. Gastroenterology, 2024
2. Zullo A, et al. Upper Endoscopy in Patients with Extra-Oesophageal Reflux Symptoms: A Multicentre Study. GE Port J Gastroenterol, 2020
3. Seo JY, et al. Predicting Helicobacter pylori infection from endoscopic features. Korean J Intern Med, 2024
4. Bisschops R, et al. Performance measures for upper gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative. Endoscopy, 2016
5. Manfredi G, et al. Premedication with simethicone and N-acetylcysteine for improving mucosal visibility during upper gastrointestinal endoscopy in a Western population. Endosc Int Open, 2021