Helicobacter pylori Infection - New Data and Approaches on Diagnosis, Pathogenesis, Antibiotic Resistance and Advances in Therapy

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 August 2024) | Viewed by 24747

Special Issue Editor


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Guest Editor
Department of Medical Microbiology, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria
Interests: Helicobacter pylori; anaerobes; diagnostic methods; virulence; antibiotic resistance; multidrug resistance; probiotics

Special Issue Information

Dear Colleagues,

Helicobacter pylori is one of the most common causative agents of chronic infections and affects 20–50% of people in different countries, being included by the World Health Organization in the group of strongest carcinogens. In addition to the main markers of virulence—the pathogenicity island cagPAI, cagA gene, and vacA mosaicism—H. pylori can display a plethora of other virulence factors as well. Infection is linked to the development of chronic gastritis, peptic ulcers, and tumors such as gastric carcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. Infection is still very common in adults and also in children in many countries and carries a lifetime risk of serious gastroduodenal diseases. It is also associated with some extra-gastric diseases. Constant efforts are needed to optimize the diagnosis of infection, to evaluate H. pylori pathogenesis and virulence factors in depth, as well as to improve therapeutic success. Regimens with two or three antibiotics, a proton pump inhibitor, and sometimes with addition of a bismuth preparation have been used for eradication of the infection; however, antibiotic resistance has been increasing and is the major cause of eradication failure. Moreover, some strains are multidrug-resistant. However, new promising agents and approaches have been evaluated. Improvement or application of new methods, agents and regimens for diagnostics, research and therapeutic purposes are of paramount importance to control the frequent, chronic, and potentially carcinogenic H. pylori infection in humans.

Prof. Dr. Lyudmila Boyanova
Guest Editor

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Keywords

  • Helicobacter pylori
  • H. pylori infection in childhood
  • pathogenesis
  • virulence factors
  • antibiotic resistance
  • eradication regimens
  • new diagnostic tools
  • new treatment agents

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Published Papers (8 papers)

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Research

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11 pages, 2304 KiB  
Article
Trends in Upper Gastrointestinal Bleeding in Children: The Impact of Helicobacter pylori Infection and Non-Steroidal Anti-Inflammatory Drug Use
by Felicia Galos, Mara Ioana Ionescu, Mihai Daniel Luca Mirea, Anca Andreea Boboc, Andreea Ioan and Catalin Boboc
Antibiotics 2024, 13(8), 752; https://doi.org/10.3390/antibiotics13080752 - 10 Aug 2024
Cited by 1 | Viewed by 1015
Abstract
Upper gastrointestinal bleeding (UGIB) is a significant concern in children, contributing to 6–20% of cases in pediatric intensive care units. This study evaluates the roles of Helicobacter pylori (H. pylori) infection and non-steroidal anti-inflammatory drug (NSAID) usage in the etiology of [...] Read more.
Upper gastrointestinal bleeding (UGIB) is a significant concern in children, contributing to 6–20% of cases in pediatric intensive care units. This study evaluates the roles of Helicobacter pylori (H. pylori) infection and non-steroidal anti-inflammatory drug (NSAID) usage in the etiology of UGIB in children, with a particular focus on trends observed during the COVID-19 pandemic. We conducted a retrospective analysis of 103 pediatric patients who underwent esophagogastroduodenoscopy (EGD) for UGIB between January 2015 and December 2023. Of these, 88 patients were included in the final analysis, where the source of bleeding was successfully identified. Hematemesis was the most common presentation, and the source of bleeding was identified in 85.43% of cases. The prevalence of H. pylori infection remained stable across the pre-pandemic (39.7%) and post-pandemic (36.7%) periods. However, NSAID usage increased nearly threefold during the pandemic, with 36.7% of post-pandemic UGIB cases associated with NSAID use, compared to 12.1% pre-pandemic. These findings underscore the significant roles of H. pylori and NSAID use in pediatric UGIB, with a notable increase in NSAID-related cases during the pandemic. Full article
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15 pages, 836 KiB  
Article
Antibiotic Resistance in Helicobacter pylori Isolates from Northwestern and Central Romania Detected by Culture-Based and PCR-Based Methods
by Carmen Costache, Horațiu Alexandru Colosi, Simona Grad, Anamaria Ioana Paștiu, Mariela Militaru, Anca Paula Hădărean, Dan Alexandru Țoc, Vlad Sever Neculicioiu, Alina Mihaela Baciu, Razvan Vlad Opris, Dan Lucian Dumitrașcu and Ioana Alina Colosi
Antibiotics 2023, 12(12), 1672; https://doi.org/10.3390/antibiotics12121672 - 28 Nov 2023
Cited by 3 | Viewed by 1610
Abstract
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 [...] Read more.
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. Full article
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Review

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14 pages, 285 KiB  
Review
Current and Future Perspectives on the Management of Helicobacter pylori: A Narrative Review
by Charlene Deane, Orlaith Kelly and Colm O’Morain
Antibiotics 2024, 13(6), 541; https://doi.org/10.3390/antibiotics13060541 - 10 Jun 2024
Cited by 1 | Viewed by 2556
Abstract
The prevalence of Helicobacter pylori (H. pylori), a pathogen, has decreased globally in the last decade. To date, the management of H. pylori has focused on a reactive approach, whereby those diagnosed are treated with antimicrobials and acid suppression in combination. This [...] Read more.
The prevalence of Helicobacter pylori (H. pylori), a pathogen, has decreased globally in the last decade. To date, the management of H. pylori has focused on a reactive approach, whereby those diagnosed are treated with antimicrobials and acid suppression in combination. This review article provides an overview of the shift in the management of H. pylori from a reactive approach towards a proactive ‘screen and treat’ approach; the article reflects the current pharmacological landscape for H. pylori treatment by exploring similarities such as the first-line prescription of quadruple therapy in most countries and provides a summary table of the best practice guidance from Europe, Asia, and North America. It explores significant ongoing challenges in management, such as rising antimicrobial resistance rates, and explores a potential ‘work smart’ approach to antimicrobial susceptibility testing. We explore the role of registry databases in providing data on treatment efficacy and safety and how they can support a strategic approach to H. pylori treatment. We question if such a database’s availability, update, and regular audit should serve as a key quality indicator in a population screening programme. Despite a call for vaccination against H. pylori and decades of research, not many have made it to a phase-three clinical trial. We explore the challenges that have complicated the development of such a vaccine, such as the genetic diversity of H. pylori, immunotolerance, and limitations of mouse models in research; we reflect on how these challenges are contributing to a low likelihood of having a vaccine in the short–medium term. Lastly, it explores the heterogeneity in research on probiotics and their role as an adjunct in the management of H. pylori. Full article
16 pages, 335 KiB  
Review
Helicobacter pylori Infections in Children
by Julie Nguyen, Kallirroi Kotilea, Patrick Bontems and Veronique Yvette Miendje Deyi
Antibiotics 2023, 12(9), 1440; https://doi.org/10.3390/antibiotics12091440 - 12 Sep 2023
Cited by 7 | Viewed by 2902
Abstract
In the context of epidemiology, host response, disease presentation, diagnosis, and treatment management, the manifestation of Helicobacter pylori (H. pylori) infection diverges between children and adults. H. pylori infection stands out as one of the most prevalent bacterial infections globally, and [...] Read more.
In the context of epidemiology, host response, disease presentation, diagnosis, and treatment management, the manifestation of Helicobacter pylori (H. pylori) infection diverges between children and adults. H. pylori infection stands out as one of the most prevalent bacterial infections globally, and its prevalence in both children and adults is decreasing in many developing countries but some still struggle with a high prevalence of pediatric H. pylori infection and its consequences. The majority of infected children are asymptomatic and pediatric studies do not support the involvement of H. pylori in functional disorders such as recurrent abdominal pain. The pathophysiology of H. pylori infection relies on complex bacterial virulence mechanisms and their interaction with the host immune system and environmental factors. This interaction gives rise to diverse gastritis phenotypes, which subsequently influence the potential development of various gastroduodenal pathologies. In clinical settings, the diagnosis of this infection in childhood requires an upper gastrointestinal endoscopic exam with mucosal biopsy samples for histology and culture, or Polymerase Chain Reaction (PCR) at the very least. When warranted, eradication treatment should be given when good compliance is expected, and there should be systematic use of a treatment adapted to the antimicrobial susceptibility profile. To combat the burgeoning threat of multidrug resistance, vigilant surveillance of resistance patterns and strategic antibiotic management are paramount. Full article
10 pages, 276 KiB  
Review
Epidemiology of Helicobacter pylori Resistance to Antibiotics (A Narrative Review)
by Irena Mladenova
Antibiotics 2023, 12(7), 1184; https://doi.org/10.3390/antibiotics12071184 - 13 Jul 2023
Cited by 13 | Viewed by 3230
Abstract
Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide and one of the main etiological factors of chronic gastritis, peptic ulcer disease, and stomach neoplasms. The mass application of antibiotics without testing, especially during the last years of the [...] Read more.
Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide and one of the main etiological factors of chronic gastritis, peptic ulcer disease, and stomach neoplasms. The mass application of antibiotics without testing, especially during the last years of the pandemic of SARS-CoV-2, could lead to a dramatic increase in antibiotic resistance and reduced effectiveness of eradication regimens for H. pylori infection. The epidemiology of H. pylori resistance to antibiotics still has unclear mechanisms. Antibiotic policy should be intensified to optimize treatment, and regular monitoring of resistance of H. pylori in different geographical regions should be conducted. Individualized treatment according to susceptibility testing is strongly advisable, and the best treatment regimens should be selected. The mutations in the genes encoding the antibiotic target protein are significant risk factors for H. pylori resistance. Iatrogenic errors in diagnosis and prescribing treatment for the failure of H. pylori eradication are other important risk factors. The low level of awareness and compliance with the correct treatment influence the rate of H. pylori resistance. Epidemiological surveillance of antibiotic resistance and the adoption of new treatment strategies are needed. The discovery of an efficient vaccine against H. pylori could reduce the pressure of the world’s growing antibiotic resistance. Full article
18 pages, 378 KiB  
Review
Newer, Older, and Alternative Agents for the Eradication of Helicobacter pylori Infection: A Narrative Review
by György Miklós Buzás and Péter Birinyi
Antibiotics 2023, 12(6), 946; https://doi.org/10.3390/antibiotics12060946 - 23 May 2023
Cited by 12 | Viewed by 3038
Abstract
Although discovered 40 years ago, Helicobacter pylori infection is still raising diagnostic and therapeutic problems today. The infection is currently managed based on statements in several guidelines, but implementing them in practice is a long process. Increasing antibiotic resistance and weak compliance of [...] Read more.
Although discovered 40 years ago, Helicobacter pylori infection is still raising diagnostic and therapeutic problems today. The infection is currently managed based on statements in several guidelines, but implementing them in practice is a long process. Increasing antibiotic resistance and weak compliance of the patients limit the efficacy of eradication regimens, leaving much room for improvement. Third-generation proton pump inhibitors have added little to the results of the first two generations. Potassium-competitive acid blockers have a stronger and longer inhibitory action of acid secretion, increasing the intragastric pH. They obtained superior results in eradication when compared to proton pump inhibitors. Instead of innovative antibiotics, derivatives of existing antimicrobials were developed; some new fluoroquinolones and nitazoxanide seem promising in practice, but they are not recommended by the guidelines. Carbonic anhydrase inhibitors have both anti-secretory and bactericidal effects, and some researchers are expecting their revival in the treatment of infection. Capsules containing components of the eradication regimens have obtained excellent results, but are of limited availability. Probiotics, if containing bacteria with anti-Helicobacter pylori activity, may be useful, increasing the rates of eradication and lowering the prevalence and severity of the side effects. Full article
19 pages, 922 KiB  
Review
Evolution of Helicobacter pylori Resistance to Antibiotics: A Topic of Increasing Concern
by Lyudmila Boyanova, Petyo Hadzhiyski, Raina Gergova and Rumyana Markovska
Antibiotics 2023, 12(2), 332; https://doi.org/10.3390/antibiotics12020332 - 4 Feb 2023
Cited by 54 | Viewed by 5924
Abstract
Antibiotic resistance among Helicobacter pylori strains is the major cause of eradication failure. Resistance prevalence is dynamic and can greatly vary among countries over the years. We revealed H. pylori resistance trends for five antibiotics in 14 countries through articles predominantly published in [...] Read more.
Antibiotic resistance among Helicobacter pylori strains is the major cause of eradication failure. Resistance prevalence is dynamic and can greatly vary among countries over the years. We revealed H. pylori resistance trends for five antibiotics in 14 countries through articles predominantly published in 2018–2022, since the latest data can best show the most recent trends in resistance evolution. Amoxicillin resistance generally exhibited no evolution, yet it increased in Bulgaria, Iran, China, and Vietnam. Metronidazole resistance exhibited different trends, including an increase, a decrease and no evolution in six, three, and five studies, respectively. Clarithromycin resistance increased in Australia, Belgium, Bulgaria, Italy, Iran, and Taiwan, but remained stable in France, Spain, Russia, China, Chile, and Colombia. Tetracycline resistance was low and stable except in Iran. Levofloxacin resistance increased in four European and six other countries/regions, without significant increases in France, Spain, and Chile. In Chile, triple resistance also increased. In countries such as France and Spain, resistance to most antibiotics was stabilized, while in Bulgaria, Belgium, Iran and Taiwan, resistance to three or more agents was reported. Use of non-recommended regimens, national antibiotic consumption, patient’s compliance, host factors, strain virulence, migrations, and azithromycin overuse during the COVID-19 pandemic can influence resistance evolution. New drugs, eradication regimens and diagnostic methods, such as next-generation sequencing can improve H. pylori infection control. Full article
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Other

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10 pages, 289 KiB  
Perspective
Whole Genome Sequencing for Studying Helicobacter pylori Antimicrobial Resistance
by Belén Fernández-Caso, Ana Miqueleiz and Teresa Alarcón
Antibiotics 2023, 12(7), 1135; https://doi.org/10.3390/antibiotics12071135 - 30 Jun 2023
Cited by 9 | Viewed by 2994
Abstract
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 [...] Read more.
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. Full article
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