Recent studies have shown a noticeable increase in global Helicobacter pylori (H. pylori) resistance, with clarithromycin resistance surpassing 15% in various areas. However, inadequate epidemiological monitoring, especially in developing countries, and the absence of uniform testing methods lead to discrepancies between regions and a possible underestimation of resistance levels. The complexity of treating H. pylori is driven by its highly dynamic genome, which is prone to frequent mutations contributing to phenotypical resistance. The usual course of action in empirical treatment involves using a combination of various drugs simultaneously, leading to significant resistance selection pressure and potential side effects. The emergence of H. pylori strains resistant to multiple drugs is closely tied to failures in first-line treatment, highlighting the need to prevent further resistance by using optimal initial empirical therapy or regimens guided by antibiotic susceptibility testing, requiring a collection of mixed samples and multiple isolates for accurate assessment. The emergence of new treatments like potassium-competitive acid blockers offers a hopeful approach to decrease antimicrobial usage while still ensuring effectiveness in comparison to traditional therapies with proton pump inhibitors. Additionally, the use of probiotics is under investigation to identify specific strains and formulations that may mitigate therapy-associated adverse effects.

Tegoprazan, a new class of drugs, is a potassium-competitive acid blocker (P-CAB) that inhibits gastric H+/K+-ATPase through a different mechanism than proton pump inhibitor. Tetracycline also has anti-Helicobacter pylori properties. However, only a few randomized controlled trials (RCTs) have investigated the efficacy of tegoprazan and tetracycline-containing quadruple therapy (TTQT) for treating H. pylori infections, which this RCT explored.

This multicenter RCT included treatment-naïve adults with H. pylori infection who received 7 or 14 days of TTQT (50-mg tegoprazan, 220-mg bismuth potassium citrate, and 1000-mg amoxicillin twice daily with 500-mg tetracycline four times daily). The primary outcome was the eradication rate; secondary endpoints included the incidence of adverse events, treatment compliance, and regimen costs.

The study included 258 patients. The eradication rates in the 7- and 14-day groups were 90.70% (117/129, 95% confidence interval [CI]: 83.98%-94.89%) and 91.47% (118/129, 95% CI: 84.90%-95.45%), respectively, in the intention-to-treat analysis (difference: -0.78%; -7.01%-8.58%; noninferiority p < 0.001); 92.86% (117/126, 95% CI: 86.50%-96.48%) and 93.65% (118/126, 95% CI: 87.47%-97.02%), respectively, in the modified intention-to-treat analysis (difference: 0.79%; 95% CI: -6.36%-7.99%; noninferiority p < 0.001); and 94.35% (117/124, 95% CI: 88.29%-97.50%) and 95.12% (117/123, 95% CI: 89.24%-98.00%), respectively, in the per-protocol analysis (difference: -0.77%; 95% CI: -5.91%-7.48%; noninferiority p < 0.001). Significantly fewer adverse events occurred in the 7-day group than in the 14-day group (22.48% vs. 35.67%, p = 0.020). Treatment compliance did not differ between the two groups.

The 7- and 14-day TTQT efficacies for the first-line treatment of H. pylori infection were comparable, and fewer adverse effects occurred in the 7-day group. This trial has been registered at Clinical Trials.gov (NCT05997433).

Helicobacter pylori ( H. Pylori ) is considered a main causative organism of gastric ulcers, gastric cancer and duodenal ulcers. The current treatment relies on a combination of antimicrobial agents and acid suppressant agents, but the eradication effect is not satisfactory. To clarify the concentration of antibiotics at the lesion site, we investigate the clinical efficacy and drug tissue distribution of the combination therapy of furazolidone and tetracycline in eradicating H. Pylori.

Patients with H. pylori infection (n = 60) were randomized to either group A or B. Bismuth potassium citrate capsules 220 mg, omeprazole enteric-coated capsules 20 mg, amoxicillin capsules 1000 mg, each twice per day, and furazolidone tablets 500 mg were administered to group A. Group B was treated with bismuth potassium citrate capsules 220 mg, omeprazole enteric-coated capsules 20 mg, amoxicillin capsules 1000 mg, and tetracycline tablets 500 mg each twice per day for 2 weeks. The serum and gastric juice, gastric antrum, gastric horn, and gastric body samples were taken under a gastroscope on the 14th day. The antimicrobial concentrations in serum and tissue samples were determined by high-performance liquid chromatography.

In the negative group of furazolidone, the concentrations of gastric antrum, gastric body, and gastric angle were significantly higher than those in the positive group ( P = 0.017, 0.015, and 0.028). The concentrations of furazolidone in gastric fluid, gastric antrum, gastric angle, and gastric body were ∼421 times, 82 times, 17 times, and 51 times higher than those in serum, respectively. The concentrations of tetracycline in the serum and gastric angle of the tetracycline negative group were significantly higher than those in the positive group ( P = 0.036 and 0.042), and the tetracycline concentrations in the gastric horn and gastric body were about 4 and 6 times higher than those in the serum, respectively. The concentration of amoxicillin in group B was higher than that in group A, especially in serum, gastric juice, gastric angle, and gastric body ( P < 0.05).

Furazolidone is mainly concentrated and sequentially distributed in gastric juice, gastric antrum, and gastric body tissue, and tetracycline is mainly distributed in serum, gastric angle, and gastric body, whereas amoxicillin is mainly distributed in serum, gastric juice, gastric angle, and gastric body. Improving the concentration and tissue distribution of antibacterial drugs in the human gastric mucosa is the key to ensuring the ideal eradication rate of quadruple therapy.

In this study, the main goal was to find a statistically significant difference between eradication treatment plans that used azithromycin and clarithromycin in triple and quadruple eradication plans.

This retrospective, single-center, observational, non-funded Helicobacter pylori management study examined patients who visited our institutional gastroenterology clinic at the King Hussein Medical Centre in the Royal Medical Services, Amman, Jordan, from January 2023 to May 2024. The most common treatment (TRT) courses are 7 or 10-14 days, so this study divided the therapy length into two categories. We also divided proton pump inhibitors (PPIs) into low-standard dose intensity (omeprazole 20-40 mg/day) and high-dose intensity (80 mg/day). Patients received six TRT regimens. The study aimed to eradicate H. pylori with a negative stool antigen test after six weeks post-TRT and two weeks without PPIs. Clarithromycin and azithromycin were reference macrolides for TRT. Azithromycin-based TRT covered IV-VI, while clarithromycin-based TRT covered I-III. The chi-square test was used to quantify TRT I-II proportional differences in patient variables. Association coefficients, odd ratios for TRT success, prediction variability range, and H. pylori eradication sensitivity indices based on macrolides-based TRT I-II, TRT length categories, PPI intensity doses, and patients' adherence rating scale were extracted using multiple logistic regression.

Our gastroenterology unit tested 1076 patients. About 49.3% (530 patients) were female and 50.7% (546 patients) were male. The majority of patients, 78.2% (841), were under 60, while 21.8% (235) were 60 or older. Patients were given six eradication regimens (Regimens I-VI) with macrolides (clarithromycin or azithromycin). Most TRT durations were 7-14 days. We used multiple logistic regression. We considered patient adherence rates as confounding factors. Using azithromycin instead of clarithromycin has a statistically significant impact (1.780 (95% CI; 1.378-2.299).

Azithromycin can be a reasonable substitute for clarithromycin in triple or quadruple therapy eradication regimens for H. pylori infection.

The eradication of Helicobacter pylori (H. pylori) is crucial due to its rising prevalence and increasing resistance. Bismuth-containing quadruple therapies (BcQTs) have been proposed as a viable treatment option; however, the optimal duration for it remains contentious. This systematic review and meta-analysis aimed to compare the clinical efficacy of short-term BcQT (defined as 7 or 10 days) with a standard 14-day course.

A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted for randomized controlled trials published in English until June 20, 2024. Eligibility criteria were applied to identify relevant studies. Summary risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for the included studies regarding eradication rates, adverse effects, and compliance. This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was previously registered in PROSPERO under registration number CRD42024547773.

This meta-analysis finally included 15 trials involving a total of 4505 patients. The eradication rates for short courses of BcQT were lower than those for the 14-day course (RR 0.96, 95% CI 0.93-0.99). However, the eradication rate for the 10-day therapy was comparable to that of the 14-day therapy (RR 0.98, 95% CI 0.95-1.00). Subgroup analyses of antibiotic combinations indicated that tetracycline and metronidazole combinations yielded similar H. pylori eradication rates in the 7-day versus the 14-day BcQT (RR 0.93, 95% CI 0.84-1.02). In the potassium-competitive acid blocker subgroup, the eradication rates remained similar across the 14-day group and the short-course treatment groups, whether evaluating the short-term treatment groups as a whole or the 7- and 10-day subgroups separately. Additionally, the adverse effects and compliance associated with the short course of BcQT were comparable to those of the 14-day therapy.

A 10-day course of BcQT may represent the optimal treatment duration. Nevertheless, the choice of antibiotic combination should be guided by the regional antibiotic resistance patterns of H. pylori, as combinations with lower resistance rates are more effective.

PROSPERO number: CRD42024547773.

Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori.

Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication.

The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups.

Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

Helicobacter pylori infection poses a significant health burden worldwide, and its virulence factor CagA plays a pivotal role in its pathogenesis.

In this study, the interaction between H. pylori-infected AGS cells and silver nanoparticles (AgNPs) was investigated, with a focus on the modulation of CagA-mediated responses, investigated by western blotting. Both, the dose-dependent efficacy against H. pylori (growth curves, CFU assay) and the impact of the nanoparticles on AGS cells (MTT assay) were elucidated.

AGS cells infected with H. pylori displayed dramatic morphological changes, characterized by elongation and a migratory phenotype, attributed to CagA activity. Preincubation of H. pylori with AgNPs affected these morphological changes in a concentration-dependent manner, suggesting a correlation between AgNPs concentration and CagA function.

Our study highlights the nuanced interplay between host-pathogen interactions and the therapeutic potential of AgNPs in combating H. pylori infection and offers valuable insights into the multifaceted dynamics of CagA mediated responses.

Due to the rapid development of antimicrobial resistance, the efficacy of most Helicobacter pylori eradication therapies have progressively decreased to an unacceptable level. Rifasutenizol (TNP-2198) is a new molecular entity with a synergistic dual mechanism of action currently under clinical development for the treatment of microaerophilic and anaerobic bacterial infections. We aimed to evaluate the safety, pharmacokinetics, and efficacy of rifasutenizol in healthy Chinese participants and patients with H pylori.

We conducted four clinical trials of rifasutenizol capsules in healthy participants (aged 18-55 years) and patients with asymptomatic H pylori infection (aged 18-65 years) in a clinical trial centre in Jilin province, China. Trial 1 was a phase 1, double-blind, randomised, placebo-controlled, single ascending dose study, in which participants were enrolled into one of seven rifasutenizol dose groups (50 mg, 100 mg, 200 mg, 400 mg, 600 mg, 800 mg, or 1000 mg) and were randomly assigned in a 4:1 ratio to study drug or placebo. Trial 2 was a phase 1, double-blind, randomised, placebo-controlled, multiple ascending dose study, in which patients were enrolled into one of three rifasutenizol dose groups (200 mg, 400 mg, or 600 mg) and were randomly assigned in a 3:1 ratio to study drug or placebo. Trial 3 was a phase 2a, open-label, randomised, multiple-dose, dose-finding study in which patients enrolled into one of four cohorts were randomly assigned in a 1:1:1:1 ratio to a rifasutenizol dual or triple regimen. Trial 4 was a phase 2b, open-label, randomised, multiple-dose, regimen exploration study, in which patients enrolled into one of five cohorts were randomly assigned in a 2:2:1:1:2 ratio to a rifasutenizol dual therapy, triple therapy, or a control cohort. Block randomisation (block size 4 or 8) was used in all four trials. The key primary endpoints for trials 1, 2, and 3 were the tolerability, safety, and pharmacokinetics of rifasutenizol. For trial 4, the primary endpoint was the eradication rate of H pylori. These four trials were registered at ClinicalTrials.gov (NCT06081699, NCT06081712, NCT06076681, and NCT06076694) and chinadrugtrials.org.cn (CTR20190734, CTR20192553, CTR20212050, and CTR20220625) and are completed.

Between May 9, 2019, and Sept 14, 2022, 78 healthy participants (trial 1: n=10 per cohort in a 4:1 rifasutenizol:placebo ratio; and an additional eight for the food-effect cohort) and 168 patients with asymptomatic H pylori infection (trial 2: n=16 per cohort in a 3:1 rifasutenizol:placebo ratio; trial 3: n=10 per cohort; trial 4: n=10 or n=20 per cohort) were enrolled in the four clinical trials. Single doses of rifasutenizol (50-1000 mg) and multiple doses of rifasutenizol (200 mg to 600 mg, twice a day), either as monotherapy or co-administered with rabeprazole and amoxicillin, showed favourable safety and tolerability profiles. Most adverse events were mild, and no serious adverse events were reported. Rifasutenizol demonstrated a linear pharmacokinetic profile over the dose range of 50-800 mg, and there were no apparent pharmacokinetic interactions between rifasutenizol and the co-administrated drugs. Food intake slightly elevated the area under the plasma concentration-time curve (AUC) of rifasutenizol, and the geometric mean of AUC from time 0 to the last timepoint with a quantifiable concentration (AUC0-t) and AUC from time 0 to infinity (AUC0-∞) in the fed state were 1·334 and 1·396 times of those in the fasted state, respectively. There was mild accumulation after continuous administration of rifasutenizol, and the Rac(AUC) of rifasutenizol 400 mg in the dual and triple regiments in trial 3 were 1·37 and 1·49, respectively. In trial 3, the eradication rates of H pylori with 200 mg, 400 mg, or 600 mg of rifasutenizol in combination with rabeprazole, twice a day for 14 days, were 0% (95% CI 0-31), 30% (7-65), and 40% (12-74), respectively, identifying rifasutenizol 400 mg as the effective dose. In trial 4, H pylori eradication rates with the triple regimen in cohort A (400 mg rifasutenizol, 20 mg rabeprazole sodium, and 1 g amoxicillin) twice a day for 14 days was 95% (95% CI 74-100), and triple therapy (600 mg rifasutenizol, 20 mg rabeprazole sodium, and 1 g amoxicillin) three times a day for 7 days was 100% (69-100).

Rifasutenizol monotherapy and combination therapy was generally safe and well tolerated in healthy participants and patients with H pylori infection. A triple regimen of 400 mg rifasutenizol capsules, 20 mg rabeprazole sodium enteric-coated tablets, and 1 g amoxicillin capsules twice a day for 14 days showed promising efficacy as a new treatment regimen for H pylori infection.

TenNor Therapeutics and National Natural Science Foundation of China.

For the Chinese translation of the abstract see Supplementary Materials section.

Concomitant therapy (CT) and bismuth quadruple therapy (BQT) are recommended in geographical areas with high clarithromycin resistance for Helicobacter pylori (H. pylori) eradication. We compared CT and BQT as the first lines of treatment in a randomized controlled trial. Consecutive patients with H. pylori diagnosed by concordance of both a urea breath test and histology were recruited. For BQT, patients received 3 PyleraTM capsules q.i.d.; for CT, 1000 mg of amoxicillin b.i.d, 500 mg of clarithromycin b.i.d and 500 mg of metronidazole b.i.d. As a proton pump inhibitor, 40 mg of pantoprazole b.i.d was administered. Both regimens lasted 10 days. In total, 46 patients received CT and 38 BQT. Both groups were comparable for age (p = 0.27) and sex (p = 0.36). We did not record any drop outs; therefore, the intention to treat and per protocol rates coincided. The most common symptoms were heartburn and post-prandial fullness, which were equally present in both groups. The success rate was 95.6% for CT and 100% for BQT (p = 0.56). Side effects were recorded in 23.9% and 31.6% of patients in the CT and BQT arms, respectively (p = 0.47). The most common ones were abdominal pain (8) and diarrhea (6). In conclusion, CT and BQT are equally effective in our area with high clarithromycin resistance, southern Italy, and showed comparable safety.

Bismuth quadruple therapy is currently consensus recommendation for first-line Helicobacter pylori (H. pylori) treatment; however, the optimal duration is unknown. We compared the efficacy of 10-day bismuth quadruple therapy with that of 14-day bismuth quadruple therapy for first-line eradication.

For our multicentre, parallel randomised, open-label, and non-inferiority study, we recruited H. pylori treatment-naïve patients from one medical centre and one teaching hospital in Taiwan. Patients were randomly assigned (1:1) to receive 10-day (PBMT-10) or 14-day (PBMT-14) bismuth quadruple therapy. The primary outcome was the eradication rate as determined by intention-to-treat (ITT) and per-protocol (PP) analyses. The eradication rates between the two groups were compared using a one-sided α value of 0.025 and a non-inferiority margin of 7%. The secondary outcomes were the rate of adverse effects. The trial is registered with ClincialTrials.gov (NCT04527055).

From August 3, 2020 to April 28, 2023, 313 H. pylori treatment-naïve patients (PBMT-10 = 157; PBMT-14 = 156) were enrolled. 35 patients were excluded from PP analyses. The eradication rates (95% CI) for PBMT-10 and PBMT-14 were respectively 92.4% (88.2%-96.5%) and 92.9% (88.9%-97.0%) by ITT analyses, and 97.9% (95.5%-100.0%) and 99.3% (97.8%-100.0%) by PP analyses. The eradication rates for PBMT-10 were non-inferior to those for PBMT-14 (absolute difference [lower boundary of the one-sided 97.5% CI] -0.6% [-6.7%], PNI = 0.020 in ITT analyses, -1.4% [-5.8%], PNI = 0.007 in PP analyses). The rates of overall adverse effects (54.1% versus 57.1%, P = 0.604) were similar between the two groups; nevertheless, the rates of dizziness (18.5% versus 34.0%, P = 0.003) and vomiting (4.5% versus 12.8%, P = 0.008) were lower in PBMT-10 than in PBMT-14.

The 10-day bismuth quadruple therapy was non-inferior to the 14-day therapy as a first-line treatment for eradicating H. pylori infection and had no different rates of overall adverse effects, but less serious adverse events in terms of dizziness and vomiting.

The National Science and Technology Council and Ministry of Health and Welfare, Taiwan.

Current global variations exist in Helicobacter pylori (H. pylori) eradication regimens. Triple therapy (TT), bismuth quadruple therapy (BQT), and high-dose dual therapy (HDDT) currently represent the predominant regimens. These regimens diverge in terms of treatment duration, the utilization of susceptibility testing, acid-inhibiting drug administration, and patient education. We conducted a comprehensive systematic literature review on these H. pylori treatment regimens. Our review aims to provide standardized treatment recommendations for H. pylori, reducing the risk of amalgamating findings from diverse eradication regimens. Recent research suggests that the optimal treatment duration for TT and BQT may be 14 and 10 days, respectively. Selecting the appropriate treatment duration for HDDT should rely on regional research evidence, and 14 days may be the optimal duration. The incorporation of susceptibility testing in TT is of paramount importance. In the case of BQT, the absence of susceptibility testing may be considered as an option, contingent upon cost and availability, and should be determined based on local antibiotic resistance patterns and the efficacy of empirical regimens. The type and dosage of acid-inhibiting drug would affect the efficacy of these regimens. Acid-inhibiting drugs should be selected and applied reasonably according to the population and therapies. Adequate patient education plays a pivotal role in the eradication of H. pylori. In regions with accessible local research evidence, the 10-day empirical BQT regimen may be considered a preferred choice for H. pylori eradication.

To compare the efficacy and tolerability of minocycline vs. tetracycline in bismuth-containing quadruple therapy for Helicobacter pylori (H. pylori) rescue treatment.

This study was a multi-center, randomized-controlled, non-inferiority trial. Refractory H. pylori-infected subjects with multiple treatment-failure were randomly (1:1) allocated to receive 14-day therapy with esomeprazole 20 mg b.i.d, bismuth 220 mg b.i.d, plus metronidazole 400 mg q.i.d and minocycline 100 mg b.i.d (minocycline group) or tetracycline 500 mg q.i.d (tetracycline group). Primary outcome was H. pylori eradication rate evaluated by 13C-urea breath test at least 6 weeks after the end of treatment. Antibiotic resistance was determined using E test method.

Three hundred and sixty-eight subjects were randomized. The eradication rates in minocycline group and tetracycline group were 88.0% (162/184, 95% CI 83.3-92.8%) and 88.6% (163/184, 95% CI 83.9-93.2%) in intention-to-treat analysis, 98.0% (149/152, 95% CI 95.8-100%) and 97.4% (150/154, 95% CI 94.9-99.9%) in per-protocol analysis, 93.1% (162/174, 95% CI 89.3-96.9%) and 93.1% (163/175, 95% CI 89.4-96.9%) in modified intention-to-treat analysis. Minocycline, tetracycline and metronidazole resistance rates were 0.7%, 1.4% and 89.6%, respectively. Non-inferiority of minocycline was confirmed (P < 0.025). Metronidazole resistance did not affect the efficacy of either therapy. The two therapies exhibited comparable frequencies of adverse events (55.4% vs. 53.3%); almost half of them were mild. Dizziness was the most common adverse events in the minocycline group.

Minocycline can be an alternative for tetracycline in bismuth-containing quadruple therapy for H. pylori empirical rescue treatment, irrespective of metronidazole resistance. However, relatively high incidence of adverse events in both regimens should be emphasized.