Background Favorable outcomes in treating H pylori infection using “dual therapy (proton pump inhibitor and amoxicillin four times daily)” have attracted widespread attention. However, there are few reports, and the study results lack agreement. This study aimed to compare the eradication rate, safety, and compliance of naïve‐treatment patients with H pylori infection on “dual therapy” with those on “triple plus bismuth (TPB) therapy.” Methods This is a non‐inferior randomized controlled trial conducted on 760 patients with H pylori infection. The participants were randomly assigned to two eradication groups: dual therapy (esomeprazole 20 mg and amoxicillin 750 mg four times daily) and TPB therapy (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg twice daily) for 14 days. Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed about 8 weeks after eradication to evaluate outcome. Antibiotic resistance and CYP2C19 polymorphism were determined. Results Compared with TPB therapy, dual therapy had significantly higher eradication rates in intention‐to‐treat (87.1% vs 80.5%, rate difference 6.6%), modified intention‐to‐treat (90.9% vs 85.5%, 5.5%) and per‐protocol (92.4% vs 87.8%, 4.7%) analyses, respectively. Adverse reactions in dual therapy group were significantly lower than TPB therapy group (17.6% vs 25.5%, P = .008), and dual therapy group had better compliance (96.3% vs 92.3%, P = .019). Antibiotic resistance and poor compliance were also associated with treatment failure. Conclusions Dual therapy (esomeprazole and amoxicillin four times daily) was non‐inferior to, and even superior to TPB therapy as first‐line H pylori eradication.

The eradication efficacies of RMAB therapy as first-line and second-line regimens were satisfactory with good compliance and safety in a region with high antibiotic resistance.

Background: Systematic reviews suggested that the eradication efficacy of PPIamoxicillin dual therapy is similar to that of other commonly used regimens. However, it might be affected by the medication frequency. Basic and clinical studies have shown that dual therapy administered four-times daily has a reliable pathophysiological basis and could achieve satisfactory efficacy. Therefore, a systematic review of RCTs of dual therapy and other regimens was conducted to clarify whether dual therapy is superior to guidelines recommended regimens. Materials and Methods:The RCTs comparing dual therapy with other regimens were subjected to meta-analysis to evaluate the eradication rate, adverse reactions, and compliance using a random-effects model. Results:Dual therapy administered four-times daily had a higher eradication rate than other regimens (intention-to-treat analysis: 89.7% vs 84.6%, OR: 1.52, 95%CI 1.08-2.14, p = 0.02; per-protocol analysis: 92.6% vs 88.2%, OR: 1.54, 95%CI 1.01-2.34, p = 0.04). In first-line therapy, according to intention-to-treat analysis, the eradication rate of dual therapy was higher than other regimens (89.8% vs 84.2%, OR: 1.63, 95%CI 1.02-2.61, p = 0.04). In per-protocol analysis, dual therapy showed better efficacy than others (92.9% vs 88.3%, OR: 1.68, 95% CI 0.98-2.89, p = 0.06), but not significantly. In salvage treatment, no significant difference was detected. The safety of dual therapy was significantly better than other regimens (19.6% vs 36.7%, p < 0.01), but no difference was observed in compliance (p = 0.58). Conclusion:PPI-amoxicillin dual therapy administered four-times daily has better efficacy and safety in H. pylori eradication than current guidelines recommended regimens, especially in first-line therapy, and mainly in Asia.

Background:The impact of probiotics on non-Helicobacter pylori gastric microbiota and its role in microbial restoration after eradication were relatively unknown. We aimed to explore the effect of H. pylori eradication and probiotic intervention on gastric microbiota in young adults.Methods: Fifty-six H. pylori-negative and 95 H. pylori-positive subjects aged 19-30 were included in this study. H. pylori-infected individuals were randomly assigned to quadruple therapy, probiotics supplemented quadruple therapy, or probiotics monotherapy group. Gastric mucosa and gastric juice samples were collected before and 2 months after treatment for 16SrRNA gene sequencing. Results:The gastric microbial community structure and composition differed from H. pylori-negative subjects 2 months after successful H. pylori eradication. The α diversity of gastric mucosal microbiota significantly increased and was higher than H. pylorinegative subjects, while the α diversity of gastric juice microbiota decreased and was lower than the H. pylori-negative. After probiotics supplemented eradication treatment, Bifidobacterium was enriched in gastric mucosa, Lactobacillus was enriched in gastric juice, potentially pathogenic bacteria such as Fusobacterium and Campylobacter decreased, and the microbial diversity was closer to that of H. pylori-negative subjects compared to quadruple therapy group. Probiotics monotherapy significantly altered the diversity, community structure, and composition of gastric microbiota but showed no advantage in H. pylori inhibition and upregulating beneficial bacteria such as Bifidobacterium and Lactobacillus and related metabolism pathways. Certain potentially pathogenic bacteria such as Fusobacterium increased after probiotic monotherapy. Conclusion:H. pylori eradication significantly disrupted gastric microbiota in young adults and could not be restored in a short time. Probiotics supplementation partially helped restore the gastric dysbiosis caused by eradication therapy, but it might be unnecessary for H. pylori-infected young adults to take probiotics alone.

Background: Helicobacter pylori eradication in penicillin-allergic patients is challenging. The effective regimen is lacking in areas with high antibiotic resistance and tetracycline unavailable. Minocycline, cefuroxime, and full-dose metronidazole are promising drugs. Aims:To compare the eradication rate, safety, and compliance among three new bismuth quadruple therapies for first-line H. pylori eradication in penicillin-allergic patients.Methods: This randomized trial was conducted on 450 naive patients with H. pylori infection and penicillin allergy. The 14-day minocycline-metronidazole-containing (minocycline 100 mg twice daily and metronidazole 400 mg four times/day), minocycline-cefuroxime-containing (minocycline 100 mg twice daily and cefuroxime 500 mg twice daily), and cefuroxime-metronidazole-containing (cefuroxime 500 mg twice daily and metronidazole 400 mg four times/day) bismuth quadruple therapies were randomly assigned to the participants. Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed 4-8 weeks after eradication to evaluate outcome. Results:The differences of eradication rates in either intention-to-treat (84.0%, 82.7%, and 23 82.0%, p = .896) or per-protocol (91.7%, 90.9%, and 88.2%, p = .599) analysis among minocycline-metronidazole, minocycline-cefuroxime, and cefuroximemetronidazole-containing bismuth quadruple therapies were statistically insignificant.The incidence of adverse events (35.1%, 22.6%, and 28.9%) and compliance (90.5%, 91.8%, and 91.9%) were similar. Taste distortion, nausea, and anorexia were more common in metronidazole-containing regimens, and dizziness was more common in minocycline-containing regimens. The allergy was rare (~3%). Conclusions:The efficacies of three bismuth quadruple therapies containing minocycline, cefuroxime, and full-dose metronidazole (pairwise) for first-line H. pylori eradication in penicillin-allergic patients were similarly satisfactory with relatively good safety and compliance. The study was registered in the Chinese Clinical Trials Registration (ChiCTR1900023702). How to cite this article: Zhang Y, Suo B, Tian X, et al. New regimens as first-line eradication therapy for Helicobacter pylori infection in patients allergic to penicillin: A randomized

Esomeprazole, bismuth, levofloxacin, and amoxicillin or cefuroxime achieved similar and relatively satisfactory cure rates, safety, and compliance in first-line H. pylori eradication. Cefuroxime may be a good alternative medicine for eradication instead of amoxicillin for the patients unsuitable to take penicillin.

Background: Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori (H. pylori) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens. Methods: This randomized controlled trial was conducted on 434 nave patients with H. pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 48 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t-test for continuous variables. Results: As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs. 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs. 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs. 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs. 88/214 [41.1%]) and compliance (195/215 [90.7%] vs. 192/214 [89.7%]) were similar between the two groups. Conclusion: The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H. pylori eradication with similar safety and compliance. Trial registration: ClinicalTrials.gov, ChiCTR 1900023646.

Background: It has not been fully confirmed whether the detection of Helicobacter pylori resistance gene mutation can replace antibiotic drug sensitivity test to guide the clinical individualized treatment. Therefore, we have studied this aspect and discussed the application value of antibiotic sensitivity gene test. Materials and Methods: The biopsy specimen of gastric mucosa from the patients examined by endoscopy and positive for rapid urease test were collected continuously for histopathological analysis, H. pylori culture, antibiotic drug sensitivity test (E-test drug sensitivity test), and antibiotic sensitivity gene test (high-throughput nucleotide sequencing). The participants received triple plus bismuth solution eradication treatment (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, twice daily for 14 days) for follow-up, and the eradication effect was determined. Results: The 551/602 subjects, who met the inclusion criteria, were subjected to culture for H. pylori and antibiotic drug sensitivity determination; among them 506 were cultured successfully. The results showed that the resistance rates of H. pylori were 38.9% for clarithromycin and 31.0% for levofloxacin. In 489 H. pylori strains, the mutations were detected in clarithromycin and levofloxacin resistance genes, indicating the genotype resistance. The resistance genes of clarithromycin and levofloxacin were consistent with phenotype resistance with respect to sensitivity (81.2% and 69.7% for clarithromycin and levofloxacin, respectively) and specificity (88.9% and 93.7% for clarithromycin and levofloxacin, respectively). The eradication rate of H. pylori in the clarithromycin-resistant group was significantly lower than that in the sensitive group (ITT: 52.1% vs 85.0%, P < 0.001). Conclusion:A correlation was established between the resistance genes of clarithromycin and levofloxacin and their phenotypic resistance and clinical efficacy. The detection of H. pylori resistance genes has a good clinical application prospect.