Background: Bacterial antibiotic resistance changes over time depending on multiple factors; therefore, it is essential to monitor the susceptibility trends to reduce the resistance impact on the effectiveness of various treatments. Objective: To conduct a time-trend analysis of Helicobacter pylori resistance to antibiotics in Europe. Methods: The international prospective European Registry on Helicobacter pylori Management (Hp-EuReg) collected data on all infected adult patients diagnosed with culture and antimicrobial susceptibility testing positive results that were registered at AEG-REDCap e-CRF until December 2020. Results: Overall, 41,562 patients were included in the Hp-EuReg. Culture and antimicrobial susceptibility testing were performed on gastric biopsies of 3974 (9.5%) patients, of whom 2852 (7%) were naive cases included for analysis. The number of positive cultures decreased by 35% from the period 2013–2016 to 2017–2020. Concerning naïve patients, no antibiotic resistance was found in 48% of the cases. The most frequent resistances were reported against metronidazole (30%), clarithromycin (25%), and levofloxacin (20%), whereas resistances to tetracycline and amoxicillin were below 1%. Dual and triple resistances were found in 13% and 6% of the cases, respectively. A decrease (p < 0.001) in the metronidazole resistance rate was observed between the 2013–2016 (33%) and 2017–2020 (24%) periods. Conclusion: Culture and antimicrobial susceptibility testing for Helicobacter pylori are scarcely performed (<10%) in Europe. In naïve patients, Helicobacter pylori resistance to clarithromycin remained above 15% throughout the period 2013–2020 and resistance to levofloxacin, as well as dual or triple resistances, were high. A progressive decrease in metronidazole resistance was observed.

Background: Bismuth‐containing quadruple therapy has been suggested as first‐line and rescue alternative for Helicobacter pylori eradication. Our objective was to perform a meta‐analysis evaluating the efficacy and safety of single capsule Pylera^® (bismuth, metronidazole, and tetracycline) plus a proton‐pump inhibitor (PPI) in any line of treatment.Methods: Studies were selected up to October 2018. Outcomes were eradication and adverse events (AEs) rates pooled using the generic inverse variance method.Results: In total, 30 studies (6482 patients) were included in the systematic review. The intention‐to‐treat (ITT) efficacy was 90% (95% CI: 87%‐92%, 21 studies, I² = 88%) in first‐line therapy, 89% (95% CI: 86%‐93%, 12 studies, I² = 78%) in second‐line and 82% (95% CI: 78%‐87%, nine studies, I² = 60%) in third‐line; with no differences by the type or dosage of PPI used. For metronidazole‐resistant infection, the ITT efficacy as first‐line therapy was 93% (95% CI: 90%‐96%, six studies, I² = 0%). In second‐line therapies where patients had been previously treated with clarithromycin, the ITT efficacy was 90% (95% CI: 87%‐93%, 11 studies, I² = 78%). The overall incidence of AEs was 43% (95% CI: 35%‐50%, 24 studies, I² = 92%) and they were mostly mild. In nearly 3% of the cases, treatment was interrupted due to AEs.Conclusions: A 10‐day treatment with Pylera^® achieved an effective eradication rate of approximately 90% both in first‐ and second‐line therapy. This applies regardless of the type and dose of the PPI, in patients with clarithromycin‐ or metronidazole‐resistant strains, and in those previously treated with clarithromycin.

INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance. METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included. RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results. DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.

Background: Bismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of high bacterial antibiotic resistance. Objective: To describe the time trends of use, effectiveness and safety of BQT in Europe using the European Registry on Helicobacter pylori Management (Hp-EuReg). Design: Patients registered in the Hp-EuReg from 2013 to 2021 who had received BQT were included. The regimens prescribed, the number of eradication attempts, effectiveness, adherence and safety were analysed. The effectiveness was assessed by modified intention to treat (mITT). Time-trend and multivariate analyses were performed to determine variables that predicted treatment success. Results: Of the 49 690 patients included in the Hp-EuReg, 15 582 (31%) had received BQT. BQT use increased from 8.6% of all treatments in 2013 to 39% in 2021. Single-capsule BQT—containing bismuth, metronidazole and tetracycline—plus a PPI (single-capsule BQT, ScBQT) was the most frequent treatment mode (43%). Schemes that obtained an effectiveness above 90% were the 10-day ScBQT and 14-day BQT using tetracycline plus metronidazole, or amoxicillin plus either clarithromycin or metronidazole. Only ScBQT achieved above 90% cure rates in all the geographical areas studied. Using the ScBQT scheme, adherence, the use of standard or high-dose PPIs, 14-day prescriptions and the use of BQT as first-line treatment were significantly associated with higher mITT effectiveness. Conclusion: The use of BQT increased notably in Europe over the study period. A 10-day ScBQT was the scheme that most consistently achieved optimal effectiveness. Trial registration number: NCT02328131 .

Background: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy.Objective: To determine which factors influence compliance with treatment.Methods: A systematic prospective non‐interventional registry (Hp‐EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG‐REDCap e‐CRF and were subjected to quality control. Modified intention‐to‐treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance.Results: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non‐compliance rate was higher in patients prescribed longer regimens (10‐, 14‐days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non‐adherence was lower for first‐line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non‐adherence in the three most frequent first‐line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non‐compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2–7.7]; p < 0.001).Conclusions: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue‐treatment, prolonged treatment regimens, the presence of adverse events, and the use of non‐bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.

Background: Experience inHelicobacter pylorieradication treatment of patients allergic to penicillin is very scarce. A triple combination with a PPI, clarithromycin (C), and metronidazole (M) is often prescribed as the first option, although more recently the use of a quadruple therapy with PPI, bismuth (B), tetracycline (T), and M has been recommended.Aim: To evaluate the efficacy and safety of first‐line and rescue treatments in patients allergic to penicillin in the “European Registry ofH pylorimanagement” (Hp‐EuReg).Methods: A systematic prospective registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management ofH pyloriinfection. An e‐CRF was created on AEG‐REDCap. Patients with penicillin allergy were analyzed until June 2019.Results: One‐thousand eighty‐four patients allergic to penicillin were analyzed. The most frequently prescribed first‐line treatments were as follows: PPI + C + M (n = 285) and PPI + B + T + M (classic or Pylera^®; n = 250). In first line, the efficacy of PPI + C + M was 69%, while PPI + B + T + M reached 91% (P < .001). In second line, after the failure of PPI + C + M, two rescue options showed similar efficacy: PPI + B + T + M (78%) and PPI + C + levofloxacin (L) (71%) (P > .05). In third line, after the failure of PPI + C + M and PPI + C + L, PPI + B + T + M was successful in 75% of cases.Conclusion: In patients allergic to penicillin, a triple combination with PPI + C + M should not be generally recommended as a first‐line treatment, while a quadruple regimen with PPI + B + T + M seems to be a better option. As a rescue treatment, this quadruple regimen (if not previously prescribed) or a triple regimen with PPI + C + L could be used but achieved suboptimal (<80%) results.