The second Irish Helicobacter pylori Working Group consensus for the diagnosis and treatment of Helicobacter pylori infection in adult patients in Ireland.

BACKGROUND: There has been an increase in resistance to many of the antimicrobials used to treat Helicobacter pylori (H. pylori) nationally and internationally. Primary clarithromycin resistance and dual clarithromycin and metronidazole resistance are high in Ireland. These trends call for an evaluation of best-practice management strategies. OBJECTIVE: The objective of this study was to revise the recommendations for the management of H. pylori infection in adult patients in the Irish healthcare setting. METHODS: The Irish H. pylori working group (IHPWG) was established in 2016 and reconvened in 2023 to evaluate the most up-to-date literature on H. pylori diagnosis, eradication rates and antimicrobial resistance. The 'GRADE' approach was then used to rate the quality of available evidence and grade the resulting recommendations. RESULTS: The Irish H. pylori working group agreed on 14 consensus statements. Key recommendations include (1) routine antimicrobial susceptibility testing to guide therapy is no longer recommended other than for clarithromycin susceptibility testing for first-line treatment (statements 6 and 9), (2) clarithromycin triple therapy should only be prescribed as first-line therapy in cases where clarithromycin susceptibility has been confirmed (statement 9), (3) bismuth quadruple therapy (proton pump inhibitor, bismuth, metronidazole, tetracycline) is the recommended first-line therapy if clarithromycin resistance is unknown or confirmed (statement 10), (4) bismuth quadruple therapy with a proton pump inhibitor, levofloxacin and amoxicillin is the recommended second-line treatment (statement 11) and (5) rifabutin amoxicillin triple therapy is the recommend rescue therapy (statement 12). CONCLUSION: These recommendations are intended to provide the most relevant current best-practice guidelines for the management of H. pylori infection in adults in Ireland.

Helicobacter pylori: High dose amoxicillin does not improve primary or secondary eradication rates in an Irish cohort.

BACKGROUND: Helicobacter pylori (H. pylori) eradication rates have fallen globally, likely in large part due to increasing antibiotic resistance to traditional therapy. In areas of high clarithromycin and metronidazole resistance such as ours, Maastricht VI guidelines suggest high dose amoxicillin dual therapy (HDADT) can be considered, subject to evidence for local efficacy. In this study we assess efficacy of HDADT therapy for H. pylori eradication in an Irish cohort. AIM: To assess the efficacy of HDADT therapy for H. pylori eradication in an Irish cohort as both first line, and subsequent therapy for patients diagnosed with H. pylori. METHODS: All patients testing positive for H. pylori in a tertiary centre were treated prospectively with HDADT (amoxicillin 1 g tid and esomeprazole 40 mg bid × 14 d) over a period of 8 months. Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy. A delta-over-baseline > 4% was considered positive. Patient demographics and treatment outcomes were recorded, analysed and controlled for basic demographics and prior H. pylori treatment. RESULTS: One hundred and ninety-eight patients were identified with H. pylori infection, 10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing. In all 139 were included in the analysis, 55% (n = 76) were female, mean age was 46.6 years. Overall, 93 (67%) of patients were treatment-naïve and 46 (33%) had received at least one previous course of treatment. The groups were statistically similar. Self-reported compliance with HDADT was 97%, mild side-effects occurred in 7%. There were no serious adverse drug reactions. Overall the eradication rate for our cohort was 56% (78/139). Eradication rates were worse for those with previous treatment [43% (20/46) vs 62% (58/93), P = 0.0458, odds ratio = 2.15]. Age and Gender had no effect on eradication status. CONCLUSION: Overall eradication rates with HDADT were disappointing. Despite being a simple and possibly better tolerated regime, these results do not support its routine use in a high dual resistance country. Further investigation of other regimens to achieve the > 90% eradication target is needed.

Role of compliance in Helicobacter pylori eradication treatment: Results of the European Registry on H. pylori management.

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.

Comparison of the management of Helicobacter pylori infection between the older and younger European populations.

The prevalence of Helicobacter pylori remains high in the older population. Specific age-related peculiarities may impact the outcomes of H. pylori treatment. The aim of the study was to evaluate the diagnostics and effectiveness of H. pylori eradication between the younger and older European populations. "European Registry on H. pylori Management (Hp-EuReg)" data from 2013 to 2022 were analyzed. Patients were divided into older (≥ 60 years) and younger (18-59 years) groups. Modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. 49,461 patients included of which 14,467 (29%) were older-aged. Concomitant medications and penicillin allergy were more frequent among the older patients. Differences between younger and older populations were observed in treatment duration in first-line treatment and in proton pump inhibitors (PPIs) doses in second-line treatment. The overall incidence of adverse events was lower in the older adults group. The overall first-line treatment mITT effectiveness was 88% in younger and 90% in the older patients (p < 0.05). The overall second-line mITT treatment effectiveness was 84% in both groups. The effectiveness of the most frequent first- and second-line triple therapies was suboptimal (< 90%) in both groups. Optimal efficacy (≥ 90%) was achieved by using bismuth and non-bismuth-based quadruple therapies. In conclusion, the approach to the diagnostics and treatment of H. pylori infection did not generally differ between younger and older patients. Main differences were reported in the concurrent medications, allergy to penicillin and adverse events both in first- and second-line treatment. Optimal effectiveness rates were mostly achieved by using bismuth and non-bismuth-based quadruple therapies. No clinically relevant differences in the effectiveness between the age groups were observed.

Analysis of Clinical Phenotypes through Machine Learning of First-Line H. pylori Treatment in Europe during the Period 2013-2022: Data from the European Registry on H. pylori Management (Hp-EuReg).

The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the "most important" variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013-2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin-clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth-quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin-amoxicillin-metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year.

Strategies for the Purification of Membrane Proteins.

Membrane proteins account for approximately 30% of the coding regions of all sequenced genomes, and they play crucial roles in many fundamental cell processes. However, there are relatively few membrane proteins with known three-dimensional structures. This is likely due to technical challenges associated with membrane protein extraction, solubilization, and purification. Membrane proteins are classified based on the level of interaction with membrane lipid bilayers, with peripheral membrane proteins associating non-covalently with the membrane, and integral membrane proteins associating more strongly by means of hydrophobic interactions. Generally speaking, peripheral membrane proteins can be purified by milder techniques than integral membrane proteins, with the latter's extraction requiring phospholipid bilayer disruption using detergents or organic solvents. In this chapter, important considerations for membrane protein purification are addressed, with a focus on the initial stages of membrane protein solubilization, where problems are most frequently encountered. Protocols are outlined for the extraction of peripheral membrane proteins, solubilization of integral membrane proteins, and sample clean-up and concentration.

Helicobacter pylori Diagnostic Tests Used in Europe: Results of over 34,000 Patients from the European Registry on Helicobacter pylori Management.

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.

Impact of test, vaccinate or remove protocol on home ranges and nightly movements of badgers a medium density population.

In the British Isles, the European badger (Meles meles) is thought to be the primary wildlife reservoir of bovine tuberculosis (bTB), an endemic disease in cattle. Test, vaccinate or remove ('TVR') of bTB test-positive badgers, has been suggested to be a potentially useful protocol to reduce bTB incidence in cattle. However, the practice of removing or culling badgers is controversial both for ethical reasons and because there is no consistent observed effect on bTB levels in cattle. While removing badgers reduces population density, it may also result in disruption of their social behaviour, increase their ranging, and lead to greater intra- and inter-species bTB transmission. This effect has been recorded in high badger density areas, such as in southwest England. However, little is known about how TVR affects the behaviour and movement of badgers within a medium density population, such as those that occur in Northern Ireland (NI), which the current study aimed to examine. During 2014-2017, badger ranging behaviours were examined prior to and during a TVR protocol in NI. Nightly distances travelled by 38 individuals were determined using Global Positioning System (GPS) measurements of animal tracks and GPS-enhanced dead-reckoned tracks. The latter was calculated using GPS, tri-axial accelerometer and tri-axial magnetometer data loggers attached to animals. Home range and core home range size were measured using 95% and 50% autocorrelated kernel density estimates, respectively, based on location fixes. TVR was not associated with measured increases in either distances travelled per night (mean = 3.31 ± 2.64 km) or home range size (95% mean = 1.56 ± 0.62 km2, 50% mean = 0.39 ± 0.62 km2) over the four years of study. However, following trapping, mean distances travelled per night increased by up to 44% eight days post capture. Findings differ from those observed in higher density badger populations in England, in which badger ranging increased following culling. Whilst we did not assess behaviours of individual badgers, possible reasons why no differences in home range size were observed include higher inherent 'social fluidity' in Irish populations whereby movements are less restricted by habitat saturation and/or that the numbers removed did not reach a threshold that might induce increases in ranging behaviour. Nevertheless, short-term behavioural disruption from trapping was observed, which led to significant increases in the movements of individual animals within their home range. Whether or not TVR may alter badger behaviours remains to be seen, but it would be better to utilise solutions such as oral vaccination of badgers and/or cattle as well as increased biosecurity to limit bTB transmission, which may be less likely to cause interference and thereby reduce the likelihood of bTB transmission.

The double-edged sword of probiotic supplementation on gut microbiota structure in Helicobacter pylori management.

As Helicobacter pylori management has become more challenging and less efficient over the last decade, the interest in innovative interventions is growing by the day. Probiotic co-supplementation to antibiotic therapies is reported in several studies, presenting a moderate reduction in drug-related side effects and a promotion in positive treatment outcomes. However, the significance of gut microbiota involvement in the competence of probiotic co-supplementation is emphasized by a few researchers, indicating the alteration in the host gastrointestinal microbiota following probiotic and drug uptake. Due to the lack of long-term follow-up studies to determine the efficiency of probiotic intervention in H. pylori eradication, and the delicate interaction of the gut microbiota with the host wellness, this review aims to discuss the gut microbiota alteration by probiotic co-supplementation in H. pylori management to predict the comprehensive effectiveness of probiotic oral administration.Abbreviations: acyl-CoA- acyl-coenzyme A; AMP- antimicrobial peptide; AMPK- AMP-activated protein kinase; AP-1- activator protein 1; BA- bile acid; BAR- bile acid receptor; BCAA- branched-chain amino acid; C2- acetate; C3- propionate; C4- butyrate; C5- valeric acid; CagA- Cytotoxin-associated gene A; cAMP- cyclic adenosine monophosphate; CD- Crohn's disease; CDI- C. difficile infection; COX-2- cyclooxygenase-2; DC- dendritic cell; EMT- epithelial-mesenchymal transition; FMO- flavin monooxygenases; FXR- farnesoid X receptor; GPBAR1- G-protein-coupled bile acid receptor 1; GPR4- G protein-coupled receptor 4; H2O2- hydrogen peroxide; HCC- hepatocellular carcinoma; HSC- hepatic stellate cell; IBD- inflammatory bowel disease; IBS- irritable bowel syndrome; IFN-γ- interferon-gamma; IgA immunoglobulin A; IL- interleukin; iNOS- induced nitric oxide synthase; JAK1- janus kinase 1; JAM-A- junctional adhesion molecule A; LAB- lactic acid bacteria; LPS- lipopolysaccharide; MALT- mucosa-associated lymphoid tissue; MAMP- microbe-associated molecular pattern; MCP-1- monocyte chemoattractant protein-1; MDR- multiple drug resistance; mTOR- mammalian target of rapamycin; MUC- mucin; NAFLD- nonalcoholic fatty liver disease; NF-κB- nuclear factor kappa B; NK- natural killer; NLRP3- NLR family pyrin domain containing 3; NOC- N-nitroso compounds; NOD- nucleotide-binding oligomerization domain; PICRUSt- phylogenetic investigation of communities by reconstruction of unobserved states; PRR- pattern recognition receptor; RA- retinoic acid; RNS- reactive nitrogen species; ROS- reactive oxygen species; rRNA- ribosomal RNA; SCFA- short-chain fatty acids; SDR- single drug resistance; SIgA- secretory immunoglobulin A; STAT3- signal transducer and activator of transcription 3; T1D- type 1 diabetes; T2D- type 2 diabetes; Th17- T helper 17; TLR- toll-like receptor; TMAO- trimethylamine N-oxide; TML- trimethyllysine; TNF-α- tumor necrosis factor-alpha; Tr1- type 1 regulatory T cell; Treg- regulatory T cell; UC- ulcerative colitis; VacA- Vacuolating toxin A.

Chemical Composition and In Vitro Anti-Helicobacter pylori Activity of Campomanesia lineatifolia Ruiz & Pavón (Myrtaceae) Essential Oil.

Helicobacter pylori is the most common cause of gastritis and peptic ulcers, and the number of resistant strains to multiple conventional antimicrobial agents has been increasing in different parts of the world. Several studies have shown that some essential oils (EO) have bioactive compounds, which can be attributed to antimicrobial activity. Therefore, EOs have been proposed as a natural alternative to antibiotics, or for use in combination with conventional treatment for H. pylori infection. Campomanesia lineatifolia is an edible species found in the Brazilian forests, and their leaves are traditionally used for the treatment of gastrointestinal disorders. Anti-inflammatory, gastroprotective, and antioxidant properties are attributed to C. lineatifolia leaf extracts; however, studies related to the chemical constituents of the essential oil and anti-H. pylori activity is not described. This work aims to identify the chemical composition of the EO from C. lineatifolia leaves and evaluate the anti-H. pylori activity. The EO was obtained by hydrodistillation from C. lineatifolia leaves and characterized by gas chromatography-mass spectrometry analyses. To assess the in vitro anti-H. pylori activity of the C. lineatifolia leaf's EO (6 µL/mL-25 µL/mL), we performed broth microdilution assays by using type cultures (ATCC 49503, NCTC 11638, both clarithromycin-sensitive) and clinical isolate strains (SSR359, clarithromycin-sensitive, and SSR366, clarithromycin-resistant). A total of eight new compounds were identified from the EO (3-hexen-1-ol (46.15%), α-cadinol (20.35%), 1,1-diethoxyethane (13.08%), 2,3-dicyano-7,7-dimethyl-5,6-benzonorbornadiene (10.78%), aromadendrene 2 (3.0%), [3-S-(3α, 3aα, 6α, 8aα)]-4,5,6,7,8,8a-hexahydro-3,7,7-trimethyl-8-methylene-3H-3a,6-methanoazulene (2.99%), α-bisabolol (0.94%), and ß-curcumene (0.8%)), corresponding to 98.09% of the total oil composition. The EO inhibited the growth of all H. pylori strains tested (MIC 6 µL/mL). To our knowledge, the current study investigates the relation between the chemical composition and the anti-H. pylori activity of the C. lineatifolia EO for the first time. Our findings show the potential use of the C. lineatifolia leaf EO against sensitive and resistant clarithromycin H. pylori strains and suggest that this antimicrobial activity could be related to its ethnopharmacological use.

Experience with Rifabutin-Containing Therapy in 500 Patients from the European Registry on Helicobacter pylori Management (Hp-EuReg).

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.

Combined antrum and corpus biopsy protocol improves Helicobacter pylori culture success.

BACKGROUND: Helicobacter pylori (H. pylori) causes chronic gastritis, peptic ulcer disease, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Eradication rates have fallen, mainly due to antimicrobial resistance. Consensus guidelines recommend that first-line treatment is based on the local prevalence of antimicrobial resistance and that rescue therapies are guided by antimicrobial susceptibility testing (AST). However, H. pylori culture is challenging and culture-based AST is not routinely performed in the majority of hospitals. Optimisation of H. pylori culture from clinical specimens will enable more widespread AST to determine the most appropriate antimicrobials for H. pylori eradication. AIM: To determine whether dual antrum and corpus biopsy sampling is superior to single antrum biopsy sampling for H. pylori culture. METHODS: The study received ethical approval from the joint research ethics committee of Tallaght University Hospital and St. James's Hospital. Patients referred for upper gastrointestinal endoscopy were invited to participate. Biopsies were collected in tubes containing Dent's transport medium and patient demographics were recorded. Biopsies were used to inoculate Colombia blood agar plates. Plates were incubated under microaerobic conditions and evaluated for the presence of H. pylori. Statistical analyses were performed using Graphpad PRISM. Continuous variables were compared using the two-tailed independent t-test. Categorical variables were compared using the two-tailed Fisher exact test. In all cases, a P value less than 0.05 was considered significant. RESULTS: In all, samples from 219 H. pylori-infected patients were analysed in the study. The mean age of recruited patients was 48 ± 14.9 years and 50.7% (n = 111) were male. The most common endoscopic finding was gastritis (58.9%; n = 129). Gastric ulcer was diagnosed in 4.6% (n = 10) of patients, while duodenal ulcer was diagnosed in 2.7% (n = 6). Single antrum biopsies were collected from 73 patients, whereas combined antrum and corpus biopsies were collected from 146 patients. There was no significant difference in age, sex or endoscopic findings between the two groups. H. pylori was successfully cultured in a significantly higher number of cases when combined antrum and corpus biopsies were used compared to a single antrum biopsy [64.4% (n = 94/146) vs 49.3% (36/73); P = 0.04)]. CONCLUSION: Combined corpus and antrum biopsy sampling improves H. pylori culture success compared to single antrum biopsy sampling.

Empirical Second-Line Therapy in 5000 Patients of the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND & AIMS: After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe. METHODS: This international, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality. RESULTS: Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization. CONCLUSIONS: Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131.

Empirical rescue treatment of Helicobacter pylori infection in third and subsequent lines: 8-year experience in 2144 patients from the European Registry on H. pylori management (Hp-EuReg).

OBJECTIVE: To evaluate the use, effectiveness and safety of Helicobacter pylori empirical rescue therapy in third and subsequent treatment lines in Europe. DESIGN: International, prospective, non-interventional registry of the clinical practice of European gastroenterologists. Data were collected and quality reviewed until October 2021 at Asociación Española de Gastroenterología-Research Electronic Data Capture. All cases with three or more empirical eradication attempts were assessed for effectiveness by modified intention-to-treat and per-protocol analysis. RESULTS: Overall, 2144 treatments were included: 1519, 439, 145 and 41 cases from third, fourth, fifth and sixth treatment lines, respectively. Sixty different therapies were used; the 15 most frequently prescribed encompassed >90% of cases. Overall effectiveness remained <90% in all therapies. Optimised treatments achieved a higher eradication rate than non-optimised (78% vs 67%, p<0.0001). From 2017 to 2021, only 44% of treatments other than 10-day single-capsule therapy used high proton-pump inhibitor doses and lasted ≥14 days. Quadruple therapy containing metronidazole, tetracycline and bismuth achieved optimal eradication rates only when prescribed as third-line treatment, either as 10-day single-capsule therapy (87%) or as 14-day traditional therapy with tetracycline hydrochloride (95%). Triple amoxicillin-levofloxacin therapy achieved 90% effectiveness in Eastern Europe only or when optimised. The overall incidence of adverse events was 31%. CONCLUSION: Empirical rescue treatment in third and subsequent lines achieved suboptimal effectiveness in most European regions. Only quadruple bismuth-metronidazole-tetracycline (10-day single-capsule or 14-day traditional scheme) and triple amoxicillin-levofloxacin therapies reached acceptable outcomes in some settings. Compliance with empirical therapy optimisation principles is still poor 5 years after clinical practice guidelines update. TRIAL REGISTRATION NUMBER: NCT02328131.

Antibiotic Resistance Prevalence and Trends in Patients Infected with Helicobacter pylori in the Period 2013-2020: Results of the European Registry on H. pylori Management (Hp-EuReg).

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.

Molecular Detection of Antibiotic-Resistant Helicobacter pylori.

Antimicrobial susceptibility testing (AST) for H. pylori is essential to accurately assess the prevalence of antibiotic resistance in each population. Antibiotic resistance rates form the basis of local guidelines for H. pylori treatment and AST may also be used as a personalized medicine approach to tailor therapy. This chapter provides an update on global antibiotic resistance rates and describes molecular mechanisms that confer H. pylori antibiotic resistance. An overview on the advantages and limitations of molecular AST using both invasive and noninvasive approaches is also provided.

An Overview of Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) represents one of the most widespread bacterial infections globally. Infection causes chronic gastritis and increases the risk of peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. The pioneering discovery of H. pylori by Marshall and Warren in the early 1980s has initiated fervent research into H. pylori as a pathogen ever since. This chapter aims to provide an overview of our understanding of H. pylori infection and its management, with a focus on current options for diagnosis, the challenges associated with H. pylori eradication, and the need for alternative therapeutic strategies based on furthering our understanding of host: H. pylori interactions.