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Background: The influence of indications for Helicobacter pylori investigation on prescriptions and effectiveness is unknown. The aim of the study was to assess the impact of indications for H. pylori investigation on prescriptions, effectiveness, compliance, and tolerance., Methods: International, prospective, non-interventional registry of the management of H. pylori infection by European gastroenterologists (Hp-EuReg). Treatment-näive patients registered from 2013 to 2023 at e-CRF AEG-REDCap were analyzed. The effectiveness was assessed by modified intention-to-treat analysis., Results: Overall, 53,636 treatment-naïve cases from 34 countries were included. Most frequent indications were: dyspepsia with normal endoscopy (49%), non-investigated dyspepsia (20%), duodenal ulcer (11%), gastric ulcer (7.7%), and gastroesophageal reflux disease (GERD) (2.6%). Therapy effectiveness varied by indication: duodenal ulcer (91%), gastric ulcer (90%), preneoplastic lesions (90%), dyspepsia with normal endoscopy (89%), GERD (88%), and non-investigated dyspepsia (87%). Bismuth-metronidazole-tetracycline and clarithromycin-amoxicillin-bismuth quadruple therapies achieved 90% effectiveness in all indications except GERD. Concomitant clarithromycin-amoxicillin-tinidazole/metronidazole reached 90% cure rates except in patients with non-investigated dyspepsia; whereas sequential clarithromycin-amoxicillin-tinidazole/metronidazole proved optimal (≥90%) in patients with gastric ulcer only. Adverse events were higher in patients treated for dyspepsia with normal endoscopy and duodenal ulcer compared with the remaining indications (23% and 28%, p < 0.001). Therapeutic compliance was higher in patients with duodenal ulcer and preneoplastic lesions (98% and 99%, p < 0.001)., Conclusion: In Europe, patients with gastric or duodenal ulcers and preneoplastic lesions showed higher H. pylori treatment effectiveness. Bismuth and non-bismuth quadruple therapies achieved optimal results in almost all indications., Trial Registration: ClinicalTrials.gov identifier: NCT02328131., (© 2024 The Author(s). Helicobacter published by John Wiley & Sons Ltd.)

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., (Copyright © 2023 by The American College of Gastroenterology.)

Background and Aims: The optimal management of naïve and not naïve Helicobacter pylori patients remains unclear. Therefore, it is essential to evaluate whether the actual clinical practice mirrors the indications suggested by the guidelines. This study aimed to assess the effectiveness and the safety of the empirical first- and second-line treatments prescribed to patients enroled at Italian centres participating in the European Registry on H. pylori Management (Hp-EuReg)., Methods: The Hp-EuReg is an international multicentre prospective non-interventional registry starting in 2013 aiming to evaluate the management of H. pylori infection by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables assessed included demographics, previous eradication attempts, treatment regimen, effectiveness, and tolerance., Results: Overall, 3723 patients from 2013 to February 2021 were included: 2996 and 727 received an empirical first- and second-line treatment, respectively. According to the modified ITT analysis, among the first-line regimens, only the bismuth quadruple therapy with three-in-one-single capsule (BQT-TSC), the concomitant, and the sequential treatment - all lasting 10 days - achieved an eradication rate >90%. Among the second-line regimens, only the 10-day BQT-TSC reported an effectiveness >90%. High-dose PPI twice daily also significantly increased the effectiveness of some therapies. The BQT-TSC was the regimen with the highest incidence of adverse events., Conclusions: Only quadruple therapies lasting at least 10 days achieved over 90% eradication rates among the empirical first- and second-line regimens. It remains unclear whether high-dose PPI twice daily can improve the efficacy of quadruple treatment., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Materials and Methods: Consecutive foreigner patients with H. pylori infection following at least one therapy failure were enrolled. All patients underwent upper endoscopy with gastric biopsies used for both histologic examination and culture/susceptibility test. Rescue therapies administered accordingly to susceptibility testing were rifabutin-based therapy, levofloxacin-based therapy, sequential. Pylera was prescribed regardless the resistance pattern., Results: A total of 103 (M/F: 27/76, mean age: 41.9 y, range: 18 to 85) were enrolled. The overall resistance rates toward clarithromycin, metronidazole, and levofloxacin were 76.7%, 66%, and 42.7%, respectively, with triple resistance present in 33.9% of bacterial isolates. Eradication rates were 71.4% on 40 patients for rifabutin-based therapy, 82.8% on 42 cases for levofloxacin-based therapy, 75% on 11 patients treated with sequential therapy, and 100% on 10 cases who received Pylera regimen., Conclusions: To our knowledge, this is the first study assessing H. pylori eradication rates in foreigner patients, who failed at least one therapeutic attempt, managed in Italy. Even by using a culture-based approach, the infection was not cured in a definite number of patients., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Curing H. pylori infection remains challenging, and the use of most effective first-line therapy represents a therapeutic cornerstone. To monitor the efficacy of first-line therapies in Italy, we designed a systematic review with pooled- data analysis of data published in the last 15 years., Methods: The search was focused on standard regimens and adult patients. Studies that included modified therapy regimens, pediatric patients, case series with less than 5 patients, and those in language other than English were excluded., Results: A total of 40 studies, with 74 therapeutic arms and 13,539 patients were evaluated. Among the 14-day triple therapies, the combination with proton pump inhibitor (PPI), clarithromycin and amoxicillin achieved the highest (77.9%) success rate, whilst the lowest success rate (62.7%) was observed following the 14-day PPI, clarithromycin and tinidazole regimen. The overall efficacy of triple therapies significantly decreased from 75.7% to 72.1% in the last decade. Sequential (88.3% on 3431 patients), concomitant (88.8% on 376 patients), and the bismuth-based quadruple therapy with three-in-one capsule, containing bismuth subcitrate potassium (140 mg), metronidazole (125 mg), tetracycline (125 mg) (90.4% on 999 patients) achieved similarly high eradication rates, but data on concomitant are still limited. The bismuth-based was associated with the higher (38.7%) incidence of side-effects., Conclusions: Data found that all triple therapies, irrespective of drug combination and therapy duration, should be abandoned in Italy due to their unacceptable low success rates. Monitoring the efficacy of standard first-line therapies in other countries could be clinically useful for both patients and clinicians., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)

Background/aims: H. pylori treatment remains a challenge for clinicians, and a definite quote of patients require two or more treatments. We evaluated the efficacy of rifabutin-based therapy and Pylera® regimen as rescue therapies., Methods: Between January 2016 and December 2019, dyspeptic patients with at least one therapeutic failure observed in clinical practice received either a 12-day rifabutin-based triple therapy (esomeprazole 40 mg and amoxicillin 1 g, both twice daily, and rifabutin 150 mg once daily) or 10-day quadruple therapy with Pylera® (three in one capsule containing 140 mg bismuth subcitrate potassium, 125 mg metronidazole and 125 mg tetracycline). The eradication rates according to previous number of eradication failure therapies were calculated. The role antibiotic resistance pattern in H. pylori isolates was also investigated., Results: Data of 423 patients were available. A total of 270 patients were treated with rifabutin-based therapy, and the overall eradication rate was 61.9%. Pylera® therapy was administered to 153 patients and the cure rate was 88.3%. According to the number of previous therapeutic failures, the eradication rate for the rifabutin-based therapy was 68.3% as second-line and further decreased to 63.1% in fourth-line therapy. Following Pylera® regimen, the cure rate was 94.8% in second-line, and remained 89.6% in fourth-line therapy. Efficacy of rifabutin-based and Pylera® therapies significantly decreased when clarithromycin and levofloxacin resistance, respectively, were present., Conclusions: Our data documented a decreasing trend for rifabutin-based therapy efficacy according to previous therapy failures, whilst this did not occur for Pylera®., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Helicobacter pylori infection is the major risk factor associated with the development of gastric cancer. Currently, administration of standard antibiotic therapy combined with probiotics and postbiotics has gained significant attention in the management of H. pylori infection. In this work, the immunomodulatory effects of Lactobacillus crispatus-derived extracellular vesicles (EVs) and cell-free supernatant (CFS) were investigated on H. pylori-induced inflammatory response in human gastric adenocarcinoma (AGS) cells. L. crispatus-derived EVs were isolated by ultracentrifugation and physically characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Furthermore, the protein content of L. crispatus-derived EVs was also evaluated by SDS-PAGE. Cell viability of AGS cells exposed to varying concentrations of EVs and CFS was assessed by MTT assay. The mRNA expression of IL-1β, IL-6, IL-8, TNF-α, IL-10, and TGF-ß genes was determined by RT-qPCR. ELISA was used for the measurement of IL-8 production in AGS cells. In addition, EVs (50 μg/mL) and CFS modulated the H. pylori-induced inflammation by downregulating the mRNA expression of IL-1β, IL-6, IL-8, and TNF-α, and upregulating the expression of IL-10, and TGF-ß genes in AGS cells. Furthermore, H. pylori-induced IL-8 production was dramatically decreased after treatment with L. crispatus-derived EVs and CFS. In conclusion, our observation suggests for the first time that EVs released by L. crispatus strain RIGLD-1 and its CFS could be recommended as potential therapeutic agents against H. pylori-triggered inflammation., (© 2024. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

Objectives: Antimicrobial resistance to clarithromycin and metronidazole significantly affects the cure rate of standard therapies for Helicobacter pylori infection. We tested whether different MIC levels of resistance to these antibiotics play a role in therapeutic efficacy., Methods: This was a post hoc analysis of data from a therapeutic trial in which patients with antibiotic susceptibility testing (Etest) received first-line sequential therapy. The level of antibiotic resistance was classified according to MIC values into low (MIC from >0.5 to ≤8 for clarithromycin, and from >8 to ≤32 for metronidazole) and high (MIC from >8 to 256 mg/L for clarithromycin, and from >32 to 256 mg/L for metronidazole)., Results: Data from 1006 patients were included. There were 520 (51.7%) patients with susceptible strains, 136 (13.5%) with clarithromycin-resistant strains, 144 (14.3%) with metronidazole-resistant strains and 206 (20.5%) with clarithromycin-resistant and metronidazole-resistant strains. In the presence of double resistance, the cure rate was still high (38/41, 92.7%) when MIC levels were low and it was reduced (94/112, 83.9%) only when MIC levels of both antibiotics were high. The cure rates did not significantly differ between patients with single antibiotic-resistant strains, irrespective of MIC values, and those with susceptible strains., Conclusions: We found that MIC levels of resistance to either clarithromycin or metronidazole play a role in H. pylori therapy outcome and that bacterial resistance becomes relevant in vivo when clarithromycin-resistant and metronidazole-resistant strains have high MIC values for at least one of these antibiotics., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Helicobacter pylori eradication failure influences its antibiotic resistance., Aims: This study aimed to evaluate the effect of previous treatment failures on it, including the changes in the antibiotic resistance rates, minimal inhibitory concentration (MIC) distributions, and resistance patterns., Materials and Methods: This single-center retrospective study included 860 primary isolates and 247 secondary isolates. Antibiotic susceptibility testing was performed for amoxicillin, metronidazole, clarithromycin, levofloxacin, furazolidone, tetracycline, and rifampicin. The demographic data and detailed regimens were collected., Results: The primary resistance rates to amoxicillin, metronidazole, clarithromycin, levofloxacin, tetracycline, rifampin, and furazolidone were 5.93%, 83.84%, 28.82%, 26.28%, 0.35%, 1.16%, and 0%, while secondary were 25.10%, 92.31%, 79.76%, 63.16%, 1.06%, 3.19%, and 0%, respectively. The resistance rates to amoxicillin, metronidazole, clarithromycin, and levofloxacin increased significantly with the number of treatment failures accumulated, and showed a linear trend. The proportion of primary and secondary multidrug-resistant (MDR) isolates were 17.79% and 63.16%, respectively. The MIC values of amoxicillin, clarithromycin, and levofloxacin were elevated significantly with medication courses increased., Conclusion: The prevalence of amoxicillin, clarithromycin, levofloxacin, and metronidazole resistance would increase rapidly following first-line treatment failure, as well as the MIC values of them. Clinicians should pay great attention to the first-line treatment to cure H. pylori infection successfully., (© 2024 John Wiley & Sons Ltd.)

Background: The purpose of this analysis is to evaluate the antimicrobial susceptibility of eight drugs effective against Helicobacter pylori (H. pylori) strains and the genetic diversity of H. pylori virulence genes to foresee clinical outcomes in North India., Materials and Methods: Fifty-eight H. pylori strains isolated from patients suffering from various gastrointestinal (GI) diseases were included in the study. MICs of various antibiotics were determined by the agar dilution method. The chi-squared test and Fisher exact test were used to determine the p-value, which was considered significant at p-value ≤ 0.05. RStudio 4.0 was used to for the data visualization., Results: The prevalence of drug resistance was found to be: cefixime (CFM) (41.3%), furazolidone (FZD) (34.4%), amoxicillin (AMX) (20.7%), levofloxacin (LVFX) (70.7%), metronidazole (MTZ) (39.6%), tetracycline (TET) (20.7%), clarithromycin (CLA) (17.2%), and rifabutin (RIF) (17.2%). Out of 58 H. pylori strains, 3 were pan susceptible. There were H. pylori strains with single-drug resistance (21.8%, 12/55), dual resistance (30.9%, 17/55), triple resistance (20%, 11/55), and multidrug resistance (27.3%, 15/55). The resistance rate in MTZ, CLA and RIF were found to be significantly higher in females as compared to males (p = 0.005, p = 0.002, and p = 0.02), respectively. The resistance to TET exhibited significantly higher levels in gastritis compared to GERD, DU, and other disease groups (p = 0.04) respectively., Conclusion: TET, AMX, CLA, and RIF were found to be more effective antibiotics against H. pylori infections, whereas more studies are required to provide evidence on increasing resistance rate of LVFX., (© 2024 John Wiley & Sons Ltd.)

Background and Aims: Italian guideline suggests 10-day sequential or bismuth-based quadruple therapies for first-line Helicobacter pylori treatment. Comparison between these regimens is lacking. We assessed the efficacy of these therapies in clinical practice and evaluated the role of primary bacterial resistance toward clarithromycin and metronidazole., Patients and Methods: Consecutive patients with H. pylori infection were enrolled. Bacterial culture with antibiotics susceptibility testing was attempted in all cases. Patients received either a sequential therapy with esomeprazole 40 mg for 10 days plus amoxicillin 1000 mg for the first 5 days followed by clarithromycin 500 mg and tinidazole 500 mg (all twice daily) for the remaining 5 days, or bismuth-based therapy with esomeprazole 20 mg twice daily and Pylera 3 tablets four times daily for 10 days. H. pylori eradication was assessed by using C-urea breath test., Results: A total of 495 patients were enrolled. Following sequential (250 patients) and quadruple (245 patients) therapies, the eradication rate were 92 and 91%, respectively, at intention-to-treat analysis and 96 and 97%, respectively, at per protocol analysis. Overall, the pattern of bacterial resistance did not significantly affect the cure rate, but the presence of clarithromycin and metronidazole dual resistance tended to reduce the success rate of both sequential (84.8 vs. 90.1%; P=0.4) and quadruple (85 vs. 94.1%; P=0.06) therapies. Adverse events occurred more frequently with the quadruple than with sequential therapy (56.9 vs. 25.8%; P<0.001)., Conclusion: In our country, sequential and bismuth-based quadruple therapy achieved similarly high eradication rates as first-line treatments for H. pylori infection in clinical practice.

Purpose: Bacterial resistance toward the most used antibiotics is increasing in Helicobacter pylori strains worldwide. Emergence of multidrug resistance significantly affects the efficacy of standard therapy regimens. Therefore, monitoring for primary antimicrobial resistance is essential for H. pylori management in clinical practice., Methodology: H. pylori isolates obtained from patients consecutively observed in a single center were tested for primary resistance by using E-test method. Bacterial strains showing MIC values >0.5, >8 and >1 mg/L toward clarithromycin, metronidazole and levofloxacin, respectively, were considered resistant. The trend of antibiotic prevalence, either single or combined, during 2010-2016 was assessed., Results: Antibiotic susceptibility data were available in 1424 (82.3%) out of 1730 tested patients. The overall resistance for all the three antibiotics showed an increasing trend from 2010 to 2013 (clarithromycin: from 19% to 35.6%; metronidazole: from 33.6% to 45.3%; levofloxacin: from 19% to 29.7%; p < .001), when a plateau until 2016 was observed (clarithromycin: 35.9%; metronidazole: 40.2%; levofloxacin: 29.3%). A similar trend occurred for clarithromycin-metronidazole combined resistance rate (2010: 11.4%; 2013: 28.2%; 2016: 21.9%)., Conclusion: Our data suggest that prevalence of primary resistance in H. pylori isolates toward the most frequently used antibiotics probably reached a plateau in the last years.

Background and Aim: Not all the susceptibility-guided therapies for Helicobacter pylori (H. pylori) infection achieve excellent eradication rates. The aim of this study was to perform a systematic review and meta-analysis to identify the optimal regimen for H. pylori treatment based on antibiotic susceptibility., Methods: A systematic search was performed in multiple databases. Studies reporting eradication rates of H. pylori with susceptibility-guided therapies were selected. Meta-analysis was conducted to calculate the pooled eradication rate among the treatment regimens., Results: Forty-eight eligible studies with 101 susceptibility-guided treatment arms were included. The overall eradication rate in patients harboring susceptible strains was 95.0% (95% CI, 94.1-95.9%), but only 63.4% of treatment arms (64/101) achieved good eradication rates (≥ 90%). Pooled eradication rates in patients with susceptible strains were: 93.4% (95% CI, 92.0-94.8%) for clarithromycin, 99.0% (95% CI, 98.1-100%) for nitroimidazoles and 95.4% (95% CI, 93.6-97.2%) for fluoroquinolones. Among the arms using a triple therapy, 66.7% (28/42) using clarithromycin, 84.2% (16/19) using nitroimidazoles and 70.8% (17/24) using fluoroquinolones achieved good (≥ 90%) eradication rates. Of 13 arms using sequential therapy, ≥ 90% eradication was achieved in 14.3% (1/7) using clarithromycin, 25.0% (1/4) using nitroimidazoles and both arms (2/2) using fluoroquinolones., Conclusions: Susceptibility testing alone seemed insufficient to reliably attain high H. pylori cure rates. The eradication rate in patients with nitroimidazoles susceptible strains was higher than those of fluoroquinolones and clarithromycin., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Bismuth quadruple therapy (BQT) is the recommended rescue therapy for Helicobacter pylori (H. pylori) infection. This study aimed to assess the efficacy and safety of a 10-day BQT regimen in patients who failed previous therapies and were infected with multiresistant H. pylori strains MATERIALS AND METHODS: Helicobacter pylori-infected patients underwent endoscopy, culture, and susceptibility test for clarithromycin, metronidazole, and levofloxacin. Treatment with three-in-one capsule (Pylera®) four times daily and esomeprazole 20 mg twice daily for 10 days was administered. Treatment-emergent adverse events (TEAEs) were registered., Results: A total of 116 patients with persistent H. pylori infection following at least one eradication therapy attempt were treated. Overall, resistance toward clarithromycin was detected in 80% of strains, toward metronidazole in 70%, and levofloxacin in 47.5%, with dual or triple resistance in 72.5% of cases. An eradication rate of 81.0% (95% CI: 73.0-87.1) and 87.0% (95% CI: 79.4-92.1) at ITT and PP analyses, respectively, was achieved. The cure rate remained high until it was used as fourth-line regimen, while it dropped to low values (<67%) in those patients with more than 4 therapy failures. A total of 65.7% (95% CI: 56.4-74.0) patients complained of TEAEs., Conclusions: Our data found that bismuth-based quadruple regimen is effective as rescue therapy for curing patients infected with multiresistant H. pylori strains., (© 2017 John Wiley & Sons Ltd.)

Background and Aim: Helicobacter pylori infection is responsible for considerable morbidity and mortality worldwide and eradication rates are falling globally because of increasing antimicrobial resistance. However, there is a paucity of local data to guide the choice of eradication therapy in Australia. This study aimed to evaluate current Australian rates of H. pylori antibiotic resistance in patients who had failed prior eradication therapy., Methods: A retrospective analysis of routine culture and antibiotic susceptibility data from two pathology laboratories servicing multiple tertiary referral hospitals in Western Australia (WA) and South Australia (SA), between 2018 and 2022, was performed. Rates of antimicrobial resistance and prevalence of multiresistant isolates in both SA and WA were calculated and comparison of temporal trends and differences between the two states was conducted., Results: A total of 796 H. pylori isolates revealed a clarithromycin resistance rate of 82%, metronidazole 68%, amoxicillin 4.4% and tetracycline 0.5%. Resistance to levofloxacin was observed in 22% and rifampicin 14%. Rates of resistance to clarithromycin were lower in SA compared with WA (incidence rate ratio [IRR]: 0.69, P = 0.0001). Multiresistant isolates were discovered in 63% of patients, with lower rates in SA compared with WA (IRR: 0.74, P = 0.002)., Conclusion: This first multicentre, multistate study of H. pylori resistance in Australian patients exposed to prior therapy demonstrated high rates of antimicrobial resistance, including levofloxacin (>20%). This raises concern about recommending levofloxacin in empirical second-line therapies. Increased monitoring and awareness of current H. pylori resistance rates in Australia are needed to guide local eradication practices., (© 2023 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Helicobacter pylori ( H pylori ) eradication rates have declined globally, stressing the importance of antimicrobial susceptibility testing to inform treatment. Molecular tests such as next-generation sequencing (NGS) provide susceptibility data for the antibiotics used in the treatment of H pylori in a noninvasive, effective, and rapid manner. We obtained stool susceptibility testing using a novel NGS-based analysis and compared results with the current "gold standard" of gastric biopsy culture via agar dilution in 20 pediatric patients with evidence of H pylori in gastric biopsies. Stool NGS-based antimicrobial susceptibility analysis was highly concordant with agar dilution for no resistance (100% agreement), as well as clarithromycin, levofloxacin, and amoxicillin resistance (100%, 67%, and 100% agreement, respectively) but not concordant for metronidazole in our cohort of patients. Future studies involving a larger number of patients and geographical regions are needed to further validate this analysis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Antibiotic resistance of Helicobacter pylori (H. pylori) is increasing worldwide, with geographical variations, impacting the treatment outcomes. This study assessed the antibiotic resistance patterns of H. pylori in Vietnamese children., Materials and Methods: Symptomatic children undergoing gastroduodenoscopy at two tertiary Children's Hospitals in Ho Chi Minh City were recruited. Antral and corpus biopsies were obtained and cultured separately. Susceptibility to amoxicillin (AMO), clarithromycin (CLA), metronidazole (MET), levofloxacin (LEV), and tetracycline (TET) was determined using E-test. Polymerase chain reaction was performed on another antral biopsy to detect the urease gene, cytotoxin-associated gene A (cagA), vacuolating cytotoxin A (vacA) genotypes, and 23S rRNA mutations conferring CLA resistance., Results: Among 123 enrolled children, a high primary resistance rate was found for CLA (68.5%, 61/89), followed by LEV (55.1%), MET (31.5%), AMO (25.8%), and TET (1.1%). Secondary resistance rates were 82.1% (7/28), 71.4%, 53.6%, and 3.6% for CLA, LEV, MET, and TET, respectively. Multidrug resistance was frequent (67.7%), with common patterns including CLA + LEV (20.3%) and CLA + MTZ + LEV (15.2%). Heteroresistance was detected in eight children (6.5%). The A2143G mutation was detected in 97.5% (119/122) of children. 86.1% of children had positive cagA strains and 27.9% had multiple vacA genotypes. No factor was significantly associated with antibiotic resistance., Conclusions: The alarming rate of antibiotic resistance for H. pylori, especially for CLA, with emerging multi- and hetero-resistant strains, pose a major treatment challenge that precludes CLA use as empirical therapy. Biopsies from both antrum and corpus can improve H. pylori culture, allowing tailored treatment based on antimicrobial susceptibility., (© 2023 John Wiley & Sons Ltd.)

Cure rate following standard first-line regimens for Helicobacter pylori eradication is decreasing so several patients require two or more treatments. Antibiotic susceptibility-based therapy, advised in current guidelines, is largely impracticable in clinical practice. Some 'standard' regimens (triple therapies based on either levofloxacin or rifabutin, bismuth-based quadruple therapies, sequential, concomitant and hybrid therapies) were empirically used as rescue therapies. We performed a systematic review on recent studies carried out in European countries dealing with these regimens. A total of 24 studies, with 3804 patients, were identified. As second-line therapy, Pylera (89.2%) and sequential therapy (92.5%) achieved significantly higher cure rates as compared to all the other regimens. As third-line therapy, levofloxacin-based therapy (84.1%) and Pylera (83.6%) achieved similarly high cure rates, whereas standard, bismuth-based quadruple therapy (64.1%) achieved the lowest. As a rescue therapy, the success rate was close to 75% following all therapies used, with data on rifabutin-based regimen consolidated in the larger sample size. Overall, levofloxacin-amoxicillin triple therapy achieved higher eradication rates when the 14- rather than 10-day regimen was used (87.1 vs. 72.2%; P = 0.003). Among bismuth-based therapies, Pylera achieved a significantly higher eradication rate than standard quadruple therapy (88 vs. 67%; P < 0.0001). These data suggest that a wise 'therapeutic package' following first-line therapy could be Pylera, levofloxacin- and rifabutin-based therapy, as long as Pylera therapy was not used as a first-line regimen and levofloxacin-based regimen was administered for 14 days., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aimed to evaluate the efficacy and safety of vonoprazan (VPZ) versus proton pump inhibitor (PPI) in clarithromycin-based bismuth-containing quadruple therapy (C-BQT) for the treatment of Helicobacter pylori (H. pylori) eradication., Methods: Medical records of patients in whom H. pylori was eradicated between 1 July 2018 and 31 December 2021 were retrieved retrospectively from the Outpatient Unit of Qilu Hospital. Efficacy, safety, and compliance were compared between VPZ-based and PPI-based C-BQT, containing vonoprazan 20 mg or proton pump inhibitors (lansoprazole 30 mg or esomeprazole 20 mg), bismuth 220 or 200 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, twice daily for 2 weeks by 1:1 propensity score matching analysis. The trial was registed on ClinicalTrials.gov (registration no. NCT05301725)., Results: The H. pylori eradication rates of VPZ-based and PPI-based therapies were 88.8% (151/170) and 87.6% (149/170) in the intention-to-treat analysis, 94.1% (144/153) and 91.1% (144/158) in the per-protocol analysis, respectively. The noninferiority of VPZ to PPI was confirmed in all analyses (P < 0.001). The incidence of adverse events was 30.0% (51/170) and 27.1% (46/170) in the VPZ-based and PPI-based groups, respectively. VPZ-based and PPI-based therapies were well tolerated and showed good patient compliance without significant differences., Conclusions: VPZ-based therapy resulted in a satisfactory eradication rate and was well tolerated for H. pylori eradication, which are comparable to PPIs in C-BQT as a first-line treatment for H. pylori infection., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background and Aim: Most consensuses recommend culture-guided therapy as third-line Helicobacter pylori treatment. This study aimed to investigate the efficacies of culture-guided therapy and empirical therapy with high-dose proton pump inhibitor (PPI) in the H. pylori third-line treatment., Methods: Between August 2012 and October 2021, H. pylori-infected patients with at least two failed eradication attempts received anti-H. pylori therapy according to the results of antimicrobial sensitivity tests plus high-dose rabeprazole and/or bismuth. They were categorized into three groups: patients who had positive results of culture with equal to or more than three susceptible antibiotics were treated by culture-guided non-bismuth quadruple therapy, patients who had positive results of culture with one or two susceptible antibiotics were treated by culture-guided bismuth-containing therapy, and patients who had a negative result of culture were treated by an empirical therapy with high-dose rabeprazole plus amoxicillin, tetracycline and levofloxacin. A post-treatment assessment was conducted at week 8., Results: We recruited 126 patients. The eradication rates of culture-guided non-bismuth quadruple therapy (n = 50), culture-guided bismuth-containing therapy (n = 46) and empirical therapy (n = 30) were 84.0%, 87.0%, and 66.7% (95% confidence interval: 73.8-94.2%, 77.3-96.7%, and 49.8-83.6%), respectively. Overall, culture-guided therapy achieved a higher eradication rate than empirical therapy (85.4% vs 66.7%; 95% confidence interval, 0.4% to 37.0%, P = 0.022)., Conclusions: Culture-guided therapy with high-dose PPI achieves a higher eradication rate than empirical therapy with high-dose PPI in the third-line treatment of H. pylori infection. The eradication rate of rescue therapy with bismuth plus two susceptible antibiotics is not inferior to that with three susceptible antibiotics., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

This review summarizes important studies regarding Helicobacter pylori therapy published from May 2018 to May 2019. The main themes that emerge involve studies assessing the efficacy of bismuth-based regimens. While in recent years the efficacy of bismuth-based quadruple therapy as a second-line therapy has been clearly established, there is now substantial evidence that it is the best performing first-line therapy. Antibiotic resistance was again intensely studied this year, and a clear and dramatic increase in resistance is noted for clarithromycin and levofloxacin; most notably, it may not be possible to support these therapies in most regions of the world much longer without testing. The utility of vonoprazan as an alternative to proton-pump inhibitor therapy, especially in resistant and difficult to treat groups, has also been considered in greater detail this year, as well as means of supporting and enhancing adherence to therapy. Several studies showed that the diversity of gut microbiota was significantly altered shortly after H pylori eradication. However, the diversity was restored to pre-treatment state after 2 months in patients treated with triple therapy. More studies are warranted to assess the long-term changes of gut microbiota after H pylori eradication., (© 2019 John Wiley & Sons Ltd.)

Background: Variation in Helicobacter pylori (H. pylori) disease in terms of prevalence and antibiotic resistance prevails globally requiring a need to develop region-specific surveillance. We aimed to assess the influence of immigration factors upon the interpretation of local Singaporean epidemiological trends in antimicrobial susceptibility patterns and therapeutic outcomes in children with culture-positive H. pylori., Materials and Methods: We retrospectively analyzed eradication outcomes of children with culture-proven H. pylori infections between 2011 and 2020 at our center, and we also analyzed the antimicrobial susceptibility profiles of the corresponding H. pylori isolates. The cohort was classified into two groups: (1) Native Singaporeans and (2) Non-native Singaporeans (First-/Second-generation immigrants and Non-residents) to correlate with resistance patterns and eradication outcomes. H. pylori culture was done via Kirby-Bauer disk diffusion for the era 2011-2016 and bioMérieux E test for 2016-2020., Results: A total of 70 children (median age 14 [2-17] years) were included in the analysis. 42.9% (30/70) of the cohort displayed some form of antibiotic resistance; clarithromycin resistance was the most prevalent (30.0%), followed by metronidazole (27.5%) and amoxicillin (7.1%). Comparing to natives, non-native Singaporeans were significantly younger at presentation (mean 11.7 vs. 13.7 years, p = 0.043), and a significantly higher proportion of non-natives carried clarithromycin-resistant (51.4% vs. 8.6%, p < 0.001), metronidazole-resistant (47.1% vs. 8.6%, p < 0.001), or multidrug-resistant (resistant to ≥2 drugs) (40.0% vs. 2.9%, p < 0.001] strains. Non-natives were significantly more likely to fail first-line eradication therapy (48.5% failure vs. 23.3%, p = 0.038). The proportion of pan-sensitive H. pylori was significantly lower in first-generation (25.0%, p = 0.001) and second-generation (42.9%, p = 0.018) immigrants compared to natives (82.86%). These conclusions did not vary when the analysis was repeated for each culture method., Conclusions: An antibiotic susceptibility-based approach should be advocated for all patients but especially so for non-natives, who are at higher risk for antimicrobial resistant strains and poorer eradication outcomes., (© 2021 John Wiley & Sons Ltd.)

Background: The aim of this study was to evaluate the efficacy and safety of bismuth pectin capsules and bismuth pectin granules in the first-line quadruple treatment of Helicobacter pylori (H. pylori)., Methods: This study was a multicenter, randomized, open-labelled controlled clinical trial. Patients with a H. pylori infection were randomized into 4 groups (1:1:1:1) and treated with a 14-day bismuth-containing quadruple therapy. The 4 groups received either bismuth potassium citrate capsules (220 mg), colloidal bismuth pectin capsules (200 mg), bismuth pectin granules (150 mg), or bismuth pectin granules (300 mg). The primary outcome was the eradication rate of H. pylori. The secondary outcomes included symptom improvement, patient compliance, and incidence of adverse events. This study was registered at ClinicalTrials.gov (NCT04209933)., Results: A total of 240 patients were included in this study, and 211 patients completed the follow-up. An intention-to-treat analysis showed that the H. pylori eradication rates of the 4 groups were 73.3%, 76.7%, 75.0%, and 71.7%, respectively. The per-protocol analysis showed that the H. pylori eradication rates of the 4 groups were 86.3%, 82.1%, 83.3%, and 86.0%. There was no significant difference among the 4 groups in the H. pylori eradication rate (P > .05). There were also no significant differences in the symptom improvement rate, overall adverse reaction rate, or patient compliance among the 4 groups., Conclusions: Bismuth pectin capsules and bismuth pectin granules had similar efficacy and safety for H. pylori eradication compared to bismuth potassium citrate. These data suggest that bismuth pectin can be an alternative to bismuth potassium citrate to eradicate H. pylori when using bismuth-containing quadruple therapy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Probiotics may alter the gut microbiota and may reduce antibiotic-related dysbiosis after H. pylori eradication. However, whether probiotics are effective in reducing the bacterial load of H. pylori and modifying the gut microbiota remains unknown. We aimed to assess the efficacy of Lactobacillus acidophilus and Lactobacillus rhamnosus in reducing the bacterial load of H. pylori and modifying the gut microbiota., Materials and Methods: In this double-blind, randomized, placebo-controlled trial, we recruited 40 adult subjects with moderate to high bacterial loads of H. pylori, defined as a mean delta over baseline (DOB) value of the 13 C-urea breath test ( 13 C-UBT) of 10 or greater every 4 days 6 times. Eligible subjects were randomized in a 1:1 ratio to receive either probiotics containing Lactobacillus acidophilus and Lactobacillus rhamnosus or placebo twice daily for 4 weeks. 13 C-UBT was measured weekly from the beginning of treatment to 2 weeks after treatment. Amplification of the V3 and V4 hypervariable regions of the 16S rRNA was performed for fecal microbiota., Results: A total of 40 subjects were randomized to receive probiotics or placebo. The DOB value was significantly lower in the probiotic group than in the placebo group after 4 weeks of treatment (26.0 vs. 18.5, p = .045). The DOB value was significantly reduced compared to that at baseline in the probiotic group (18.5 vs. 26.7, p = .001) but not in the placebo group (26.0 vs. 25.0, p = .648). However, the eradication rate for H. pylori was 0% in both groups. There was no significant difference in the DOB values between the two groups 1 and 2 weeks after discontinuation of the probiotics. There were also no significant changes observed in the α-diversity and β-diversity at week 4 compared to baseline in the probiotic group (p = .77 and 0.91) and the placebo group (p = .26 and 0.67)., Conclusions: Although the use of Lactobacillus acidophilus and Lactobacillus rhamnosus may reduce the bacterial load of H. pylori, there were no significant changes in the composition of gut microbiota. This trial is registered with ClinicalTrials.gov, NCT02725138., (© 2021 John Wiley & Sons Ltd.)

Helicobacter pylori (H. pylori) infection is associated with the development of multiple diseases. The eradication rate of H. pylori has gradually decreased, suggesting the need to discover more effective therapies. This study aimed to compare the effectiveness of first-line treatments including high-dose dual therapy (HDDT), bismuth-based quadruple therapy (BQT), sequential therapy (ST), concomitant therapy (CT) and hybrid therapy (HT) by network meta-analysis (NMA). A comprehensive search on PubMed, Embase, Cochrane Library and Web of Science, was performed from their inception to 1 September 2019. A network analysis of randomized controlled trials (RCTs) comparing first-line therapies were carried out using Stata 14.0 and Revman 5.2. Moreover, a sensitivity analysis was conducted by omitting non-Asian studies. Finally, 41 RCTs with 14 119 patients were included. The NMA showed that, in terms of eradication rate, ST for 10 days (ST-10) was significantly lower than CT for 10 or 14 days (CT ≥ 10). Sensitivity analysis among the Asian population showed that ST-10 denoted the lowest effectiveness among the interventions. The ranking results based on probability showed that HDDT ranked first for the eradication rate. As for adverse events, HDDT was significantly less than BQT and CT regardless of duration, while BQT for 14 days represented higher adverse events than ST, HT and CT ≥ 10. HDDT ranked first among the therapies. In conclusion, HDDT for 14 days appeared to be the most optimal first-line therapy for H. pylori among the Asian population with comparable efficacy and compliance but causing fewer adverse events., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Bismuth quadruple (BQT) and non-bismuth quadruple (N-BQT) therapies are the recommended first-line treatments for Helicobacter (H.) pylori infection., Objective: To compare the efficacy of BQT and N-BQT in clinical practice in an area with high clarithromycin resistance, choosing the regimen on the basis of previous exposure to clarithromycin., Methods: A total of 404 consecutive H pylori-positive, naïve patients were enrolled. A total of 203 patients without previous exposure to clarithromycin received N-BQT, 100 patients for 10 days and 103 for 14 days, whereas 201 with previous exposure to clarithromycin received 10-day BQT. Efficacy and treatment-related adverse events were assessed., Results and Conclusions: Eradication rates by intention-to-treat analysis were 88.2% for N-BQT and 91.5% for BQT (P = .26); per-protocol analysis eradication rates were 91.2% and 95.8% for N-BQT and BQT, respectively (P = .07). Eradication rates were significantly higher with 14-day than 10-day CT (P < .003). Almost all patients had a good compliance with both N-BQT (95.6%) and BQT (95%). Adverse events occurred in 24.1% and 26.9% (P = .53) of patients in the N-BQT and BQT group, respectively. In conclusion, clarithromycin-containing non-bismuth or bismuth quadruple therapy, based on the knowledge of previous clarithromycin exposure, is effective and safe even in an area of high prevalence of clarithromycin-resistant H pylori strains., (© 2020 John Wiley & Sons Ltd.)

Background: The occurrence of antibiotic-resistant strains has been rapidly increasing due to the wide use of antibiotics. To evaluate the current effects of antibiotic resistance on Helicobacter pylori eradication efficacy, we conducted this systematic review and meta-analysis., Methods: Literature searches were conducted in the following databases: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Statistical analysis was performed using STATA version 12.0 (StataCorp LP, College Station, TX, USA)., Results: A total of 120 studies, including 28 707 patients, were assessed. Only first-line therapy was considered. The pooled RR of eradication rate in patients with Helicobacter pylori strains sensitive versus resistant to clarithromycin was 0.682 (95% CI: 0.636-0.731). The pooled RR of eradication rate in patients with Helicobacter pylori strains sensitive versus resistant to metronidazole was 0.843 (95% CI: 0.810-0.877). The pooled RR of eradication rate in patients with Helicobacter pylori strains sensitive versus resistant to levofloxacin was 0.794 (95% CI: 0.669-0.941). The pooled RR of eradication rate in patients with Helicobacter pylori strains sensitive versus resistant to dual clarithromycin and metronidazole was 0.674 (95% CI: 0.590-0.770)., Conclusion: Antibiotic resistance causes a decrease in the eradication rate of H pylori today. Quadruple concomitant therapy may overcome the declining H pylori eradication rate caused by metronidazole-only resistance., (© 2020 John Wiley & Sons Ltd.)

Background: Antimicrobial resistance of Helicobacter pylori (H pylori) affects the efficacy of eradication therapy. The aim of this study was to estimate the prevalence of primary and secondary resistance of H pylori isolates to antibiotics in Korea., Methods: The present study was performed from 2003 to 2018. Primary resistance was evaluated in 591 patients without any history of eradication and secondary resistance in 149 patients from whom Helicobacter pylori was cultured after failure of eradication. A minimal inhibitory concentration test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and rifabutin using the agar dilution method., Results: An increase in the primary resistance rate was found in clarithromycin (P < .001), metronidazole (P < .001), and both levofloxacin (P < .001) during the study period. The primary resistance rates of amoxicillin and tetracycline were low and stable during the study period. The secondary resistance rate significantly increased in metronidazole and levofloxacin (P = .022 and .039, respectively)., Conclusions: The primary and secondary resistance rates of clarithromycin, metronidazole, and levofloxacin for Helicobacter pylori in Korea were high and increased over time. However, the primary and secondary resistance rates of amoxicillin and tetracycline were low and stable over time. These results will help in selecting effective eradication regimens of H pylori in Korea in the future., (© 2019 John Wiley & Sons Ltd.)

Background/Objectives: Stomach infections by Helicobacter pylori can cause acute or chronic gastritis, peptic ulcers, and gastric cancer. The rise in antibiotic resistance is a significant health issue highlighted by the World Health Organization. The increasing number of treatment failures underscores the necessity for antibiotic susceptibility testing (AST). The study aimed to investigate the current prevalence and resistance to fluoroquinolones and clarithromycin with their detected mutations. Methods: Stomach biopsies from symptomatic patients were subjected to molecular testing by GenoType Helico DR kit (Hain Lifescience GmbH, Nehren, Germany). Results: Positive findings on the presence of H. pylori were detected in 42.4% of symptomatic patients, with the significant majority of patients (69%) having previously failed treatments. The resistance rates to fluoroquinolones and clarithromycin were 53.9% and 58.5%, respectively, with significantly higher rates in secondary resistant strains. The main resistance markers in fluoroquinolones and clarithromycin were N87K (27.4%) and A2147G (78.6%), respectively. Hetero-resistance or mixed genotypes were detected in over 20% of tested patients. During the study period, a significant increase in trends in both fluoroquinolones and clarithromycin resistance rates was observed. Conclusions: Results indicate the need for the implementation of the latest Maastricht VI Consensus recommendations for both AST whenever possible and the use of tailored guided therapy options due to high resistance rates and possible treatment failures. The GenoType Helico DR kit is a useful tool for AST, especially in cases of mixed H. pylori genotypes. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) is a bacterium known to be associated with a significant risk of gastric cancer in addition to chronic gastritis, peptic ulcer, and MALT lymphoma. Although only a small percentage of patients infected with H. pylori develop gastric cancer, Gastric cancer causes more than 750,000 deaths worldwide, with 90% of cases being caused by H. pylori. The eradication of this bacterium rests on multiple drug regimens as guided by various consensus. However, the efficacy of empirical therapy is decreasing due to antimicrobial resistance. In addition, biofilm formation complicates eradication. As the search for new antibiotics lags behind the bacterium's ability to mutate, studies have been directed toward finding new anti-H. pylori agents while also optimizing current drug functions. Targeting biofilm, repurposing outer membrane vesicles that were initially a virulence factor of the bacteria, phage therapy, probiotics, and the construction of nanoparticles might be able to complement or even be alternatives for H. pylori treatment. This review aims to present reports on various compounds, either new or combined with current antibiotics, and their pathways to counteract H. pylori resistance. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) infection is a widespread global health issue with a varying prevalence influenced by geography, socioeconomic status, and demographics. In the U.S., the prevalence is lower, though certain groups, such as older adults and immigrants from high-prevalence regions, show higher rates. The decrease in infection rates in developed countries is due to improved sanitation, antibiotics, and healthcare, whereas developing countries continue to experience high rates due to poor living conditions. H. pylori infection can be asymptomatic or cause symptoms like dyspepsia, abdominal pain, bloating, nausea, and loss of appetite. Pathophysiologically, H. pylori contribute to conditions such as gastritis, peptic ulcers, and gastric cancer through mechanisms including urease production and the release of virulence factors, leading to chronic inflammation and an increased cancer risk. Diagnostic methods for H. pylori have progressed significantly. Non-invasive techniques, such as serological assays, stool antigen tests, and urea breath tests, are practical and sensitive. Invasive methods, including endoscopic biopsy and molecular diagnostics, are more definitive but resource intensive. Recent advancements in diagnostic technology, including matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), biosensor technology, and next-generation sequencing (NGS), promise improved speed, accuracy, and accessibility. These innovations are expected to enhance the detection and management of H. pylori, potentially reducing the global disease burden. This review aims to discuss these diagnostic modalities with a focus on further advances under investigation. [ABSTRACT FROM AUTHOR]

Clarithromycin (CLR) is currently a key antibiotic for Helicobacter pylori infection treatment, however, the data on CLR resistance patterns in Russia are missing. Here, we applied WGS-based approach to H. pylori clinical isolates from Russia to comprehensively investigate sequence variation, identify putative markers of CLR resistance and correlate them with phenotypic susceptibility testing. The phenotypic susceptibility of 44 H. pylori isolates (2014–2022) to CLR was determined by disc diffusion method: 23 isolates were CLR-resistant and 21-CLR-susceptible. All isolates were subjected to WGS and submitted to GenBank. Based on complete sequence analysis, we showed that among all sequence variants, the combination of mutations A2146G/A2147G in the 23S rRNA gene is the most reliable for prediction of phenotypic susceptibility. For the first time, the average number of mutations in 106 virulence-associated genes between resistant and susceptible groups were compared. Moreover, this study presents the first WGS insight into genetic diversity of H. pylori in Russia with a particular focus on the molecular basis of drug resistance: the novel mutations were described as potential markers for the resistance development. Of these, the most prominent was a frameshift deletion (252:CGGGT) in HP0820 coding region, which is a good candidate for further investigation. [ABSTRACT FROM AUTHOR]

Helicobacter pylori infection affects over half of the world's population and is a global health concern because it contributes to chronic and fatal gastrointestinal disorders, including peptic ulcer disease and gastric cancer. The escalating prevalence of antibiotic-resistant strains of H pylori necessitates a change in management. The conventional strategy of empiric-based treatments is becoming increasingly ineffective in both adult and pediatric populations; rates of eradication to common first-line regimens remain suboptimal and continue to decline. Culture-based susceptibility testing for H pylori has been underutilized and challenging to incorporate into practice. Next-generation sequencing (NGS), which can identify the genetic biomarkers that predict antimicrobial resistance and susceptibility patterns, offers a promising alternative. NGS may enable clinicians to tailor individual treatment regimens and contribute to epidemiologic surveillance across populations. As NGS technology advances and becomes more accessible, its integration into routine clinical practice holds the potential to transform H pylori management strategies and improve patient outcomes. This article reviews the literature describing antimicrobial resistance patterns in adult and pediatric practice in the United States and provides practical guidance on the current role of NGS in the management of H pylori. [ABSTRACT FROM AUTHOR]

Probiotics are natural microbial agents with beneficial properties such as bacteriostatic and anti-infective properties. Lactobacillus plantarum Q21, Q25 and QA85, were isolated from the Chinese specialty fermented food "Jiangshui" and proved to be highly resistant to Helicobacter pylori (p < 0.0001). In vitro results showed that Q21, Q25 and QA85 strongly inhibited H. pylori and could specifically co-aggregate H. pylori in vitro (more than 56%). Strains have the potential to adhere to cells and hinder H. pylori colonization (p < 0.0001). To assess the anti-H. pylori efficacy of strains in vivo, volunteers were recruited and a self-controlled study of probiotic intervention was conducted. Compared to pre-probiotics, volunteers who took Q21, Q25 and QA85 for 1 month showed significant improvement in discomfort, a significant reduction in GSRS scores (p < 0.05), and modulation of inflammatory response (p < 0.05). Q21, Q25 and QA85 resulted in a decreasing trend of H. pylori load in volunteers (454.30 ± 327.00 vs. 328.35 ± 237.19, p = 0.06). However, the strains were not significantly effective in modulating the imbalance of the gut microbiota caused by H. pylori infection. In addition, strains affect metabolic pathways by increasing the levels of O-Phosphoethanolamine and other related metabolites, which may ameliorate associated symptoms. Therefore, Lactobacillus plantarum Q21, Q25 and QA85 can be regarded as a candidate probiotic preparation that exerts direct or indirect anti-H. pylori effects by inhibiting H. pylori activity and colonization, reducing inflammation and discomfort, maintaining homeostasis in the internal environment, affecting the metabolic pathways and repairing the body barrier. They can play a role in relieving H. pylori infection. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori is the most frequent human bacterial infection worldwide; it is prevalent in approximately half of the world's population. H.pylori poses a major health risk because it possesses distinct virulence factors and highly resistant to antibiotics. Multidrug resistance (MDR) and single-drug resistance are two distinct resistance profiles. Chromosome mutations influence antibiotic activity via target-mediated pathways. Inadequate drug absorption, efflux pumps activity, biofilm development, and cocci formation represent supplementary biological mechanisms by which H.pylori acquires drug resistance. The overexpression of efflux pumps genes in mutant isolates is readily detectable in post-therapy courses. Objective: Characterization of the biological and molecular mechanisms contributing to the development of antibiotic resistance in H.pylori. Conclusion: An alarming rate of drug-resistant H.pylori is on the rise. Primary and acquired resistance to clarithromycin and metronidazole has increased globally. Bacterial factors including biofilms, efflux pumps, and molecular mechanism are in association with H.pylori resistance. It is important to continue to monitor the resistance profiles of H.pylori isolates. [ABSTRACT FROM AUTHOR]

The management of gastric Helicobacter pylori (H. pylori) infection represents a significant concern in primary healthcare. This survey evaluates the approaches, attitudes, and knowledge regarding gastric H. pylori infection among Italian general practitioners (GPs) and young doctors undergoing general practice training (ITGPs). The survey enrolled 466 GPs and 70 ITGPs. Among GPs, specialist recommendations and the Maastricht–Florence guidelines were frequently referenced sources, while ITGPs relied more on the Maastricht–Florence guidelines and internet resources. ITGPs demonstrated more proactive approaches than GPs in investigating and treating conditions such as gastric ulcers, atrophic gastritis, and iron-deficiency anemia. However, there was limited attention given to the role of H. pylori treatment in first-degree relatives of gastric cancer patients. The most used diagnostic methods were the urea breath test and fecal test. Triple therapy was the most frequently chosen initial treatment regimen, with quadruple bismuth therapy becoming the primary option after initial treatment failure, followed by quinolone therapy and concomitant therapy. This survey underscores a disparity between real-world practices and the recommendations outlined in current guidelines, indicating a need for improved understanding of H. pylori guidelines among both GPs and ITGPs. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) infection is a prevalent global health issue, associated with several gastrointestinal disorders, including gastritis, peptic ulcers, and gastric cancer. The landscape of H. pylori treatment has evolved over the years, with increasing challenges due to antibiotic resistance and treatment failure. Traditional diagnostic methods, such as the urea breath test, stool antigen test, and endoscopy with biopsy, are commonly used in clinical practice. However, the emergence of antibiotic-resistant strains has led to a decline in treatment efficacy, necessitating a re-evaluation of common diagnostic tools. This narrative review aims to explore the possible changes in the diagnostic approach of H. pylori infection in the era of treatment failure. Molecular techniques, including polymerase chain reaction and whole genome sequencing, which have high sensitivity and specificity, allow the detection of genes associated with antibiotic resistance. On the other hand, culture isolation and a phenotypic antibiogram could be used in the diagnostic routine, although H. pylori is a fastidious bacterium. However, new molecular approaches are promising tools for detecting the pathogen and its resistance genes. In this regard, more real-life studies are needed to reveal new diagnostic tools suitable for identifying multidrug-resistant H. pylori strains and for outlining proper treatment. [ABSTRACT FROM AUTHOR]

Concomitant therapy (CT) and bismuth quadruple therapy (BQT) are recommended in geographical areas with high clarithromycin resistance for Helicobacter pylori (H. pylori) eradication. We compared CT and BQT as the first lines of treatment in a randomized controlled trial. Consecutive patients with H. pylori diagnosed by concordance of both a urea breath test and histology were recruited. For BQT, patients received 3 PyleraTM capsules q.i.d.; for CT, 1000 mg of amoxicillin b.i.d, 500 mg of clarithromycin b.i.d and 500 mg of metronidazole b.i.d. As a proton pump inhibitor, 40 mg of pantoprazole b.i.d was administered. Both regimens lasted 10 days. In total, 46 patients received CT and 38 BQT. Both groups were comparable for age (p = 0.27) and sex (p = 0.36). We did not record any drop outs; therefore, the intention to treat and per protocol rates coincided. The most common symptoms were heartburn and post-prandial fullness, which were equally present in both groups. The success rate was 95.6% for CT and 100% for BQT (p = 0.56). Side effects were recorded in 23.9% and 31.6% of patients in the CT and BQT arms, respectively (p = 0.47). The most common ones were abdominal pain (8) and diarrhea (6). In conclusion, CT and BQT are equally effective in our area with high clarithromycin resistance, southern Italy, and showed comparable safety. [ABSTRACT FROM AUTHOR]

Background and aim: We conducted an equivalence trial of quadruple non-bismuth "concomitant" and "hybrid" regimens for H. pylori eradication in a high clarithromycin resistance area. Methods: There were 321 treatment-naïve H. pylori-positive individuals in this multicenter clinical trial randomized to either the hybrid (esomeprazole 40 mg/bid, amoxicillin 1 g/bid for 7 days, then 7 days esomeprazole 40 mg/bid, amoxicillin 1 g/bid, clarithromycin 500 mg/bid, and metronidazole 500 mg/bid) or the concomitant regimen (all medications given concurrently bid for 10 days). Eradication was tested using histology and/or a 13C-urea breath test. Results: The concomitant regimen had 161 patients (90F/71M, mean 54.5 years, 26.7% smokers, 30.4% ulcer) and the hybrid regimen had 160 (80F/80M, mean 52.8 years, 35.6% smokers, 31.2% ulcer). The regimens were equivalent, by intention to treat 85% and 81.8%, (p = 0.5), and per protocol analysis 91.8% and 87.8%, (p = 0.3), respectively. The eradication rate by resistance, between concomitant and hybrid regimens, was in susceptible strains (97% and 97%, p = 0.6), clarithromycin single-resistant strains (86% and 90%, p = 0.9), metronidazole single-resistant strains (96% and 81%, p = 0.1), and dual-resistant strains (70% and 53%, p = 0.5). The side effects were comparable, except for diarrhea being more frequent in the concomitant regimen. Conclusions: A 14-day hybrid regimen is equivalent to a 10-day concomitant regimen currently used in high clarithromycin and metronidazole resistance areas. Both regimens are well tolerated and safe. [ABSTRACT FROM AUTHOR]

Little evidence has been published regarding the antimicrobial resistance patterns of Helicobacter pylori (H. pylori) strains in Northwestern and Central Romania. The aim of this study was to determine the antibiotic resistance pattern of H. pylori isolates from gastric biopsies collected from patients living in Romania using ETEST® and GenoType HelicoDR. Gastric biopsies were obtained from 148 adult patients, 87 women and 61 men, the majority (131 patients) from Northwestern and Central Romania. Sixty-nine H. pylori strains were detected by both culture and PCR; sixty-three biopsies were negative by both techniques; one biopsy was positive by culture but negative by PCR; and fifteen biopsies were negative by culture but positive by PCR. Primary resistance against clarithromycin, fluoroquinolones, and metronidazole was found in 16.7%, 11.1%, and 13.3% of strains, respectively. No primary resistance has been detected against amoxicillin, tetracycline, and rifampicin. Secondary resistance against clarithromycin, fluoroquinolones, metronidazole, amoxicillin, tetracycline, and rifampicin was found in 75.8%, 30.3%, 65.5%, 1.8%, 1.8%, and 7.3% of the strains, respectively. The most frequent clarithromycin-resistant genotype detected by GenoType HelicoDR was A2147G (62.3%). Concordances between ETEST® and PCR for clarithromycin and fluoroquinolones were 85.5% and 78.3%, respectively. Further investigation of H. pylori resistance should be conducted to ensure proper eradication schemes. [ABSTRACT FROM AUTHOR]

This document discusses the issue of antibiotic resistance in Helicobacter pylori (H. pylori) infection, a common bacterial infection that affects approximately half of the world's population. Antibiotic resistance is a major cause of treatment failure for H. pylori infection, and new strategies are needed to improve treatment and management techniques. The document includes various studies and reviews that explore different approaches to combat antibiotic resistance, such as probiotic supplementation, engineered antimicrobial peptides, global-scale studies of resistance genes, and the use of culture-based susceptibility testing. Additionally, the document discusses the challenges and opportunities of using metagenomic and metatranscriptomic approaches to assess antimicrobial resistance profiles, as well as potential strategies for effective management of H. pylori infections in different regions, including Africa. The document also highlights the development of a microtiter plate-based drug screening method and the potential of targeted delivery approaches and nanotechnology-based strategies. Finally, the document suggests the need for an effective DNA-based vaccine for H. pylori and explores the use of a nano-emulsion system for improved efficacy against the infection. [Extracted from the article]

The present study was to evaluate the diagnostic accuracy of different types of PCR tests with the aim of determining which one performs best for detecting Helicobacter pylori in stool samples. Related articles were searched from PubMed, Embase, Web of Science databases, Scopus, and Scholar Google. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool and RevMan5.4 software. Pooled sensitivity, specificity, DOR, PLR and NLR for the stool PCR test in detecting H. pylori infection were performed by Stata 15.0 software. Subgroup meta-analysis was performed by Open Meta-analyst software. Ten studies were selected in this study. Stool PCR test had 92.0 % (83.0, 96.0 %) pooled sensitivity, 96.0 % (84.0, 99.0 %) pooled specificity, 296.0 (51.6, 1,696.9) pooled DOR, 26.1 (5.3, 128.7) pooled PLR and 0.09 (0.04, 0.18) NLR in the diagnosis of H. pylori infection, and summary receiver operating characteristic curve (SROC) illustrated an area under the curve (AUC) of 0.98. Subgroup meta-analysis showed rtPCR as having the highest diagnostic accuracy. Our results identify rtPCR as having the highest diagnostic accuracy for the detection of H. pylori in stool samples, and the stool PCR test as a reliable diagnostic tool for H. pylori infection. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) is the most common chronic bacterial infection, affecting approximately half of the world's population. H. pylori is a Class I carcinogen according to the World Health Organization, and the International Agency for Research on Cancer (IARC) has linked it to 90% of stomach cancer cases worldwide. The overall pattern points to a yearly reduction in eradication rates of H. pylori with the likelihood of success further decreasing after each unsuccessful therapeutic effort. Antimicrobial resistance in Helicobacter pylori is a major public health concern and is a predominant cause attributed to eradication failure. As a result, determining H. pylori's antibiotic susceptibility prior to the administration of eradication regimens becomes increasingly critical. Detecting H. pylori and its antimicrobial resistance has traditionally been accomplished by time-consuming culture and phenotypic drug susceptibility testing. The resistance of H. pylori to different antibiotics is caused by various molecular mechanisms, and advances in sequencing technology have greatly facilitated the testing of antibiotic susceptibility to H. pylori. This review will summarize H. pylori antibiotic resistance patterns, mechanisms, and clinical implications. We will also review the pros and cons of current antibiotic susceptibility testing methods. Along with a comparison of tailored susceptibility-guided regimens and empirical therapy based on the latest evidence, an evidence-based approach to such situations will be explored. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Despite the declining trend of Helicobacter pylori (H. pylori) prevalence around the globe, ongoing efforts are still needed to optimize current and future regimens in view of the increasing antibiotic resistance. The resistance of H. pylori to different antibiotics is caused by different molecular mechanisms, and advancements in sequencing technology have come a far way in broadening our understanding and in facilitating the testing of antibiotic susceptibility to H. pylori. In this literature review, we give an overview of the molecular mechanisms behind resistance, as well as discuss and compare different antibiotic susceptibility tests based on the latest research. We also discuss the principles of antibiotic stewardship and compare the performance of empirical therapies based on up-to-date resistance patterns and susceptibility-guided therapies in providing effective H. pylori treatment. Studies and clinical guidelines should ensure that the treatment being tested or recommended can reliably achieve a pre-agreed acceptable level of eradication rate and take into account the variations in antibiotic resistance across populations. Local, regional and international organizations must work together to establish routine antibiotic susceptibility surveillance programs and enforce antibiotic stewardship in the treatment of H. pylori, so that it can be managed in a sustainable and efficient manner. [ABSTRACT FROM AUTHOR]

Antibiotic resistance (AMR) is an alarming concern worldwide and Helicobacter pylori, one of the most prevalent bacteria, is not an exception. With antibiotics being its primary therapy, increasing resistance leads to a higher rate of treatment failure. Understanding the genomic mechanisms of resistance to clarithromycin, levofloxacin, metronidazole, amoxicillin, tetracycline, and rifampicin through next-generation sequencing-based molecular tools, such as whole genome sequencing (WGS), can be of great value, not only to direct a patient's treatment, but also to establish and optimize treatment guidelines according to the local epidemiology and to avoid the use of inappropriate antibiotics. WGS approaches allow us to gain insight into the genomic determinants involved in AMR. To this end, different pipelines and platforms are continuously being developed. In this study, we take a more detailed view of the use and progression of WGS for in-depth study of H. pylori's AMR. [ABSTRACT FROM AUTHOR]

Background: New treatment strategies are required against infections caused by Helicobacter pylori, which grows increasingly resistant to antibiotics. Polymerase chain reaction-based methods for antibiotic susceptibility testing are available for detecting H. pylori-specific mutations that confer resistance to clarithromycin and levofloxacin. Several meta-analyses have compared eradication rates for susceptibility-guided versus empirical therapy for H. pylori treatment; however, all have significant limitations and high heterogeneity, and the results are contradictory. The main objective of this trial is to assess whether a sequential strategy based on molecular susceptibility testing-guided therapy for H. pylori has a better eradication rate than empirical therapy. Methods: This trial is designed as a prospective, randomised, open-label, active-controlled and single-centre study. Men and women who are H. pylori-positive, naïve to treatment, and aged 18–65 years will be recruited. A total of 500 participants will be randomised to receive either empirical therapy or a susceptibility-guided sequential strategy. Bismuth quadruple therapy will be the empirical first-line therapy, and in case of failure, high-dose dual (proton-pump inhibitor + amoxicillin) treatment will be the rescue therapy. For the susceptibility-guided sequential strategy, regimen selection will be based on H. pylori susceptibility to clarithromycin (first-line) and levofloxacin (rescue). A first-line treatment of clarithromycin triple therapy will be selected for clarithromycin-sensitive strains. For clarithromycin resistance, a high-dose dual therapy will be selected. During the rescue treatment, a levofloxacin quadruple regimen will be selected for levofloxacin-sensitive strains, and a furazolidone quadruple regimen will be selected for others. The primary outcome is the first-line eradication rate in both groups, and the overall (including first and rescue therapies) H. pylori eradication rate in both groups is one of the secondary outcomes. The eradication rates of H. pylori will be analysed by intention-to-treat analysis, modified intention-to-treat analysis, and per-protocol analysis. Discussion: This randomised controlled trial will provide objective and valid evidence about the value of polymerase chain reaction-based molecular methods for antibiotic susceptibility testing in guiding H. pylori eradication. Trial registration: Clinicaltrials.gov NCT05549115. Released on 18 September 2022. First posted on 22 September 2022. Enrolment of the first participant on 20 September 2022. The study is retrospectively registered. [ABSTRACT FROM AUTHOR]

Background:Helicobacter pylori (H. pylori) is the most common chronic bacterial infection. Treatment effectiveness remains a subject of debate considering bacterial antimicrobial resistance. Our aim was to analyze the diagnostic methods and eradication treatments for H. pylori infection in Serbia. Methods: An observational multicenter prospective study was conducted in Serbia, as part of the European Registry on H. pylori Management (Hp-EuReg). Demographics, treatment indication, diagnostic methods, previous eradication attempts, and treatment were collected at AEG-REDCap e-CRF. Modified intention-to-treat (mITT) and per-protocol (PP) effectiveness analyses were performed. Safety, compliance, and bacterial antimicrobial resistance rates were reported. Data were quality checked. Results: Overall, 283 patients were included, with a mean age of 55 ± 15 years. Dyspepsia (n = 214, 77%) was the most frequent treatment indication, and histology (n = 144, 51%) was the most used diagnostic method. Overall eradication rate was 95% (PP) and 94% (mITT). Most prevalent first-line therapy was quadruple PPI + clarithromycin + amoxicillin + metronidazole, with a 96% effectiveness (p < 0.001). Second-line main treatment choice was triple amoxicillin + levofloxacin, with a 95% effectiveness (p < 0.05). Single-capsule Pylera® was the most prescribed third-line therapy, with 100% effectiveness (p < 0.05). Longer treatment duration was associated with a higher eradication rate in first-line therapy (p < 0.05). Clarithromycin and quinolone resistance rates in first-line were 24% and 8.3%, respectively. The overall adverse events' incidence rate was 13.4%, and therapy compliance was 97%. Conclusions: Considering the high eradication rate, 14-day non-bismuth quadruple concomitant therapy is a reasonable first-line choice, while quinolone-based therapy and single-capsule Pylera® should be considered as rescue therapy options. [ABSTRACT FROM AUTHOR]

Alternative therapies and vaccination are essential to combat the emergence of multidrug-resistant Helicobacter pylori and to prevent the development of gastroduodenal diseases. This review aimed to systematically review recent studies on alternative therapies, i.e., probiotics, nanoparticles, and natural products from plants, as well as recent progress in H. pylori vaccines at the preclinical stage. Articles published from January 2018 to August 2022 were systematically searched using PubMed, Scopus, Web of Science, and Medline. After the screening process, 45 articles were eligible for inclusion in this review. Probiotics (n = 9 studies) and natural products from plants (n = 28 studies) were observed to inhibit the growth of H. pylori, improve immune response, reduce inflammation, and reduce the pathogenic effects of H. pylori virulence factors. Natural products from plants also showed anti-biofilm activity against H. pylori. However, clinical trials of natural products from plants and probiotics are still lacking. A paucity of data assessing the nanoparticle activity of N-acylhomoserine lactonase-stabilized silver against H. pylori was observed. Nonetheless, one nanoparticle study showed anti-biofilm activity against H. pylori. Promising results of H. pylori vaccine candidates (n = 7) were observed at preclinical stage, including elicitation of a humoral and mucosal immune response. Furthermore, the application of new vaccine technology including multi-epitope and vector-based vaccines using bacteria was investigated at the preclinical stage. Taken together, probiotics, natural products from plants, and nanoparticles exhibited antibacterial activity against H. pylori. New vaccine technology shows promising results against H. pylori. [ABSTRACT FROM AUTHOR]