The identification of Helicobacter pylori (H. pylori) infection as the primary etiology of gastroduodenal diseases represents a significant advancement in the field of gastroenterology. The management of these diseases has undergone a substantial transformation, and antibiotic treatment is now universally applicable. H. pylori has been the subject of numerous investigations to determine the prevalence of antibiotic resistance. However, many of these studies are limited, particularly regarding the number and representativeness of the strains assessed. Genetic and physiological modifications, such as gene mutations, efflux pump alterations, biofilm formation, and coccoid formation, contribute to the observed resistance. Our review focuses on the emergence of antibiotic-resistant strains, particularly emphasizing the various modifications of H. pylori that confer this resistance. In conclusion, we elucidate the challenges, potential solutions, and prospects in this field, providing researchers with the knowledge necessary to overcome the resistance exhibited by H. pylori.

To assess the risk factors associated with Helicobacter pylori infection in the urban Chinese population.

The study was conducted from March to November 2023, including 12,902 urban participants aged 18-60 years across 52 cities distributed over 26 provinces in China. Risk factors included socioeconomic status, lifestyles, and public understanding. Univariate and multivariate logistic regression analysis was used to calculate corrected odds ratios (ORs) and 95% confidence intervals (CIs).

According to multivariate logistic regression, risk factors associated with significantly higher H. pylori infection rates included residency in developing (OR 1.27, 95% CI 1.13-1.43) and undeveloped cities (OR 1.15, 95% CI 1.02-1.29), obesity (OR 1.37, 95% CI 1.05-1.78), alcohol consumption (OR 1.16, 95% CI 1.05-1.29), tea consumption (OR 1.11, 95% CI 1.01-1.21), and soft drink consumption (OR 1.24, 95% CI 1.09-1.40). Conversely, individuals with moderate awareness (OR 0.79, 95% CI 0.71-0.88) and high awareness (OR 0.57, 95% CI 0.48-0.69) of H. pylori had lower infection rates.

Our findings highlight the importance of promoting a healthy lifestyle and improving the understanding of H. pylori in reducing the infection rate of the bacterial pathogen in the urban Chinese population.

The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections.

This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups.

A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% in Group A, 89.6% in Group B, 89.1% in Group C, and 87.7% in Group D. The per-protocol (PP) eradication rates were 92.9% in Group A, 94.5% in Group B, 94.5% in Group C, and 93.6% in Group D. There was no statistical difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups.

The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs.

ClinicalTrials.gov , NCT05173493.

Helicobacter pylori is associated with gastrointestinal diseases including gastritis and peptic ulcers. Despite its significance, there is a scarcity of antimicrobial susceptibility testing (AST) data available for this organism in North America.

The aim of this study was to assess the AST profile and identify factors associated with H. pylori culture positivity in a cohort of patients with refractory H. pylori undergoing gastric biopsies.

We retrospectively reviewed gastric biopsy specimens received for culture between July 2009 and February 2023. We analyzed specimen transport time, Gram smear results, direct urease test findings, culture positivity and AST profiles. Using gradient strip methodology and European Committee on Antimicrobial Susceptibility Testing breakpoints, AST was conducted for amoxicillin, clarithromycin, metronidazole, levofloxacin and tetracycline.

Of 579 biopsy samples received for H. pylori culture, 228 (39.4%) tested positive. Samples transported within <1 h had significantly higher odds (1.81 times, P < 0.015) of being culture positive compared to those with longer transport times. Smear-positive samples had substantially higher odds (18.8 times, P < 0.001) of culture positivity compared to smear-negative. Urease-positive samples demonstrated notably higher odds (7.7 times, P < 0.001) of culture positivity compared to urease-negative samples. The collection of isolates from gastric biopsies showed susceptibility rates of 97.3% to amoxicillin, 99.1% to tetracycline, 50.4% to levofloxacin, 25.9% to metronidazole and 12.9% to clarithromycin.

Short sample transport time was associated with improved H. pylori recovery rates. In this cohort of refractory H. pylori cases, susceptibility rates were high for amoxicillin and tetracycline and low for clarithromycin, metronidazole and levofloxacin. Susceptibility rates remained stable over time.

In the last few years, numerous new potassium-competitive acid blocker (P-CAB)-based randomized controlled trials (RCTs) concerning the first-line regimens for Helicobacter pylori infection treatment from various countries have been published. However, no network meta-analysis (NWM) exists, which examines the comparative efficacy and safety of P-CAB-based dual, triple, and quadruple treatments, and, therefore, in this NWM, we examined this matter comparing efficacy and safety of these P-CAB-based regimens.

Databases were searched for identification, screening, eligibility, and inclusion of relevant RCTs. Extracted data were entered into a Bayesian NWM, and the ranking order for each regimen was evaluated by means of the surface under the cumulative ranking area values.

Twenty-five eligible RCTs were included with 7,605 patients randomized to 6 first-line regimens, i.e. P-CAB dual therapy, P-CAB triple therapy, P-CAB quadruple therapy, PPI dual therapy, PPI triple therapy, and PPI quadruple therapy. The surface under the cumulative ranking area values (%) for these 6 regimens were 92.7, 62.5, 33.9, 75.1, 19.4, and 16.3, respectively. The comparative effectiveness ranking showed that P-CAB dual therapy regimen ranked first for efficacy and last for adverse effects and had the best profile for integrated efficacy-safety.

In this NWM concerning the comparative efficacy and safety of P-CAB-based dual, triple, and quadruple regimens for the first-line H. pylori infection treatment, the overall results showed that P-CAB-based dual treatment ranked first for efficacy with the best-integrated efficacy-safety profile. This is of importance, since the dual regimens overcome the crucial issue of clarithromycin resistance. Consequently, these findings are expected to be useful in helping clinical decision making and future guidelines.

Exploring host cell specificity, pathogenicity, and molecular mechanisms of the vacuolating cytotoxin A (VacA), secreted by Helicobacter pylori (Hp) is crucial for developing novel treatment strategies. VacA affects subcellular events, particularly mitochondria, at a cell-type-specific level. However, the lack of reliable models that mimic VacA-induced subcellular damages and enable novel drug screening linked to the human stomach clinically limits our understanding of the mitochondrial networks in vivo. Here, human antrum gastric organoids (hAGOs) and tissue samples from Hp-infected patients were used to show the toxic effects of VacA-induced mitochondrial damage mainly in mucus-producing gastric pit cells by employing transcriptional, translational, and functional analyses. In VacA-intoxicated or Hp-infected hAGOs, robust mitochondrial fragmentation in gastric pit cells reduced ATP production during respiration, and loss of mucosal barrier integrity was first demonstrated experimentally. Using hAGOs, clinically relevant small molecules were screened for efficacy, and MLN8054, an Aurora kinase A inhibitor, reversed VacA-induced mitochondrial damage and loss of gastric epithelium integrity. MLN8054 was effective in VacA-treated and Hp-infected hAGOs and mice, highlighting hAGOs as a promising drug-screening model. These findings suggest that mitochondrial quality control may serve as a promising therapeutic target for Hp VacA-mediated toxicity and disease progression.

Concerns have been raised regarding the decreasing success rates of the standard treatment of Helicobacter pylori (proton pump inhibitor (PPI) and two/three antibiotics) and the long-term effects carried by PPI. Despite conflicting data, Tegoprazan, a potassium-competitive acid blocker, is hypothesized to be superior to PPI for eradicating H pylori. This systematic review and meta-analysis aim to determine the superiority of Tegoprazan-containing therapy to PPI-containing therapy for H pylori eradication.

A systematic literature search identified studies published until December 12, 2024, from MEDLINE, EMBASE, SCOPUS, and CENTRAL. The search strategy included the following keywords: "Tegoprazan," "Proton Pump Inhibitors," and "Helicobacter pylori." Only randomized controlled trials (RCTs) that compared the efficacy of Tegoprazan to any PPI were included. Risk of bias assessment was performed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs. The random-effect model was used to calculate the pooled risk ratio (RR) and its 95% Confidence Interval (95% CI) from the intention-to-treat population.

Six RCTs with low risks of bias were included in this meta-analysis. All studies included treatment-naïve patients and compared first-line H pylori treatment. The overall eradication rates of Tegoprazan-containing (N = 1052) versus PPI-containing therapy (N = 1058) were 83.37% and 80.06%, respectively (RR 1.045; 95% CI 1.008-1.084; I 2 = 0%). Tegoprazan-containing therapy demonstrated comparable treatment-emergent adverse event (TEAE) rates compared to PPI-containing therapy (46.48% vs. 46.31%; RR 1.026; 95% CI 0.952-1.106; I 2 = 48%).

This meta-analysis demonstrated that Tegoprazan-containing therapy is superior to PPI-containing therapy for first-line H pylori eradication, with comparable safety profiles.

Owing to the high prevalence of antibiotic resistance in Helicobacter pylori (H. pylori) in China, bismuth-containing quadruple therapies have been recommended for H. pylori eradication. This study compared the efficacy and safety of quadruple regimens containing vonoprazan vs. esomeprazole for H. pylori eradication in a patient population in China.

This was a phase 3, multicenter, randomized, double-blind study. Patients with confirmed H. pylori infection were randomized 1:1 to receive quadruple therapy for 14 days: amoxicillin 1000 mg and clarithromycin 500 mg after meals, bismuth potassium citrate 600 mg before meals, plus either vonoprazan 20 mg or esomeprazole 20 mg before meals, all twice daily. The primary outcome was the eradication rate of H. pylori, evaluated using a 13C urea breath test at 4 weeks after treatment. The non-inferiority margin was at 10%.

The study included 510 patients, 506 of whom completed the follow-up assessment. The primary analysis revealed eradication rates of 86.8% (210/242) and 86.7% (208/240) for vonoprazan and esomeprazole therapy, respectively (treatment difference: 0.1%; 95% confidence interval [CI]: -5.95, 6.17; non-inferiority P = 0.0009). Per-protocol analysis showed eradication rates of 87.4% for vonoprazan and 86.3% for esomeprazole (treatment difference: 1.2%; 95% CI: -5.03, 7.36; non-inferiority P = 0.0004). Vonoprazan and esomeprazole were well tolerated, with similar safety profiles.

Vonoprazan was found to be well-tolerated and non-inferior to esomeprazole for eradicating H. pylori in patients from China.

ClinicalTrials.gov, NCT04198363.

The increasing prevalence of clarithromycin (CLA)-resistant Helicobacter pylori(H. pylori) strains poses a significant challenge in the management of H. pylori infections. This systematic review and meta-analysis investigates the diagnostic accuracy of polymerase chain reaction (PCR) in identifying CLA-resistant H. pylori strains in stool.

A comprehensive literature search was conducted using PubMed, Embase, and Cochrane databases from database inception to April 30, 2023. Eligible studies evaluated the effectiveness of PCR stool tests in detecting CLA-resistant H. pylori strains in adults (>18-year-old). Studies of pediatric populations, alternative methods to PCR or stool samples, and reference tests other than gastric biopsy were excluded. The bivariate random-effects model was used to pool diagnostic accuracy from the included studies.

The analysis of 11 prospective diagnostic studies with a total of 866 patients showed a pooled sensitivity of 0.97 (95% CI: 0.9-0.99) and a pooled specificity of 0.98 (95% CI: 0.81-1.00). Subgroup analysis based on the used technique demonstrated consistent findings without notable variations. The diagnostic odds ratio was calculated at 1843.92 (95% CI: 134.28-25,321.3). The positive likelihood ratio was determined as 51.02 (95% CI: 4.61-564.5), while the negative likelihood ratio was found to be 0.03 (95% CI: 0.01-0.1).

PCR testing for clarithromycin-resistant H. pylori was highly sensitive and specific across studies with proven reliability in clinical practice, particularly in outpatient settings. Their implementation offers cost-effectiveness and the potential for tailored treatment strategies, holding promise for improved patient outcomes.

Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori.

A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14 days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4 weeks after treatment completion.

Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P < 0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P < 0.001).

Triple therapy comprising vonoprazan (20 mg), amoxicillin (750 mg), and bismuth potassium citrate (220 mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients.

Helicobacter pylori (H. pylori) is the most common chronic bacterial infection in humans. The risk of acquiring H. pylori is related to socioeconomic status and living conditions early in life. Treatment regimens must consider local antibiotic resistance patterns. Adventist Health White Memorial Hospital serves a predominantly indigent population in east Los Angeles with a large number of immigrants from South and Central America. Data regarding the prevalence and resistance of H. pylori in this population is scant.

To evaluate the prevalence and resistance of H. pylori and correlate with country of origin.

All gastric biopsies were obtained by a single gastroenterologist at the hospital in a consecutive manner from patients with gastritis from 2017 to 2022 and sent to various labs for evaluation.

Two hundred and sixty-six patients are born in the United States, 450, 171, 70, and 30 patients are immigrants from Mexico, Central and South America (CSA), Asia, and other countries respectively. Overall, 14.65% were found to be infected with H. pylori. Rates of infection in United States-born citizens, immigrants from Mexico, CSA, and Asia are 9.02%, 18.67%, 13.45%, and 11.43% respectively, with Mexican immigrants having a relative risk of 2.3889 [95% confidence interval (CI): 1.4789-3.8588, P = 0.0004] compared to those born in United States. No correlation seen between infection and length of time immigrants were in United States. Relative risk of infection in patients with no proton pump inhibitor use within the past 30 days found to be 1.9276 (95%CI: 1.3562-2.7398, P = 0.0003). Rates of resistance for clarithromycin and levofloxacin are 21.43% and 31.11%.

H. pylori infection appears to be associated with low socioeconomic status and poor living conditions early in life. Clarithromycin and levofloxacin based treatment regimens should be avoided as first line therapy in this region, particularly in patients of Latin American origin.

Helicobacter pylori infection is often acquired in early childhood. While most infected children remain asymptomatic, H. pylori can cause chronic gastritis, gastric ulceration, and, in the long term, gastric cancer. This article aimed to review different diagnostic and treatment options and discuss the challenges associated with applying the current guidelines in the real world. Relevant articles published from 2015 to August 2023 in the English language in PubMed and Medline electronic databases were extracted using subject headings and keywords of interest to the topic. References of interest in the selected articles were also considered. Invasive and noninvasive diagnostic tests have advantages but also disadvantages and limitations according to the clinical setting and age of the child. Guidelines recommend not performing diagnostic testing in children with long-lasting or recurrent abdominal complaints or cases of a family history of severe disease caused by H. pylori. However, parents regularly consult with the explicit demand to test for H. pylori because of them or a close family member experiencing severe gastric disease caused by H. pylori. In some situations, it may be challenging for the healthcare professional to stick to evidence-based guidelines and not consider "patient-centered care," with the risk of putting a trustful relationship in danger. Physicians may find it challenging not to perform diagnostic tests for H. pylori and prescribe eradication treatment in specific clinical settings when maintaining a trusting patient-physician relationship by applying this "patient-centered care" method when evidence-based guidelines recommend differently.

With the increasing resistance to antimicrobial agents, susceptibility-guided tailored therapy has been emerging as an ideal strategy for Helicobacter pylori treatment. However, susceptibility-guided tailored therapy requires additional cost, time consumption, and invasive procedure (endoscopy) and its superiority over empirical quadruple therapy as the first-line H. pylori treatment remains unclear.

To compare the efficacy of culture-based susceptibility-guided tailored versus empirical concomitant therapy as the first-line Helicobacter pylori treatment.

This open-label, randomized trial was performed in four Korean institutions. A total of 312 Patients with H. pylori-positive culture test and naïve to treatment were randomly assigned in a 3:1 ratio to either culture-based susceptibility-guided tailored therapy (clarithromycin-based or metronidazole-based triple therapy for susceptible strains or bismuth quadruple therapy for dual-resistant strains, n = 234) or empirical concomitant therapy (n = 78) for 10 days. Eradication success was evaluated by 13C-urea breath test at least 4 weeks after treatment.

Prevalence of dual resistance to both clarithromycin and metronidazole was 8%. H. pylori eradication rates for tailored and concomitant groups were 84.2% and 83.3% by intention-to-treat analysis (p = 0.859), respectively, and 92.9% and 91.5% by per-protocol analysis, respectively (p = 0.702), which were comparable between the two groups. However, eradication rates for dual-resistant strains were significantly higher in the tailored group than in the concomitant group. All adverse events were grade 1 or 2 based on the Common Terminology Criteria for Adverse Events and the incidence was significantly lower in the tailored group. The proportion of patients discontinuing treatment for adverse events was comparable between the two groups (2.1% vs. 2.6%).

The culture-based susceptibility-guided tailored therapy failed to show superiority over the empirical concomitant therapy in terms of eradication rate. Based on these findings, the treatment choice in clinical practice would depend on the background rate of antimicrobial resistance, availability of resources and costs associated with culture and susceptibility testing.

The decreasing Helicobacter pylori eradication rate is primarily attributed to antibiotic resistance, and further exacerbated by uniform drug administration disregarding a host's metabolic capability. Consequently, applying personalized treatment based on antibiotic resistance-associated variants and the host's metabolic phenotype can potentially increase the eradication rate.

A custom next-generation sequencing panel for personalized H. pylori eradication treatment (NGS-PHET) was designed which targeted the regions for amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin-resistance in H. pylori and human proton-pump inhibitor (PPI) metabolism. The libraries were constructed following customized methods and sequenced simultaneously. The customized framework criteria, grounded in previously reported antibiotic resistance associated variants and the host's PPI metabolism, was applied to the NGS-PHET results and suggested a personalized treatment for each subject, which was validated through each subject's actual eradication outcome.

Both previously reported and novel variants were identified from H. pylori sequencing results. Concurrently, five CYP2C19 homozygous extensive metabolizers and three CYP3A4 intermediate metabolizers were identified. Among the total of 12 subjects, clarithromycin triple therapy was suggested for five subjects, bismuth quadruple therapy was suggested for six subjects, and rifabutin triple therapy was suggested for one subject by following the customized framework criteria. The treatment suggestion for nine of the 12 subjects was consistent with the treatment that each subject achieved eradication with.

Applying the methodology using the NGS-PHET and customized framework helps to perform eradication treatment quickly and effectively in most patients with antibiotic-resistant H. pylori strains, and is also useful in research to find novel antibiotic-resistance candidates.

Helicobacter pylori (H. pylori) infection can cause extensive apoptosis of gastric epithelial cells, serving as a critical catalyst in the progression from chronic gastritis, gastrointestinal metaplasia, and atypical gastric hyperplasia to gastric carcinoma. Prompt eradication of H. pylori is paramount for ameliorating the pathophysiological conditions associated with chronic inflammation of the gastric mucosa and the primary prevention of gastric cancer. Acacetin, which has multifaceted pharmacological activities such as anti-cancer, anti-inflammatory, and antioxidative properties, has been extensively investigated across various domains. Nevertheless, the impact and underlying mechanisms of action of acacetin on H. pylori-infected gastric mucosal epithelial cells remain unclear.

To explore the defensive effects of acacetin on apoptosis in H. pylori-infected GES-1 cells and to investigate the underlying mechanisms.

GES-1 cells were treated with H. pylori and acacetin in vitro. Cell viability was assessed using the CCK-8 assay, cell mortality rate via lactate dehydrogenase assay, alterations in cell migration and healing capacities through the wound healing assay, rates of apoptosis via flow cytometry and TUNEL staining, and expression levels of apoptosis-associated proteins through western blot analysis.

H. pylori infection led to decreased GES-1 cell viability, increased cell mortality, suppressed cell migration, increased rate of apoptosis, increased expressions of Bax and cle-caspase3, and decreased Bcl-2 expression. Conversely, acacetin treatment enhanced cell viability, mitigated apoptosis induced by H. pylori infection, and modulated the expression of apoptosis-regulatory proteins by upregulating Bcl-2 and downregulating Bax and cleaved caspase-3.

Acacetin significantly improved GES-1 cell viability and inhibited apoptosis in H. pylori-infected GES-1 cells, thereby exerting a protective effect on gastric mucosal epithelial cells.

Helicobacter pylori (H. pylori) infection is currently widespread throughout the world. Bismuth-containing quadruple therapy is widely used, but it has rarely been associated with interstitial lung disease.

We described six cases with similar clinical symptoms and typical pulmonary interstitial imaging changes during anti-H. pylori therapy, usually on Days 7-12 following treatment. Anti-H. pylori infection treatment was discontinued when it was suspected to be the cause of the clinical symptoms, and all of the patients accepted observation therapy. All of them had a favorable outcome, the clinical symptoms returned to normal almost 1 week later, and the chest computed tomography (CT) scan images showed remarkable absorption 4 weeks later.

Drug interactions could be the cause, and the most likely drug was furazolidone. All of the patients recovered quickly after drug discontinuation, and low-dose steroid may help shorten the recovery time.

Vonoprazan, a potassium-competitive acid blocker, has demonstrated greater potency and a longer duration of acid suppression when compared to the proton pump inhibitors. However, data regarding the comparison between vonoprazan-based triple therapy with standard treatment for first-line Helicobacter pylori treatment are limited. This study aimed to compare the efficacy between 7-day vonoprazan-based triple therapy with high-dose amoxicillin (VAC-7) and 14-day extended sequential therapy (S-14).

This was a single-center prospective randomized controlled trial following a noninferiority design. Subjects over 20 years old with confirmed H. pylori infection were enrolled prospectively from Fu Jen Catholic University Hospital. They were randomly assigned to the VAC-7 or S-14 group. The primary endpoint was the eradication rate in first-line treatment, evaluated by urea breath test, with noninferiority determined using the Farrington-Manning method. The secondary outcome included adverse effect rates and compliance, assessed through self-administered questionnaires.

Between December 2021 and June 2023, a total of 628 patients were recruited. The eradication rates by per-protocol analysis and intention-to-treat analysis were 88.6%/81.8% for VAC-7 and 90.3%/81.4% for S-14, respectively. The VAC-7 was non-inferior to S-14 in terms of ITT analysis. Subjects experienced fewer incidences of nausea, anorexia, dizziness, fatigue, and any severe adverse events in the VAC-7 group. Compliance was higher in the VAC-7 group, with 94% taking all the pills correctly.

Our findings supported the use of 7-day vonoprazan triple therapy with high-dose amoxicillin as the standard first-line treatment for H. pylori infection.

ClinicalTrials.gov identifier: NCT05371249.

Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection.

This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13C-urea breath test was performed to evaluate H. pylori eradication.

In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups.

As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions.

ClinicalTrials.gov identifier: NCT05431075.

Helicobacter pylori is a type of Gram-negative bacteria belonging to the Proteobacteria phylum which is known to cause gastrointestinal disorders such as gastritis and gastric ulcers. Its treatment is based on current eradication regimens, which are composed of combinations of antibiotics such as clarithromycin, metronidazole, levofloxacin and amoxicillin, often combined with a proton pump inhibitor (PPI). With the development of sequencing technologies, it has been demonstrated that not only does the colonization of the gastric and gut environment by H. pylori cause microbial changes, but also the treatment regimens used for its eradication have a significant altering effect on both the gastric and gut microbiota. Here, we review current knowledge on microbiota modulations of current therapies in both environments. We also summarize future perspectives regarding H. pylori infection, the integration of probiotics into therapy and what challenges are being faced on a global basis when we talk about eradication.

Background: H. pylori (Helicobacter pylori) infections typically occur in early childhood. Although the prevalence of H. pylori in children is lower than that in adults, the eradication rate of this infection in children is relatively low because of resistance. In this study, we analyzed personalized treatment strategies to achieve treatment goals based on H. pylori resistance characteristics. This retrospective single-center study was conducted between January 2019 and December 2022 and enrolled 1,587 children who presented with upper gastrointestinal symptoms and underwent endoscopy. H. pylori culturing and antimicrobial susceptibility testing were performed. Results: Culture-positive results for H. pylori were obtained in 535 children. The resistance rates to clarithromycin (CLA), metronidazole (MET), and levofloxacin (LEV) were 39.8%, 78.1%, and 20.2%, respectively. None of the isolates were resistant to tetracycline (TET), amoxicillin (AMO), or furazolidone (FZD). Double resistance rates to CLA + MET, CLA + LEV, and MET + LEV were 19.1%, 3.0%, and 5.8%, respectively. Notably, triple-resistant to CLA + MET + LEV was 9.7%. Based on susceptibility tests, individualized triple therapy [proton pump inhibitor (PPI) +AMO + CLA/MET] was selected for 380 children with H. pylori sensitive to MET and/or CLA. In 155 children resistant to CLA and MET, bismuth-based quadruple therapy was recommended; for unable to receive bismuth, concomitant therapy was recommended for 14 children (<8 years of age); triple therapy with TET was recommended for 141 children (>8 years of age), with 43 children (>14 years of age) requiring FZD rather than TET. Conclusion: Resistance to H. pylori in Chinese children was relatively poor. Personalized therapy regimens should be based on susceptibility tests and avoided factors associated with treatment failure.

Helicobacter pylori infection is a major global health concern, and its management has witnessed a revolutionary shift with the emergence of antibiotic resistance. In this review, I explore the mechanisms of H. pylori antibiotic resistance and highlight the critical need for susceptibility-based eradication treatments. The increasing prevalence of antibiotic-resistant strains requires innovative approaches to combat this resilient pathogen. I also delve into the importance of mass screening as a preventive strategy for early detection and intervention, describing my experience in Bhutan. Additionally, I explore promising alternatives, such as vaccination. The aim of this review is to provide insight into the evolving landscape of H. pylori treatment and highlight the need for a paradigm shift in the approach to combating this persistent bacterial infection.

The lack of specific symptoms of gastric cancer (GC) causes great challenges in its early diagnosis. Thus it is essential to identify the risk factors for early diagnosis and treatment of GC and to improve the survival rates.

To assist physicians in identifying changes in the output of publications and research hotspots related to risk factors for GC, constructing a list of key risk factors, and providing a reference for early identification of patients at high risk for GC.

Research articles on risk factors for GC were searched in the Web of Science core collection, and relevant information was extracted after screening. The literature was analyzed using Microsoft Excel 2019, CiteSpace V, and VOSviewer 1.6.18.

A total of 2514 papers from 72 countries and 2507 research institutions were retrieved. China (n = 1061), National Cancer Center (n = 138), and Shoichiro Tsugane (n = 36) were the most productive country, institution, or author, respectively. The research hotspots in the study of risk factors for GC are summarized in four areas, namely: Helicobacter pylori (H. pylori) infection, single nucleotide polymorphism, bio-diagnostic markers, and GC risk prediction models.

In this study, we found that H. pylori infection is the most significant risk factor for GC; single-nucleotide polymorphism (SNP) is the most dominant genetic factor for GC; bio-diagnostic markers are the most promising diagnostic modality for GC. GC risk prediction models are the latest current research hotspot. We conclude that the most important risk factors for the development of GC are H. pylori infection, SNP, smoking, diet, and alcohol.

The efficacy and safety of potassium-competitive acid blockers (P-CABs) in the eradication of Helicobacter pylori (Hp) remains controversial when compared with proton pump inhibitors (PPIs).

The current study set out to compare the differences in the eradication rate and adverse reactions between eradication regimens based on P-CAB or PPI drugs and the differences between the vonoprazan-based and the tegoprazan-based regimens to explore the efficacy and safety of different Hp eradication regimens.

Databases including PubMed, EMBASE, Cochrane Library, and WOS were searched from the inception of these databases up to July 2023, and eligible randomized controlled trials (RCTs) were included. The outcome measures were the eradication rate and the incidence of adverse reactions of different regimens in treating Hp. The results were estimated as relative risk (RR) and its 95% confidence interval (CI), and R 4.2.1 software was used to perform the network meta-analysis (NMA).

A total of 20 studies were included in the analysis, involving 5815 patients with Hp. In terms of eradication rate, the 2-week vonoprazan-based triple regimen (V-Tri-2w) was the best, which was superior to the 2-week PPI-based quadruple regimen [P-Qua-2w, RR = 0.9, 95% CI: (0.85-0.95)] and the 1-week tegoprazan-based triple regimen [T-Tri-1w, RR = 0.79, 95% CI: (0.64-0.97)]; the 2-week tegoprazan-based quadruple regimen (T-Qua-2w) was superior to the 1-week PPI-based triple regimen [P-Tri-1w, RR = 0.82, 95% CI: (0.67-0.99)], and there was no difference between the remaining tegoprazan-based regimens and the PPI-based or vonoprazan-based regimens. In terms of the incidence of adverse reactions, the 2-week vonoprazan-based binary regimen (V-Bi-2w) was lower than that of the 2-week PPI-based quadruple regimen [P-Qua-2w, RR = 1.98, 95% CI: (1.57-2.52)]; there was no significant difference between 1 and 2 weeks for each regimen, such as the vonoprazan-based triple regimen [RR = 1.11, 95% CI: (0.82-1.52)].

In the eradication treatment of Hp, the efficacy and safety of vonoprazan-based regimens are generally better than those of PPI-based regimens. Among them, the V-Tri-2w regimen has the highest eradication rate and may be the preferred choice for Hp eradication.

Helicobacter pylori eradication failure influences its antibiotic resistance.

This study aimed to evaluate the effect of previous treatment failures on it, including the changes in the antibiotic resistance rates, minimal inhibitory concentration (MIC) distributions, and resistance patterns.

This single-center retrospective study included 860 primary isolates and 247 secondary isolates. Antibiotic susceptibility testing was performed for amoxicillin, metronidazole, clarithromycin, levofloxacin, furazolidone, tetracycline, and rifampicin. The demographic data and detailed regimens were collected.

The primary resistance rates to amoxicillin, metronidazole, clarithromycin, levofloxacin, tetracycline, rifampin, and furazolidone were 5.93%, 83.84%, 28.82%, 26.28%, 0.35%, 1.16%, and 0%, while secondary were 25.10%, 92.31%, 79.76%, 63.16%, 1.06%, 3.19%, and 0%, respectively. The resistance rates to amoxicillin, metronidazole, clarithromycin, and levofloxacin increased significantly with the number of treatment failures accumulated, and showed a linear trend. The proportion of primary and secondary multidrug-resistant (MDR) isolates were 17.79% and 63.16%, respectively. The MIC values of amoxicillin, clarithromycin, and levofloxacin were elevated significantly with medication courses increased.

The prevalence of amoxicillin, clarithromycin, levofloxacin, and metronidazole resistance would increase rapidly following first-line treatment failure, as well as the MIC values of them. Clinicians should pay great attention to the first-line treatment to cure H. pylori infection successfully.

Standard triple therapy is commonly prescribed Helicobacter pylori eradication regimen in Europe. However, the world is witnessing declines in eradication success. It is crucial to find better treatment options.

To evaluate efficacy, compliance and side effects of H. pylori eradication treatment by adding Saccharomyces boulardii .

We conducted a randomized clinical trial within the GISTAR cohort, consisting of healthy individuals aged 40-64 years. Participants were administered clarithromycin-containing triple therapy (clarithromycin 500 mg, amoxicillin 1000 mg, esomeprazole 40 mg) twice daily. Randomization was applied based on two factors: 1)addition of Saccharomyces boulardii CNCM I-745 500 mg BID or not; 2)treatment duration of 10 or 14 days. Treatment completion and adverse events were assessed via telephone interview 21-28 days after medication delivery. The efficacy was evaluated using a 13C-urea breath test (UBT) six months after treatment.

Altogether 404 participants were enrolled; data on adverse events were available from 391. Overall, 286 participants received follow-up UBT. Intention-to-treat analysis revealed higher eradication rates for 10-day probiotic treatment (70.8% vs. 54.6%, P  = 0.022), but not for 14-day. Probiotic subgroups combined showed non-significantly higher efficacy in per-protocol analysis (90.6% vs. 85.0%, P  = 0.183). S. boulardii reduced the frequency of adverse events ( P  = 0.033) in 14-day regimen, particularly treatment-associated diarrhea ( P  = 0.032). However, after the adjustment to control Type I error, results lost their significance.

Addition of S. boulardii to 14-day clarithromycin-containing triple regimen non-significantly lowers the likelihood of diarrhea and does not increase the eradication rate.

To assess the effects of Helicobacter pylori (HP) eradication with an omeprazole, clarithromycin, amoxicillin, and metronidazole (OCAM) regimen on the metabolic profile and weight loss 12 months after bariatric surgery (BS).

Retrospective analysis of a prospective cohort of patients with morbid obesity undergoing BS. HP presence was tested preoperatively by gastric biopsy and treated with OCAM when positive. Short-term metabolic outcomes and weight loss were evaluated.

HP infection was detected in 75 (45.7%) of the 164 patients included. OCAM effectiveness was 90.1%. HP-negative patients had a greater reduction in glucose levels at 3 (-14.6 ± 27.5 mg/dL HP-treated vs -22.0 ± 37.1 mg/dL HP-negative, p=0.045) and 6 months (-13.7 ± 29.4 mg/dL HP-treated vs -26.4 ± 42.6 mg/dL HP-negative, p= 0.021) and greater total weight loss (%TWL) at 6 (28.7 ± 6.7% HP-treated vs 30.45 ± 6.48% HP-negative, p= 0.04) and 12 months (32.21 ± 8.11% HP-treated vs 35.14 ± 8.63% HP-negative, p= 0.023).

Preoperative treatment with OCAM has been associated to poorer glycemic and weight loss outcomes after BS. More research is needed on the influence of OCAM on gut microbiota, and in turn, the effect of the latter on metabolic and weight loss outcomes after BS.

Background and aim: We conducted an equivalence trial of quadruple non-bismuth "concomitant" and "hybrid" regimens for H. pylori eradication in a high clarithromycin resistance area. Methods: There were 321 treatment-naïve H. pylori-positive individuals in this multicenter clinical trial randomized to either the hybrid (esomeprazole 40 mg/bid, amoxicillin 1 g/bid for 7 days, then 7 days esomeprazole 40 mg/bid, amoxicillin 1 g/bid, clarithromycin 500 mg/bid, and metronidazole 500 mg/bid) or the concomitant regimen (all medications given concurrently bid for 10 days). Eradication was tested using histology and/or a 13C-urea breath test. Results: The concomitant regimen had 161 patients (90F/71M, mean 54.5 years, 26.7% smokers, 30.4% ulcer) and the hybrid regimen had 160 (80F/80M, mean 52.8 years, 35.6% smokers, 31.2% ulcer). The regimens were equivalent, by intention to treat 85% and 81.8%, (p = 0.5), and per protocol analysis 91.8% and 87.8%, (p = 0.3), respectively. The eradication rate by resistance, between concomitant and hybrid regimens, was in susceptible strains (97% and 97%, p = 0.6), clarithromycin single-resistant strains (86% and 90%, p = 0.9), metronidazole single-resistant strains (96% and 81%, p = 0.1), and dual-resistant strains (70% and 53%, p = 0.5). The side effects were comparable, except for diarrhea being more frequent in the concomitant regimen. Conclusions: A 14-day hybrid regimen is equivalent to a 10-day concomitant regimen currently used in high clarithromycin and metronidazole resistance areas. Both regimens are well tolerated and safe.

Increasing antibiotic resistance is the primary reason for treatment failure of Helicobacter pylori (H. pylori) infection. To enhance the eradication rate, minimize the development of secondary resistance, and alleviate the socioeconomic burden, it is crucial to select H. pylori-sensitive antibiotics carefully. Furazolidone has been used for H. pylori eradication in developing countries for decades due to its affordability and low resistance rate. Numerous studies have demonstrated that furazolidone-containing regimens are more efficacious than those containing other antibiotics, as both first- and second-line therapies, and are also well tolerated. However, utility of furazolidone is restricted or not optimal in certain countries due to its infrequent but potentially severe adverse effects. The decision to discontinue usage of furazolidone because of concerns regarding adverse effects may be misguided. Here we comprehensively reviewed the studies on furazolidone at different dosages and treatment durations for H. pylori eradication. Further research on the mechanisms of action and clinical trials of furazolidone are of great practical importance.

Vonoprazan, a novel acid suppressant, has recently emerged as a regimen for eradicating Helicobacter pylori. However, uncertainties exist about the effectiveness and safety of VPZ-based regimens compared with those of bismuth-based quadruple therapy in eradicating H. pylori. The present meta-analysis was performed to compare the effectiveness and safety of vonoprazan-based regimens with those of bismuth quadruple therapy in eradicating H. pylori.

All randomized controlled trials and non-randomized controlled trials comparing the vonoprazan-based therapy with the bismuth quadruple therapy were included in this meta-analysis. Information was also extracted by two evaluators, and if heterogeneity existed, a random-effects model was used to calculate the combined relative ratio and 95% confidence interval; otherwise, a fixed-effects model was used. And subgroup analyses were performed to explore the sources of heterogeneity.

A total of 10 studies, comprising 2587 patients were included in the meta-analysis. The results showed that the combined eradication rate of patients treated with the vonoprazan-based regimen was significantly higher than that of patients treated with bismuth quadruple therapy, in both intention-to-treat and per-protocol analyses, and the differences were statistically significant. Among the intention-to-treat analyses results: (90.28% vs. 83.64% [odds ratio (OR) = 1.85, 95% confidence interval (CI) (1.27, 2.70), p = 0.001]); in the per-protocol analyses: (94.80% vs. 89.88%, [OR = 2.25, 95% CI (1.37, 3.69), p = 0.001]). The occurrence of adverse events was significantly lower in patients treated with vonoprazan-based regimens than in those treated with bismuth quadruple therapy, (14.50% vs. 25.89%, [OR = 0.49, 95% CI (0.32, 0.75), p = 0.001]).

For eradicating H. pylori, vonoprazan-based regimens are remarkably advantageous over bismuth quadruple therapy. Furthermore, vonoprazan-based regimens exhibit a lower rate of adverse events than bismuth quadruple therapy.