A Randomized Controlled Trial Shows that both 14-Day Hybrid and Bismuth Quadruple Therapies Cure Most Patients with Helicobacter pylori Infection in Populations with Moderate Antibiotic Resistance

Abstract

Hybrid therapy is a novel two-step treatment achieving a high eradication rate for infection. Currently, whether this new therapy achieves a higher eradication rate than bismuth quadruple therapy remains an unanswered question. The aim of this prospective, randomized comparative study was to investigate the efficacies of 14-day hybrid therapy and bismuth quadruple therapy in the treatment of infection. From July 2013 to June 2015, eligible -infected subjects were randomly assigned to receive either 14-day bismuth quadruple therapy (pantoprazole, bismuth subcitrate, tetracycline, and metronidazole for 14 days) or 14-day hybrid therapy (a 7-day dual therapy with pantoprazole plus amoxicillin, followed by a 7-day quadruple therapy with pantoprazole plus amoxicillin, clarithromycin, and metronidazole). status was examined 6 weeks after the end of treatment. Three hundred thirty -infected participants were randomized to receive 14-day bismuth quadruple therapy ( = 164) or 14-day hybrid therapy ( = 166). The eradication rates by intention-to-treat analysis were similar: 93.9% versus 92.8%, respectively (95% confidence interval [CI], -4.3% to 5.4%; = 0.68). Per-protocol analysis yielded similar results (96.7% versus 94.9%, respectively; = 0.44). However, bismuth quadruple therapy had a higher frequency of adverse events than hybrid therapy (55.5% versus 15.7%, respectively; 95% CI, 30.4% to 49.2%; < 0.001). The two treatments exhibited comparable drug adherence (93.9% versus 97%, respectively). The resistance rates of antibiotics were: clarithromycin, 16.7% of patients; amoxicillin, 1.3%; metronidazole, 25%; and tetracycline, 0%. In the bismuth quadruple therapy group, the eradication rate of metronidazole-resistant strains was lower than that of metronidazole-susceptible strains (70.0% versus 96.4%, respectively; = 0.04). In the hybrid therapy group, no significant impact of clarithromycin or metronidazole resistance on eradication rates was identified. Both 14-day hybrid and bismuth quadruple therapies cure most patients with infection in populations with moderate antibiotic resistance. However, the 14-day hybrid therapy has fewer adverse effects than the bismuth quadruple therapy. (This study has been registered at ClinicalTrials.gov under identifier NCT02541864.).

Trend of changes in antibiotic resistance in Helicobacter pylori from 2013 to 2019: a multicentre report from Taiwan

“…[21][22][23] Alternatively, bismuth or non-bismuth-containing quadruple therapy, high-dose PPI dual therapy, and hybrid therapy can attain >90% success as first-line H. pylori eradication regimens in both areas with high (>15%) and low (<15%) clarithromycin resistance. 5,6,22,[24][25][26] Recent studies reported the emergence of a novel potassium-competitive acid blocker (vonoprazan) that provides a stronger and longer-lasting effect on gastric acid suppression than other PPIs. 27 Vonoprazan-containing dual therapy (vonoprazan 20 mg + amoxicillin 750 mg twice per day) achieved a higher eradication rate than vonoprazan-containing triple therapy against clarithromycin-resistant strains (92.3% versus 76.2%; p = 0.048).…”

Helicobacter pylori eradication with bismuth quadruple therapy leads to dysbiosis of gut microbiota with an increased relative abundance of Proteobacteria and decreased relative abundances of Bacteroidetes and Actinobacteria

“…Helicobacter pylori ‐infected adult patients (age >20 years) with gastritis are documented by esophagogastroduodenoscopy in the Kaohsiung Veterans General Hospital. H pylori infection was confirmed by at least two positive results of rapid urease test, histology, and culture . Subjects with any of the following criteria were excluded from this trial: (1) previous eradication therapy, (2) allergy to any antibiotic of our study, (3) previous gastrectomy, (4) the coexistence of severe concomitant illness, (5) pregnancy or lactation women, (6) the use of antibiotics within the previous 8 weeks, and (7) taking proton pump inhibitor or histamine‐2 receptor antagonist within previous 8 weeks.…”

“…H pylori infection was confirmed by at least two positive results of rapid urease test, histology, and culture. 20 Subjects with any of the following criteria were excluded from this trial: (1) previous eradication therapy, (2) allergy to any antibiotic of our study, (3) previous gastrectomy, (4) the coexistence of severe concomitant illness, (5) pregnancy or lactation women, (6) the use of antibiotics within the previous 8 weeks, and (7) taking proton pump inhibitor or histamine-2 receptor antagonist within previous 8 weeks. This trial was approved by the Institutional Review Board of the Kaohsiung Veterans General Hospital (VGHKS15-CT2-10).…”

“…In the recent American College of Gastroenterology (ACG) guideline, it is recommended as a first‐line treatment for H. pylori infection . However, the therapy is associated with a high frequency of adverse events . Currently, the impact of bismuth quadruple therapy on the gut microbiota remains unknown, and whether the development of side effects is due to perturbation of gut microbiota is unclear.…”

“…17 However, the therapy is associated with a high frequency of adverse events. [18][19][20] Currently, the impact of bismuth quadruple therapy on the gut microbiota remains unknown, and whether the development of side effects is due to perturbation of gut microbiota is unclear.…”