scholarly journals Helicobacter pylori treatment in the post-antibiotics era—searching for new drug targets

2020 ◽  
Vol 104 (23) ◽  
pp. 9891-9905 ◽  
Author(s):  
Paula Roszczenko-Jasińska ◽  
Marta Ilona Wojtyś ◽  
Elżbieta K. Jagusztyn-Krynicka
Keyword(s):  
Helicobacter Pylori ◽  
Drug Targets ◽  
Recent Effort ◽  
Antibiotic Resistant ◽  
New Drug ◽  
Group I ◽  
Key Points ◽  
New Antibiotics ◽  
Helicobacter Pylori Treatment ◽  
H Pylori

Abstract Helicobacter pylori, a member of Epsilonproteobacteria, is a Gram-negative microaerophilic bacterium that colonizes gastric mucosa of about 50% of the human population. Although most infections caused by H. pylori are asymptomatic, the microorganism is strongly associated with serious diseases of the upper gastrointestinal tract such as chronic gastritis, peptic ulcer, duodenal ulcer, and gastric cancer, and it is classified as a group I carcinogen. The prevalence of H. pylori infections varies worldwide. The H. pylori genotype, host gene polymorphisms, and environmental factors determine the type of induced disease. Currently, the most common therapy to treat H. pylori is the first line clarithromycin–based triple therapy or a quadruple therapy replacing clarithromycin with new antibiotics. Despite the enormous recent effort to introduce new therapeutic regimens to combat this pathogen, treatment for H. pylori still fails in more than 20% of patients, mainly due to the increased prevalence of antibiotic resistant strains. In this review we present recent progress aimed at designing new anti-H. pylori strategies to combat this pathogen. Some novel therapeutic regimens will potentially be used as an extra constituent of antibiotic therapy, and others may replace current antibiotic treatments. Key points • Attempts to improve eradication rate of H. pylori infection. • Searching for new drug targets in anti-Helicobacter therapies.

scholarly journals Correlation between Quantitative 13C-Urea Breath Test and Helicobacter pylori Treatment Success in a Population-Based Cohort

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Doron Boltin ◽  
Zohar Levi ◽  
Tsachi Tsadok Perets ◽  
Hemda Schmilovitz-Weiss ◽  
Rachel Gingold-Belfer ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Breath Test ◽  
Treatment Success ◽  
Population Based ◽  
Urea Breath Test ◽  
First Line Therapy ◽  
13C Urea Breath Test ◽  
Helicobacter Pylori Treatment ◽  
H Pylori ◽  
First Time

Background. There are continual efforts to identify factors which influence the success of first-line therapy for Helicobacter pylori (H. pylori) infection. The 13C-urea breath test result (C13-UBT) utilizes H. pylori urease activity and is a highly accurate diagnostic assay. We aimed to determine whether the magnitude of C13-UBT result is related to treatment success. Methods. Adult patients who underwent a first-time 13C-urea breath test between January 2010 and January 2016 were included. In order to isolate a naïve test-and-treat population who were unlikely to have undergone an initial endoscopy-based H. pylori test, we excluded patients > 45 years and those with a previous C13-UBT. Data were extracted from the Clalit Health Services laboratory database. Results. A total of 94,590 subjects (36.1% male, age 28.5 ± 6.0 years) who underwent a first-time C13-UBT during the study period were included. C13-UBT was positive in 48,509 (51.3%) subjects. A confirmatory posttreatment C13-UBT was performed in 18,375 (37.8%), and eradication was successful in 12,018 (65.4%). The mean C13-UBT recording was 20.6 ± 16.2 DOB in subjects with successful eradication and 19.5 ± 13.1 DOB in subjects with treatment failure (OR, 1.01; 95% CI 1.00-1.01, p<0.01). Among patients in the upper quintile of C13-UBT measurement, eradication was achieved in 67.6%, compared to 62.6% in the lower quintile (OR, 1.22; 95% CI 1.11-1.35, p<0.01). Subjects in the top 1 percentile (C13-UBT ≥ 70 DOB) achieved eradication in 75.0%, compared to 65.3% among subjects with C13-UBT < 70 DOB (OR, 1.59; 95% CI 1.05-2.41, p<0.01). Conclusions. The superiority in H. pylori eradication observed in subjects with a higher C13-UBT DOB is small but significant. Further studies should examine the physiological and microbiological basis for this finding.

scholarly journals Helicobacter pylori eradication using tetracycline and furazolidone versus amoxicillin and azithromycin in lansoprazole based triple therapy: an open randomized clinical trial

2005 ◽  
Vol 42 (2) ◽  
pp. 111-115 ◽  
Author(s):  
Laura Cidrão Frota ◽  
Maria do Perpétuo Socorro Saldanha da Cunha ◽  
Carlos René Lima Luz ◽  
Antonio Haroldo de Araujo-Filho ◽  
Luciano A. S. Frota ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Triple Therapy ◽  
Protocol Analysis ◽  
Urea Breath Test ◽  
Test Results ◽  
Suitable Alternative ◽  
Helicobacter Pylori Eradication ◽  
Helicobacter Pylori Treatment ◽  
H Pylori ◽  
To Receive

BACKGROUND: Optimal anti-Helicobacter pylori treatment has not yet been established. AIM: To evaluate H. pylori eradication using tetracycline and furazolidone versus amoxicillin and azithromycin in lansoprazole based triple therapy in northeastern of Brazil. PATIENTS AND METHODS: One hundred and four patients with H. pylori infection, as determined by rapid urease testing and histology, were randomly assigned to receive either: lansoprazole (30 mg q.d.), tetracycline (500 mg q.i.d.), and furazolidone (200 mg t.i.d.) for 7 days (LTF; n = 52); or lansoprazole (30 mg b.i.d.) and amoxicillin (1 g b.i.d.) for 1 week, plus azithromycin (500 mg q.d.) for the first 3 days (LAAz; n = 52). H. pylori eradication was assessed 3 months following completion of therapy by means of rapid urease testing, histology and a 14C-urea breath test. RESULTS: H. pylori eradication was achieved in 46 of 52 (88.4%, 95% CI: 77.5%-95.1%) patients in LTF group and in 14 of 52 (26.9%, 95% CI: 16.2%-40,1%) patients in LAAz group. On a per-protocol analysis, eradication rates were 91.8% (95% CI: 81.4%-97.3%) and 28.5% (95% CI: 17.2%-42.3%), respectively in LTF and LAAz groups. CONCLUSION: The LAAz regimen yielded unacceptably low eradication rates. On the other hand, the LTF scheme represents a suitable alternative for H. pylori eradication.

scholarly journals Can probiotics improve efficiency and safety profile of triple Helicobacter pylori eradication therapy? A prospective randomized study

2016 ◽  
Vol 73 (11) ◽  
pp. 1044-1049 ◽  
Author(s):  
Sasa Grgov ◽  
Tomislav Tasic ◽  
Biljana Radovanovic-Dinic ◽  
Daniela Benedeto-Stojanov
Keyword(s):  
Helicobacter Pylori ◽  
Randomized Study ◽  
Eradication Therapy ◽  
Saccharomyces Boulardii ◽  
Rapid Urease Test ◽  
Group I ◽  
Urease Test ◽  
Probiotic Strains ◽  
The Difference ◽  
H Pylori

Background/Aim. Some studies suggest the benefit of applying different probiotic strains in combination with antibiotics in the eradication of Helicobacter pylori (H. pylori) infection. The aim of this study was to evaluate the effect of co-administration of multiple probiotic strains with triple H. pylori eradication therapy. Methods. This prospective study included 167 patients with dyspeptic symptoms and chronic gastritis who were diagnosed with H. pylori infection and randomized into two groups. The group I of 77 patients underwent triple eradication therapy, for 7 days, with lansoprazole, 2 ? 30 mg half an hour before the meal, amoxicillin 2 ? 1.000 mg per 12 hours and clarithromycin 2 ? 500 mg per 12 hours. After the 7th day of the therapy, lansoprazole continued at a dose of 30 mg for half an hour before breakfast for 4 weeks. The group II of 90 patients received the same treatment as the patients of the group I, with the addition of the probiotic cultures in the form of a capsule comprising Lactobacillus Rosell-52, Lactobacillus Rosell-11, Bifidobacterium Rosell-1755 and Saccharomyces boulardii, since the beginning of eradication for 4 weeks. Eradication of H. pylori infection control was performed 8 weeks after the therapy by rapid urease test and histopathologic evaluation of endoscopic biopsies or by stool antigen test for H. pylori. Results. Eradication of H. pylori infection was achieved in 93.3% of the patients who received probiotics with eradication therapy and in 81.8% of patients who were only on eradication therapy without probiotics. The difference in eradication success was statistically significant, (p < 0.05). The incidence of adverse effects of eradication therapy was higher in the group of patients who were not on probiotic (28.6%) than in the group that received probiotic (17.7%), but the difference was not statistically significant. Conclusion. Multiple probiotic strains addition to triple eradication therapy of H. pylori achieves a significantly better eradication success, with fewer side effects of antibiotics.

scholarly journals Are Synbiotics added to the Standard Therapy to eradicate Helicobacter pylori in Children Beneficial? A Randomized Controlled Study

2017 ◽  
Vol 7 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Banu N Şirvan ◽  
Merve K Usta ◽  
Nuray U Kızılkan ◽  
Nafiye Urgancı
Keyword(s):  
Helicobacter Pylori ◽  
Abdominal Pain ◽  
Triple Therapy ◽  
Standard Therapy ◽  
Randomized Controlled Study ◽  
Controlled Study ◽  
Randomized Controlled ◽  
Group I ◽  
Dyspeptic Symptoms ◽  
H Pylori

ABSTRACT Aim We aimed to evaluate the role of the addition of Bifidobacterium lactis-containing synbiotic to the triple therapy in the case of Helicobacter pylori eradication, the dyspeptic symptoms, and reducing the side effects of antibiotics. Materials and methods A total of 104 children aged between 5 and 17 years, who were histopathologically diagnosed with H. pylori were enrolled in this study, of whom 100 were included in the analysis. Patients were randomly classified into two groups. In the first group, 50 patients were administered amoxicillin + clarithromycin + lansoprazole for 14 days and B. lactis-containing synbiotic. In the second group, 50 patients were treated with the standard triple therapy. All patients were given information after completion of therapy. Results H. pylori eradication was achieved in 88% in group I who received standard therapy with additional synbiotic and 72% in group II (p = 0.046). The number of patients in the second group who suffered from abdominal pain between the 3rd and 14th day of the treatment was higher (p < 0.05). The addition of probiotics to the triple therapy significantly reduced the frequency of diarrhea, but no significant difference was detected in the frequency of metallic taste (p = 0.04, p = 0.418 respectively). Conclusion The addition of synbiotic to the triple therapy is effective for eradicating H. pylori infection in children and is usually helpful to reduce or eliminate dyspeptic symptoms like abdominal pain, diarrhea, and vomiting. This study suggest that improved tolerance to the eradication treatment also reduces the treatment failure by adding probiotics and encourages the future study using probiotic supplementation in H. pylori treatment. How to cite this article Şirvan BN, Usta MK, Kızılkan NU, Urgancı N. Are Synbiotics added to the Standard Therapy to eradicate Helicobacter Pylori in Children Beneficial? A Randomized Controlled Study. Euroasian J Hepato-Gastroenterol 2017;7(1):17-22.

scholarly journals Prediction of Epitopes in the Proteome of Helicobacter pylori

2018 ◽  
Vol 10 (7) ◽  
pp. 148 ◽  
Author(s):  
Elkin Navarro-Quiroz ◽  
Roberto Navarro-Quiroz ◽  
Pierine España-Puccini ◽  
José Luis Villarreal ◽  
Anderson Díaz Perez ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
World Health ◽  
Phase Variable ◽  
Human Pathogens ◽  
Web Tool ◽  
Group I ◽  
Increased Risk ◽  
Risk Of Disease ◽  
H Pylori ◽  
Health Organization

Helicobacter pylori (H. pylori) is classified by the World Health Organization (WHO) as a group I carcinogen and is one of the most efficient human pathogens with over half of the world's population colonized by this gram-negative spiral bacterium. H. pylori can cause a chronic infection in the stomach during early childhood that persists throughout life due to diverse mechanisms of immune response evasion. H. pylori has several factors strongly associated with increased risk of disease such as toxins, adhesins, and chemoattractants, some of which are highly polymorphic, phase variable, and have different functions. Conventional treatments involve the use of antibiotics. However, treatment frequently fails due to the resistance H. pylori has progressively developed to antibiotics. This creates the need for different treatments made possible by identifying new therapeutic targets in the pathogen’s genome.The purpose of this study was an in silico prediction of T- and B- epitopes in H. pylori proteins. Twenty-two external membrane proteins from H. pylori Strain 26695 (accession number NC_000915) were identified using the web tool Vaxign (http://www.violinet.org/vaxign/). A total of one-hundred epitopes (60 class I epitopes and 40 class II epitopes) that could be used to develop novel non-antibiotics drugs for an H. pylori infection were predicted.

scholarly journals Epidemiology of the Antibiotic Resistance ofHelicobacter pyloriin Canada

2000 ◽  
Vol 14 (10) ◽  
pp. 879-882 ◽  
Author(s):  
Carlo A Fallone
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Digestive Disease ◽  
Study Group ◽  
Cure Rate ◽  
Antibiotic Resistant ◽  
Treatment Regimens ◽  
Metronidazole Resistance ◽  
American Gastroenterology Association ◽  
H Pylori

BACKGROUND: The rate ofHelicobacter pyloriresistance to antibiotics determines the cure rate of treatment regimens containing such antibiotics. AIMS: To review the literature to determine the rates ofH pyloriresistance to metronidazole and clarithromycin in Canada, and whether these rates vary in different regions of Canada.METHODS: The literature was reviewed extensively for the prevalence of antibiotic-resistantH pyloriin Canada by searching MEDLINE from January 1980 to May 1999, as well as abstracts of the American Gastroenterology Association Digestive Disease Week, Canadian Digestive Disease Week and The EuropeanH pyloriStudy Group Meetings from January 1995 to May 1999.RESULTS: Eleven studies that estimatedH pyloriresistance to metronidazole resistance and nine that estimated resistance to clarithromycin in Canada were identified. Rates of resistance for metronidazole and clarithromycin varied from 11% to 48% and 0% to 12%, respectively. Studies that obtained their estimates using the E-test and those that did not clearly exclude patients who had undergone previous attempts atH pylorieradication had higher estimates of resistance, accounting for this variability in results.CONCLUSIONS: The prevalence of primaryH pyloriresistance in Canada appears to be 18% to 22% for metronidazole and less than 4% for clarithromycin. These rates appear to be consistent across the different regions studied in Canada, but many regions have not been studied.

scholarly journals Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sabine Bernegger ◽  
Robert Vidmar ◽  
Marko Fonovic ◽  
Gernot Posselt ◽  
Boris Turk ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Intercellular Junctions ◽  
Matrix Metalloproteases ◽  
Proteomic Profiling ◽  
Proteomic Approach ◽  
Group I ◽  
H Pylori ◽  
Intercellular Adhesions

Abstract Background High temperature requirement A (HtrA) is an active serine protease secreted by the group-I carcinogen Helicobacter pylori (H. pylori). The human cell adhesion protein and tumor suppressor E-cadherin (hCdh1) expressed on the surface of gastric epithelial cells was identified as the first HtrA substrate. HtrA-mediated hCdh1 cleavage and subsequent disruption of intercellular adhesions are considered as important steps in H. pylori pathogenesis. In this study, we performed a proteomic profiling of H. pylori HtrA (HpHtrA) to decipher the complex mechanism of H. pylori interference with the epithelial barrier integrity. Results Using a proteomic approach we identified human desmoglein-2 (hDsg2), neuropilin-1, ephrin-B2, and semaphorin-4D as novel extracellular HpHtrA substrates and confirmed the well characterized target hCdh1. HpHtrA-mediated hDsg2 cleavage was further analyzed by in vitro cleavage assays using recombinant proteins. In infection experiments, we demonstrated hDsg2 shedding from H. pylori-colonized MKN28 and NCI-N87 cells independently of pathogen-induced matrix-metalloproteases or ADAM10 and ADAM17. Conclusions Characterizing the substrate specificity of HpHtrA revealed efficient hDsg2 cleavage underlining the importance of HpHtrA in opening intercellular junctions.

cagA-Positive Helicobacter pylori Populations in China and The Netherlands Are Distinct

1998 ◽  
Vol 66 (5) ◽  
pp. 1822-1826 ◽  
Author(s):  
Arie van der Ende ◽  
Zhi-Jun Pan ◽  
Aldert Bart ◽  
René W. M. van der Hulst ◽  
Monique Feller ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
The Netherlands ◽  
Random Amplified Polymorphic Dna ◽  
Chromosomal Dna ◽  
High Confidence ◽  
Protein Levels ◽  
Group I ◽  
Rapd Pcr ◽  
H Pylori ◽  
Chinese Group

ABSTRACT The aim of this research was to study whether and to what extent Chinese cagA-positive Helicobacter pyloriisolates differ from those in The Netherlands. Analysis of random amplified polymorphic DNA (RAPD)-PCR-assessed DNA fingerprints of chromosomal DNA of 24 cagA-positive H. pylori isolates from Dutch (n = 12) and Chinese (n = 10) patients yielded the absence of clustering. Based on comparison of the sequence of a 243-nucleotide part ofcagA, the Dutch (group I) and Chinese (group II)H. pylori isolates formed two separate branches with high confidence limits in the phylogenetic tree. These two clusters were not observed when the sequence of a 240-bp part ofglmM was used in the comparison. The number of nonsynonymous substitutions was much higher in cagA than inglmM, indicating positive selection. The average levels of divergence of cagA at the nucleotide and protein levels between group I and II isolates were found to be high, 13.3 and 17.9%, respectively. Possibly, the pathogenicity island (PAI) that has been integrated into the chromosome of the ancestor of H. pylori now circulating in China contained a differentcagA than the PAI that has been integrated into the chromosome of the ancestor of H. pylori now circulating in The Netherlands. We conclude that in China and The Netherlands, two distinct cagA-positive H. pylori populations are circulating.

scholarly journals Identification of Potential Drug Targets in Helicobacter pylori Using In Silico Subtractive Proteomics Approaches and Their Possible Inhibition through Drug Repurposing

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 747 ◽  
Author(s):  
Kareem A. Ibrahim ◽  
Omneya M. Helmy ◽  
Mona T. Kashef ◽  
Tharwat R. Elkhamissy ◽  
Mohammed A. Ramadan
Keyword(s):  
Helicobacter Pylori ◽  
Drug Targets ◽  
Cellular Localization ◽  
Drug Repurposing ◽  
World Health ◽  
Potential Drug ◽  
Protein Pool ◽  
Subtractive Proteomics ◽  
H Pylori ◽  
Potential Drug Targets

The class 1 carcinogen, Helicobacter pylori, is one of the World Health Organization’s high priority pathogens for antimicrobial development. We used three subtractive proteomics approaches using protein pools retrieved from: chokepoint reactions in the BIOCYC database, the Kyoto Encyclopedia of Genes and Genomes, and the database of essential genes (DEG), to find putative drug targets and their inhibition by drug repurposing. The subtractive channels included non-homology to human proteome, essentiality analysis, sub-cellular localization prediction, conservation, lack of similarity to gut flora, druggability, and broad-spectrum activity. The minimum inhibitory concentration (MIC) of three selected ligands was determined to confirm anti-helicobacter activity. Seventeen protein targets were retrieved. They are involved in motility, cell wall biosynthesis, processing of environmental and genetic information, and synthesis and metabolism of secondary metabolites, amino acids, vitamins, and cofactors. The DEG protein pool approach was superior, as it retrieved all drug targets identified by the other two approaches. Binding ligands (n = 42) were mostly small non-antibiotic compounds. Citric, dipicolinic, and pyrophosphoric acid inhibited H. pylori at an MIC of 1.5–2.5 mg/mL. In conclusion, we identified potential drug targets in H. pylori, and repurposed their binding ligands as possible anti-helicobacter agents, saving time and effort required for the development of new antimicrobial compounds.

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