Introduction

Due to certain shortcomings of traditional triple and quadruple therapy for Helicobacter pylori (H. pylori), high-dose dual therapy (HDDT) is proposed as another option.

Aims & Methods

Our study aims to evaluate the efficacy and safety of HDDT, and provide more reference for clinical eradication of H. pylori. The subjects were untreated H. pylori patients from three medical centers in Central China. Totally, 439 subjects were randomly assigned to EA (esomeprazole-amoxicillin) or B-quadruple (esomeprazole-amoxicillin-clarithromycin-bismuth) group. A total of 367 subjects were randomly assigned to VA (vonoprazan-amoxicillin) or VAC (vonoprazan-amoxicillin-clarithromycin) group. The effect, adverse events, compliance, symptom relief and cost were recorded.

Results

EA-dual was non-inferior to B-quadruple regimen in mITT and PP analysis (P<0.025). But the eradication rate of EA was lower than that of B-quadruple group (70.59% vs. 83.49%, 92.86% vs. 98.38%, 93.94% vs. 98.38%, ITT, mITT, PP respectively, P<0.05). In ITT, mITT and PP analysis, VA-dual was non-inferior to VAC treatment (84.15% vs. 83.15%, 96.25% vs. 92.73%, 96.75% vs. 93.75%, P<0.025). There was no significant difference in adverse events, compliance, and symptom relief between groups. Cost of VA was the lowest. Antibiotics use within 2 years, poor compliance and suburban area residence reduced the eradication efficacy (P<0.05).

Conclusion

The HDDT based on esomeprazole or vonoprazan was non-inferior to the classical B-quadruple or VAC triple regimen. So, the HDDTs should be recommended as first-line therapies of H. pylori eradication. Antibiotics use in 2 years, adherence and residence were crucial for eradication.

Disclosure

The authors declare that they have no conflict of interest.

Introduction

It remains uncertain if the addition of Saccharomyces boulardii (S. boulardii) to Vonoprazan-amoxicillin dual therapy as a first-line treatment can enhance the Helicobacter pylori (H. pylori) eradication rate and decrease the incidence of adverse events. Therefore, we conducted the randomized controlled trials (RCTs) to address this issue.

Aims & Methods

This is a single-center, prospective randomized controlled study. A total of 150 eligible patients, recruited from December 2023 to November 2024, were randomly assigned to the VA (vonoprazan 20 mg twice daily, amoxicillin 750 mg 3 times daily for 10 days) and VAS groups (vonoprazan 20 mg twice daily, amoxicillin 750 mg 3 times daily, and S. boulardii 250 mg twice daily for 10 days). The eradication rates, adverse events, safety, and compliance were compared between the two groups. Factors associated with eradication rate were explored.

Results

The eradication rates of VA and VAS were 89.3% and 93.3%, respectively, by intention-to-treat analysis (P = 0.384); 93.1%, and 94.6%, respectively, by per-protocol analysis (P=0.966). The incidence of adverse events significantly lower in the VAS group (5.4%) than in the VA group (22.2%; P=0.003). There was no significant difference in compliance between the VA (96%) and VAS groups (98.7%, P = 0.612). Body surface area (BSA) was found to be a influencing factor for eradication rate in both VA and VAS groups. Serum chemistry tests revealed no significant differences in liver and kidney function before and after treatment in both groups.

Conclusion

Although the addition of S. boulardii to VA dual therapy could not increase the eradication rate, it could decrease the incidence of adverse events. Low-BSA patients are more suitable candidates for this regimen.

Introduction

This study investigates the dynamic mechanisms by which Helicobacter pylori (Hp) eradication therapy influences gut microbiota and metabolome. Current rescue regimens, specifically high-dose dual therapy (HDDT) combining vonoprazan (VPZ) and amoxicillin, lack thorough exploration regarding their effects on gut microbiota and host metabolism. Additionally, the timing of probiotic intervention remains poorly understood.

Aims & Methods

Utilizing multi-omics approaches, this study aims to clarify how probiotics administered at different times influence gut microbial composition, metabolic profiles, and their interaction in patients undergoing Hp rescue therapy, thereby providing a theoretical foundation for enhancing Hp eradication strategies through microbial-metabolic modulation.
From January to December 2024, 120 patients undergoing Hp rescue therapy were randomized into four groups (A–D). Group A received VPZ 20 mg bid + amoxicillin 0.75 g qid for two weeks, followed by Bacillus subtilis dual-strain enteric-coated capsules (2 tablets tid) for two weeks. Group B received VPZ 20 mg bid + amoxicillin 0.75 g qid + Bacillus subtilis capsules (2 tablets tid) for two weeks. Group C was treated with VPZ 20 mg bid + amoxicillin 0.75 g tid for two weeks. Group D received Bacillus subtilis capsules (2 tablets tid) for two weeks, followed by VPZ 20 mg bid + amoxicillin 0.75 g qid for two weeks. Twenty-five Hp-negative individuals served as controls. Fecal samples were collected at baseline, 4 weeks, and 12 weeks post-treatment. Gut microbiota diversity and composition were analyzed through metagenomic sequencing; untargeted metabolomics was conducted using LC-MS; and small intestinal bacterial overgrowth was assessed via hydrogen-methane breath testing.

Results

1) No significant differences in gut microbiota alpha (Shannon index) or beta diversity (Bray-Curtis) were observed between H. pylori (Hp)-infected and uninfected groups (P=0.65). Hp-positive individuals exhibited elevated Collinsella aerofaciens and reduced Roseburia faecis and Agathobacter spp. (P<0.05). Metabolomic analysis identified 886 differentially abundant metabolites (P<0.05, VIP>1, FC≠1) enriched in 45 KEGG pathways, with key biomarkers including deoxyribose 5-phosphate and 4-vinylcyclohexene dioxide (P<0.01). The prevalence of SIBO was higher in patients with H. pylori infection than in those without infection (P<0.05). 2) Post-treatment alpha/beta diversity remained stable across groups A–D (P>0.05). Metabolic pathway profiles diverged: Group A emphasized phenylpropanoid biosynthesis; Group B showed cytochrome P450 drug metabolism; Group C featured sphingolipid metabolism and necroptosis; Group D upregulated cofactor/flavonoid biosynthesis. No significant SIBO changes occurred post-treatment in any group. 3) At week 4, beta diversity separation (P=0.009) was driven by Bacillota, Blautia, Ruminococcus sp., and Phocaeicola sp., with metabolites like Fahfa(3:0/24:1) linked to inflammation. By week 12, Groups B and C displayed distinct alpha (Sobs) and beta diversity (P=0.011), distinguished by Escherichia coli and Faecalibacterium prausnitzii. Group C exhibited upregulated anti-inflammatory metabolites (e.g., luteolin) and mucosal repair markers. 4) Multi-omics integration revealed early metabolic compensation at week 4 (Bifidobacterium-mediated amino acid/bile acid homeostasis) and late-stage recovery (week 12) marked by Pseudomonadota proliferation (E. coli) and Faecalibacterium grausatizii-associated sulfated steroids/phosphosphingolipids, supporting immune regulation and mucosal repair.

Conclusion

Probiotic-augmented HDDT has minimal impact on gut microbiota diversity and small intestinal bacterial overgrowth but significantly enhances the probiotic-microbiota-metabolite axis, particularly in sustaining anti-inflammatory metabolites and immune regulation.

Disclosure

The authors have no conflicts of interest to declare.

Introduction

The increasing prevalence of antibiotic resistance and the scarcity of therapeutic options for patients with penicillin allergy have highlighted the necessity for novel treatment regimens. Keverprazan, a novel potassium-competitive acid blocker, provides potent and sustained gastric acid suppression.

Aims & Methods

This study was designed to evaluate the efficacy and safety of keverprazan-minocycline (KM) dual therapy compared with keverprazan-amoxicillin (KA) dual therapy in patients with Helicobacter pylori (H. pylori) infection. From October 2024 to April 2025, a total of 240 patients with H. pylori infection were recruited from six hospitals in Fujian province and randomly assigned to receive either KA dual therapy (amoxicillin 1 g three times daily plus keverprazan 20 mg once daily) or KM dual therapy (minocycline 100 mg twice daily plus keverprazan 20 mg once daily) for a duration of 14 days. The primary endpoint was the H. pylori eradication rate assessed at 4 weeks post-treatment. Secondary endpoints included the symptom relief rate, incidence of adverse events, and patient compliance.

Results

In the intention-to-treat (ITT) analysis, the H. pylori eradication rates were 85.83% (103/120) in the KA group and 87.50% (105/120) in the KM group. In the per-protocol (PP) analysis, the eradication rates were 86.95% (100/115) in the KA group and 90.35% (102/113) in the KM group. No statistically significant differences were observed between the two groups (P = 0.704 for ITT and P = 0.421 for PP analysis). Additionally, symptom remission rates (73.88% vs. 82.50%) and treatment adherence rates (97.01% vs. 97.50%) also showed no significant intergroup differences (both P > 0.05). However, the KM group exhibited a significantly higher overall incidence of adverse events compared with the KA group (38.33% vs. 17.16%, P < 0.001), primarily driven by mild dizziness (25.83% vs. 2.23%, P < 0.001). However, these adverse reactions were mild and did not affect treatment adherence.

Conclusion

The keverprazan-minocycline dual regimen demonstrated high eradication efficacy and acceptable safety in patients with H. pylori infection, with eradication effectiveness comparable to that of the keverprazan-amoxicillin dual therapy and mild adverse reactions. This regimen is recommended for the clinical treatment of H. pylori infection, particularly in patients with penicillin allergy.

Disclosure

There is no conflict of interest.

Introduction

Helicobacter pylori (Hp) infection remains a major public health problem, associated with significant morbidity and mortality, whose eradication therapy has proven to be effective in preventing these complications.^1,2 Given the high resistance to antibiotics and the scarcity of available antibiotic therapy worldwide, there is not enough data on the best eradication strategy.^3,4

Aims & Methods

Aim: The aim of this study was to perform a comparative evaluation of the efficacy and safety of the different quadruple therapy regimens currently recommended for the Hp eradication, including Esomeprazole 40 mg bid.
Methods: A blind randomized controlled clinical trial of consecutive patients with gastric infection by Hp, diagnosed by 13C-urea breath test (UBT) or histological analysis were randomized in 5 therapy arms (A: Quadruple with metronidazole 500 mg tid, 14 days; B: Quadruple with metronidazole 500 mg bid, 14 days; C: Quadruple with bismuth, 10 days; D: Sequential, 7 days; E: Hybrid, 7 days). Hp eradication with evaluation of the efficacy and safety rates at 1-2 months after the eradication therapy was made.

Results

From a total of 200 patients currently included, 193 concluded the protocol study (164-histological analysis; 29-UBT), 102 males (52.8%), mean age of 57.2±16.3 (A: 38; B: 39; C: 38; D: 41; E: 37). Overall efficacy rate of quadruple therapy regimens was 95.9% (n=185), being 100.0% for arm A, 92.3% for arm B, 97.3% for arm C, 97.6% for arm D and 91.9% for arm E (p=0.431). Overall adverse events rate of quadruple therapy regimens was 53.9% (n=104), being diarrhea (27.5%) and nausea (26.9%) the most common. Major symptoms (need for therapy or impairment of daily living activities) occurred in 8.3%. Adverse events/Major adverse events rates for the different regimens were 50.0%/5.3% for arm A, 69.2%/15.4% for arm B, 48.6%/7.9% for arm C, 48.8%/4.9% for arm D and 54.0%/8.1% for arm E (p=0.287/p=0.451).

Conclusion

In Portugal, all the quadruple therapy regimens currently recommended for the eradication of Hp, with or without bismuth, have been effective in eradicating Hp gastric infection. However, concomitant therapy with metronidazole bid seems to have a higher rate of adverse effects, including major adverse effects.

References

1. Zamani, M., Ebrahimtabar, F., Zamani, V., et al. Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther 2018; 47(7): 868-876.
2. Malfertheiner, P., Megraud, F., O’Morain, C.A., et al. Management of Helicobacter pylori infection – the Maastricht V/Florence Consensus Report. Gut 2017; 66(1): 6-30.
3. Savoldi, A., Carrara, E., Graham, D.Y., et al. Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in World Health Organization Regions. Gastroenterology 2018; 155(5): 1372-1382.
4. Lopo, I., Libânio, D., Pita, I., et al. Helicobacter pylori antibiotic resistance in Portugal: Systematic review and meta[1]analysis. Helicobacter 2018; 23(4): e12493.

Disclosure

Nothing to declare.

Introduction

Due to the increasing prevalence of antimicrobial resistance, the efficacy of standard triple therapy for Helicobacter pylori (H. pylori) infection has declined, with eradication rates now falling below 80% in most countries. Although bismuth quadruple therapy and concomitant therapy are advised in regions with high clarithromycin resistance, these treatments commonly cause frequent adverse events and require the use of two or three antibiotics.

Aims & Methods

Aim: To evaluates the effectiveness of 14-day mono-antibiotic therapies for the first-line treatment of H. pylori infection.
Methods: Randomized controlled trials published in English that reported the efficacies of 14-day high-dose amoxicillin/PPI dual, 14-day high-dose amoxicillin/vonoprazan dual, and 14-day tetracycline/vonoprazan dual therapies for the first-line treatment of H. pylori infection in adults were included in our literature search. Medical literature searches were conducted using PubMed, Embase, and Cochrane Library electronic databases from October 1, 2014, to October 1, 2024.

Results

The pooled eradication rates for 14-day high-dose amoxicillin/proton-pump inhibitor (PPI) dual therapies were 86.1% (3335/3875; 95% confidence interval [CI]: 85.1% - 87.2%) by intention-to-treat (ITT) analysis and 87.3% (3232/3702; 95% CI: 86.2% - 88.4%) by per-protocol (PP) analysis. For 14-day high-dose amoxicillin/vonoprazan dual therapies, the rates were 87.4% (1085/1241; 95% CI: 85.5% - 89.2%) by ITT and 93.0% (1044/1124; 95% CI: 91.5% - 94.5%) by PP. In the penicillin-allergic population, 14-day tetracycline/vonoprazan dual therapy showed eradication rates of 92.0% (138/150) by ITT and 95.1% (135/142) by PP.

Conclusion

14-day tetracycline/vonoprazan dual therapy presents an effective option for eradicating H. pylori in patients allergic to penicillin. For those without a penicillin allergy, first-line treatments can include 14-day mono-antibiotic regimens such as high-dose amoxicillin/PPI dual, high-dose amoxicillin/vonoprazan dual, and tetracycline/vonoprazan dual therapies.

Disclosure

All the authors disclose no conflict of interest.