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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 leukope nia 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.

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. &ldquo, Optimized&rdquo, H. pylori therapies achieve over 90% success in Spain.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Background: There has been resurgence in the use of bismuth quadruple therapy (proton pump inhibitor, bismuth, tetracycline and metronidazole) for treating Helicobacter pylori infection thanks to a three-in-one single-capsule formulation. Objective: To evaluate the effectiveness and safety of the single-capsule bismuth quadruple therapy. Methods: Data were collected in a multicentre, prospective registry of the clinical practice of gastroenterologists on the management of H. pylori infection, where patients were registered at the Asociación Española de Gastroenterologia REDCap database on an electronic case report form until January 2020. Effectiveness by modified intention-to-treat and per-protocol as well as multivariable analysis were performed. Independent factors evaluated were: age, gender, indication, compliance, proton pump inhibitor dose and treatment line. Results: Finally, 2100 patients were prescribed single-capsule bismuth quadruple therapy following the technical sheet (i.e., three capsules every 6 h for 10 days). The majority of these patients were naive (64%), with an average age of 50 years, 64% women and 16% with peptic ulcer. An overall modified intention-to-treat effectiveness of 92% was achieved. Eradication was over 90% in first-line treatment (95% modified intention-to-treat, n = 1166), and this was maintained as a rescue therapy, both in second (89% modified intention-to-treat, n = 375) and subsequent lines of therapy (third to sixth line: 92% modified intention-to-treat, n = 236). Compliance was the factor most closely associated with treatment effectiveness. Adverse events were generally mild to moderate, and 3% of patients reported a severe adverse event, leading to discontinuation of treatment in 1.7% of cases. Conclusions: Single-capsule bismuth quadruple therapy achieved H. pylori eradication in approximately 90% of patients in real-world clinical practice, both as a first-line and rescue treatment, with good compliance and a favourable safety profile, The author(s) would like to thank the Spanish Association of Gastroenterology (AEG) for providing the electronic case report form service free of charge. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was promoted and funded by the European Helicobacterand Microbiota Study Group, and received support from the Spanish Association of Gastroenterology (AEG) and the Centro de Investigación Biomedica en Red de Enfermedades Hepaticas y Digestivas

The multicenter prospective observational study initiated by the European Helicobacter and Microbiota Study Group (EHMSG) is conducted in 27 countries in Europe. The data from the Russian part of the European registry for the management of Helicobacter pylori infection (European Registry on the management of Helicobacter pylori infection, protocol: "Hp-EuReg") allows us to analyze the real clinical practice of diagnosis and treatment of H. pylori and compare it with international recommendations.A comparative analysis of the data entered in the register by the Russian research centers "Hp-EuReg", in the period from 2013 to 2018, was conducted.Invasive diagnostic methods prevail for the primary diagnosis of H. pylori [histology - 20.3% (in 2013 year) - 43.9% (in 2018 year), rapid urease test - 31.7% and 47.8% respectively]. The most popular mode of eradication therapy is a 10-day triple therapy (62.8-76.2%), the effectiveness of which does not exceed 79% (per protocol). Invasive tests (histology) are the leading method for control the effectiveness of therapy, however, there is a tendency towards a wider use of non-invasive methods (H. pylori stool antigen - from 17% in 2013 to 29.3% in 2018 and urea breath test from 6.9 to 18.3%, respectively). Serological test to control the effectiveness of eradication is still used from 8.2% (2013) to 6.1% (2018). Eradication therapy was not performed in 28% of patients throughout the entire observation period.In Russia, despite approved domestic and international recommendations, deviations in clinical practice persist, both during eradication therapy and in monitoring the effectiveness of eradication therapy.от имени научного комитета и исследователей Hp-EuReg Наблюдательное многоцентровое проспективное исследование, инициированное Европейской группой по изучению Helicobacter pylori и микробиоты (EHMSG), проводится в 27 странах Европы. Данные российской части Европейского регистра ведения инфекции Helicobacter pylori (European Registry on the management of Helicobacter pylori infection, протокол: «Hp-EuReg») позволяют проанализировать реальную клиническую практику диагностики и лечения H. pylori и сопоставить ее с международными рекомендациями. Материалы и методы. Проведен сравнительный анализ данных, внесенных в регистр российскими центрами исследования «Hp-EuReg» в период с 2013 г. по февраль 2018 г. Результаты и обсуждение. Для первичной диагностики H. pylori доминируют инвазивные методы: гистологическое исследование (20,3% в 2013 г. и 43,9% в 2018 г.) и быстрый уреазный тест (31,7 и 47,8% соответственно). Наиболее часто назначаемым режимом эрадикации является 10-дневная тройная терапия (62,8-76,2%), эффективность которой per protocol не превышает 79%. Ведущим методом контроля эффективности остаются инвазивные тесты (гистологическое исследование), однако намечается тенденция к росту применения неинвазивных методов: моноклонального теста на антиген H. pylori в кале (с 17% в 2013 г. до 29,3% в 2018 г.) и уреазного дыхательного теста (с 6,9 до 18,3% соответственно). Серологический тест с целью контроля эрадикации продолжают использовать от 8,2% в 2013 г. до 6,1% в 2018 г. Не проводился контроль у 28% больных. Выводы. В России сохраняются значимые отклонения клинической практики от отечественных и международных рекомендаций, как при проведении эрадикационной терапии, так и на этапе контроля ее эффективности.

Supplemental material, sj-pdf-1-ueg-10.1177_2050640620972615 for European Registry on Helicobacter pylori Management: single-capsule bismuth quadruple therapy is effective in real-world clinical practice by Olga P Nyssen, Angeles Perez-Aisa, Manuel Castro-Fernandez, Rinaldo Pellicano, Jose M. Huguet, Luis Rodrigo, Juan Ortuño, Blas Jose Gomez-Rodriguez, Ricardo Marcos Pinto, Miguel Areia, Monica Perona, Oscar Nuñez, Marco Romano, Antonietta Gerarda Gravina, Liliana Pozzati, Miguel Fernandez-Bermejo, Marino Venerito, Peter Malfertheiner, Luis Fernanadez-Salazar, Antonio Gasbarrini, Dino Vaira, Ignasi Puig, Francis Megraud, Colm O’Morain and Javier P Gisbert in United European Gastroenterology Journal

Supplemental material, sj-pdf-2-ueg-10.1177_2050640620972615 for European Registry on Helicobacter pylori Management: single-capsule bismuth quadruple therapy is effective in real-world clinical practice by Olga P Nyssen, Angeles Perez-Aisa, Manuel Castro-Fernandez, Rinaldo Pellicano, Jose M. Huguet, Luis Rodrigo, Juan Ortuño, Blas Jose Gomez-Rodriguez, Ricardo Marcos Pinto, Miguel Areia, Monica Perona, Oscar Nuñez, Marco Romano, Antonietta Gerarda Gravina, Liliana Pozzati, Miguel Fernandez-Bermejo, Marino Venerito, Peter Malfertheiner, Luis Fernanadez-Salazar, Antonio Gasbarrini, Dino Vaira, Ignasi Puig, Francis Megraud, Colm O’Morain and Javier P Gisbert in United European Gastroenterology Journal

Background Non-bismuth quadruple sequential therapy (SEQ) comprising a first induction phase with a dual regimen of amoxicillin and a proton pump inhibitor (PPI) for five days followed by a triple regimen phase with a PPI, clarithromycin and metronidazole for another five days, has been suggested as a new first-line treatment option to replace the standard triple therapy (STT) comprising a proton pump inhibitor (PPI), clarithromycin and amoxicillin, in which eradication proportions have declined to disappointing levels. Objectives To conduct a meta-analysis of randomised controlled trials (RCTs) comparing the efficacy of a SEQ regimen with STT for the eradication of H. pylori infection, and to compare the incidence of adverse effects associated with both STT and SEQ H. pylori eradication therapies. Search methods We conducted bibliographical searches in electronic databases, and handsearched abstracts from Congresses up to April 2015. Selection criteria We sought randomised controlled trials (RCTs) comparing 10-day SEQ and STT (of at least seven days) for the eradication of H. pylori. Participants were adults and children diagnosed as positive for H. pylori infection and naive to H. pylori treatment. Data collection and analysis We used a pre-piloted, tabular summary to collect demographic and medical information of included study participants as well as therapeutic data and information related to the diagnosis and confirmatory tests. We evaluated the difference in intention-to-treat eradication between SEQ and STT regimens across studies, and assessed sources of the heterogeneity of this risk difference (RD) using subgroup analyses. We evaluated the quality of the evidence following Cochrane standards, and summarised it using GRADE methodology. Main results We included 44 RCTs with a total of 12,284 participants (6042 in SEQ and 6242 in STT). The overall analysis showed that SEQ was significantly more effective than STT (82% vs 75% in the intention-to-treat analysis; RD 0.09, 95% confidence interval (CI) 0.06 to 0.11; P < 0.001, moderate-quality evidence). Results were highly heterogeneous (I² = 75%), and 20 studies did not demonstrate differences between therapies. Reporting by geographic region (RD 0.09, 95% CI 0.06 to 0.12; studies = 44; I² = 75%, based on low-quality evidence) showed that differences between SEQ and STT were greater in Europe (RD 0.16, 95% CI 0.14 to 0.19) when compared to Asia, Africa or South America. European studies also showed a tendency towards better efficacy with SEQ; however, this tendency was reversed in 33% of the Asian studies. Africa reported the closest risk difference (RD 0.14 , 95% 0.07 to 0.22) to Europe among studied regions, but confidence intervals were wider and therefore the quality of the evidence showing SEQ to be superior to STT was reduced for this region. Based on high-quality evidence, subgroup analyses showed that SEQ and STT therapies were equivalent when STT lasted for 14 days. Although, overall, the mean eradication proportion with SEQ was over 80%, we noted a tendency towards a lower average effect with this regimen in the more recent studies (2008 and after); weighted linear regression showed that the efficacies of both regimens evolved differently over the years, having a higher reduction in the efficacy of SEQ (-1.72% yearly) than in STT (-0.9% yearly). In these more recent studies (2008 and after) we were also unable to detect the superiority of SEQ over STT when STT was given for 10 days. Based on very low-quality evidence, subgroup analyses on antibiotic resistance showed that the widest difference in efficacy between SEQ and STT was in the subgroup analysis based on clarithromycin-resistant participants, in which SEQ reached a 75% average efficacy versus 43% with STT. Reporting on adverse events (AEs) (RD 0.00, 95% CI -0.02 to 0.02; participants = 8103; studies = 27; I² = 26%, based on high-quality evidence) showed no significant differences between SEQ and STT (20.4% vs 19.5%, respectively) and results were homogeneous. The quality of the studies was limited due to a lack of systematic reporting of the factors affecting risk of bias. Although randomisation was reported, its methodology (e.g. algorithms, number of blocks) was not specified in several studies. Additionally, the other 'Risk of bias' domains (such as allocation concealment of the sequence randomisation, or blinding during either performance or outcome assessment) were also unreported. However, subgroup analyses as well as sensitivity analyses or funnel plots indicated that treatment outcomes were not influenced by the quality of the included studies. On the other hand, we rated 'length of STT' and AEs for the main outcome as high-quality according to GRADE classification; but we downgraded 'publication date' quality to moderate, and 'geographic region' and 'antibiotic resistance' to low- and very low-quality, respectively. Authors' conclusions Our meta-analysis indicates that prior to 2008 SEQ was more effective than STT, especially when STT was given for only seven days. Nevertheless, the apparent advantage of sequential treatment has decreased over time, and more recent studies do not show SEQ to have a higher efficacy versus STT when STT is given for 10 days. Based on the results of this meta-analysis, although SEQ offers an advantage when compared with STT, it cannot be presented as a valid alternative, given that neither SEQ nor STT regimens achieved optimal efficacy ( ≥ 90% eradication rate).