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.

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: Management of Helicobacter pylori (H. pylori) infection requires co‐treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication.Aim: To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the ‘European Registry on Helicobacter pylori management’ (Hp‐EuReg).Methods: Hp‐EuReg is a multicentre, prospective, non‐interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022.Results: Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first‐line‐modified intention‐to‐treat effectiveness was achieved with the following treatments: (1) 14‐day therapies with clarithromycin‐amoxicillin‐bismuth and metronidazole‐tetracycline‐bismuth, both independently of the PPI dose prescribed; (2) All 10‐day (except 10‐day standard triple therapy) and 14‐day therapies with high‐dose PPIs; and (3) 10‐day quadruple therapies with clarithromycin‐amoxicillin‐bismuth, metronidazole‐tetracycline‐bismuth, and clarithromycin‐amoxicillin‐metronidazole (sequential), all with standard‐dose PPIs. In first‐line treatment, optimal effectiveness was obtained with high‐dose PPIs in all 14‐day treatments, in 10‐ and 14‐day bismuth quadruple therapies and in 10‐day sequential with standard‐dose PPIs. Optimal second‐line effectiveness was achieved with (1) metronidazole‐tetracycline‐bismuth quadruple therapy for 14‐ and 10 days with standard and high‐dose PPIs, respectively; and (2) levofloxacin‐amoxicillin triple therapy for 14 days with high‐dose PPIs. None of the 7‐day therapies in both treatment lines achieved optimal effectiveness.Conclusions: We recommend, in first‐line treatment, the use of high‐dose PPIs in 14‐day triple therapy and in 10‐or 14‐day quadruple concomitant therapy in first‐line treatment, while standard‐dose PPIs would be sufficient in 10‐day bismuth quadruple therapies. On the other hand, in second‐line treatment, high‐dose PPIs would be more beneficial in 14‐day triple therapy with levofloxacin and amoxicillin or in 10‐day bismuth quadruple therapy either as a three‐in‐one single capsule or in the traditional scheme.

Background: Colorectal cancer (CRC) is one of the most common malignancies in the western world. Objective: We aimed to assess the first round of fecal immunochemical test (FIT)-based National CRC screening program (NCSP). Methods: In the NCSP conducted in Slovenia, a FIT and colonoscopy for those tested positive was used. The NCSP central unit sent 536,709 invitations to Slovenian residents age 50 to 69 years old between 2009 and 2011. The adherence rate was 56.9% (303,343 participants). FIT was positive in 6.2% (15,310) of the participants (men, 7.8%; women, 5.0%; P<0.01). A total of 13,919 unsedated colonoscopies were performed with the cecal intubation rate of 97.8%. Results: The overall adenoma detection rate was 51.3% [95% confidence interval (CI), 50.5%-52.1%] of which 61.0% (95% CI, 59.9%-62.1%) was in men, and 39.1% (95% CI, 37.8%-40.3%) in women (P<0.01). The mean number of adenoma per positive colonoscopy was 1.94 (95% CI, 1.90-1.97). Adenoma, advanced adenoma, or cancer were found in 7732 (55.5%) colonoscopies. A total of 862 (6.2%) CRC cases were found. Only 161 (18.7%) carcinomas were situated in the right colon. A total of 597 (70.2%) patients with cancer were in the early clinical stages (N, negative; 194 22.8%) of all cancers were cured with only endoscopic resection. Conclusions: In the NCSP, CRC was found in 6.2% of those participants attending colonoscopy, with 81.3% of carcinomas found in the left colon. A localized clinical stage was found in 70.2% participants. In 22.8% of CRC patients, cancer was cured with endoscopic resection only.