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: First-line Helicobacter pylori (H. pylori) treatments have been relatively well evaluated; however, it remains necessary to identify the most effective rescue treatments. Our aim was to assess the effectiveness and safety of H. pylori regimens containing rifabutin. METHODS: International multicentre prospective non-interventional European Registry on H. pylori Management (Hp-EuReg). Patients treated with rifabutin were registered in AEG-REDCap e-CRF from 2013 to 2021. Modified intention-to-treat and per-protocol analyses were performed. Data were subject to quality control. Results: Overall, 500 patients included in the Hp-EuReg were treated with rifabutin (mean age 52 years, 72% female, 63% with dyspepsia, 4% with peptic ulcer). Culture was performed in 63% of cases: dual resistance (to both clarithromycin and metronidazole) was reported in 46% of the cases, and triple resistance (to clarithromycin, metronidazole, and levofloxacin) in 39%. In 87% of cases rifabutin was utilised as part of a triple therapy together with amoxicillin and a proton-pump-inhibitor, and in an additional 6% of the patients, bismuth was added to this triple regimen. Rifabutin was mainly used in second-line (32%), third-line (25%), and fourth-line (27%) regimens, achieving overall 78%, 80% and 66% effectiveness by modified intention-to-treat, respectively. Compliance with treatment was 89%. At least one adverse event was registered in 26% of the patients (most frequently nausea), and one serious adverse event (0.2%) was reported in one patient with leukopenia and thrombocytopenia with fever requiring hospitalisation. Conclusion: Rifabutin-containing therapy represents an effective and safe strategy after one or even several failures of H. pylori eradication treatment.

Background: Randomized clinical trials and meta-analyses, primarily from Asian countries, have reported good effectiveness with high-dose dual therapy (HDDT) including a proton pump inhibitor (PPI) and amoxicillin when prescribed as H. pylori first-line or rescue treatment. However, combining amoxicillin with PPIs in the 1990s in several European countries yielded suboptimal results. Methods: An international, multicenter, prospective non-interventional Registry (Hp-EuReg) aimed to evaluate the decisions and outcomes of H. pylori management by European gastroenterologists. All infected adult cases treated with HDDT were registered at e-CRF AEG-REDCap platform until June 2021. Sixty patients were prescribed with HDDT (98% compliance), 19 of them received a first-line therapy and 41 a rescue treatment (second- to sixth-line). Results: Overall HDDT effectiveness was 52% (per-protocol) and 51% (modified intention-to-treat). First-line and rescue treatment lines were equally effective, but the effectiveness was worse when patients had previously received metronidazole, tetracycline, or rifabutin. Adding bismuth to HDDT in rescue treatment did not yield better results. The incidence of adverse events was 30%, diarrhea being the most common (20% of patients); no serious adverse events were reported. Conclusion: Although HDDT is safe and has good compliance, it is not a good option in European first-line or rescue H. pylori treatment, even when adding bismuth.

The management of Helicobacter pylori infection has to rely on previous local effectiveness due to the geographical variability of antibiotic resistance. The aim of this study was to evaluate the effectiveness of first and second-line H. pylori treatment in Spain, where the empirical prescription is recommended. A multicentre prospective non-interventional registry of the clinical practice of European gastroenterologists concerning H. pylori infection (Hp-EuReg) was developed, including patients from 2013 until June 2019. Effectiveness was evaluated descriptively and through a multivariate analysis concerning age, gender, presence of ulcer, proton-pump inhibitor (PPI) dose, therapy duration and compliance. Overall, 53 Spanish hospitals were included, and 10,267 patients received a first-line therapy. The best results were obtained with the 10-day bismuth single-capsule therapy (95% cure rate by intention-to-treat) and with both the 14-day bismuth-clarithromycin quadruple (PPI-bismuth-clarithromycin-amoxicillin, 91%) and the 14-day non-bismuth quadruple concomitant (PPI-clarithromycin-amoxicillin-metronidazole, 92%) therapies. Second-line therapies were prescribed to 2448 patients, with most-effective therapies being the triple quinolone (PPI-amoxicillin-levofloxacin/moxifloxacin) and the bismuth-levofloxacin quadruple schemes (PPI-bismuth-levofloxacin-amoxicillin) prescribed for 14 days (92%, 89% and 90% effectiveness, respectively), and the bismuth single-capsule (10 days, 88.5%). Compliance, longer duration and higher acid inhibition were associated with higher effectiveness. “Optimized” H. pylori therapies achieve over 90% success in Spain.

Background and aims: Several methods are available to diagnose Helicobacter pylori infection. Our objective was to evaluate the tests used for both the initial diagnosis and the confirmation of eradication after treatment in Europe. Methods: The European Registry on the management of Helicobacter pylori infection is an international, multicentre, prospective, non-interventional registry aiming to evaluate the management of Helicobacter pylori-infected patients in Europe. Countries with at least 100 cases registered from June 2013 to April 2021, and with a validated diagnostic method were analysed. Data were quality reviewed. Results: A total of 34,920 adult patients from 20 countries were included (mean age 51 years; 61% women). To establish the initial diagnosis, invasive tests were performed in 19,801 (71%) patients, non-invasive in 11,369 (41%), and both in 3437 (12%). The most frequent were histology (n = 11,885; 43%), a rapid urease test (n = 10,636; 38%) and an urea breath test (n = 7577; 27%). According to the age, invasive tests were indicated in 11,179 (77%) ≥50 years, and in 8603 (65%) <50 years. Depending on the country, the use of invasive tests ranged from 29–99% in <50 years to 60–99% in ≥50. Most of the tests used to confirm eradication were non-invasive (n = 32,540; 93%), with the urea breath test being the most frequent (n = 32,540; 78%). In 2983 (9%) post-treatment tests, histology (n = 1887; 5%) or a rapid urease test (n = 1223; 4%) were performed. Conclusion: A great heterogeneity was observed for the initial diagnosis and confirmation of the eradication. The reasons for the apparent lack of adherence to the clinical guidelines should be further explored.