scholarly journals Small Molecule Inhibitors of the Response Regulator ArsR Exhibit Bactericidal Activity against Helicobacter pylori

2020 ◽  
Vol 8 (4) ◽  
pp. 503 ◽  
Author(s):  
Andrés González ◽  
Javier Casado ◽  
Eduardo Chueca ◽  
Sandra Salillas ◽  
Adrián Velázquez-Campoy ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
High Throughput Screening ◽  
Lithocholic Acid ◽  
Response Regulator ◽  
Bacterial Pathogen ◽  
Antimicrobial Effect ◽  
Chemical Library ◽  
Secondary Bile Acid ◽  
H Pylori

Helicobacter pylori is considered the most prevalent bacterial pathogen in humans. The increasing antibiotic resistance evolved by this microorganism has raised alarm bells worldwide due to the significant reduction in the eradication rates of traditional standard therapies. A major challenge in this antibiotic resistance crisis is the identification of novel microbial targets whose inhibitors can overcome the currently circulating resistome. In the present study, we have validated the use of the essential response regulator ArsR as a novel and promising therapeutic target against H. pylori infections. A high-throughput screening of a repurposing chemical library using a fluorescence-based thermal shift assay identified several ArsR binders. At least four of these low-molecular weight compounds noticeably inhibited the DNA binding activity of ArsR and showed bactericidal effects against antibiotic-resistant strains of H. pylori. Among the ArsR inhibitors, a human secondary bile acid, lithocholic acid, quickly destroyed H. pylori cells and exhibited partial synergistic action in combination with clarithromycin or levofloxacin, while the antimicrobial effect of this compound against representative members of the normal human microbiota such as Escherichia coli and Staphylococcus epidermidis appeared irrelevant. Our results enhance the battery of novel therapeutic tools against refractory infections caused by multidrug-resistant H. pylori strains.

Culture and Susceptibility of Levofloxacin Resistant H.pylori

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Sameh Mohamed Fahiem Ghaly ◽  
Hany Ali Hussien Abd El-Rahman ◽  
Mohamed Osama Aly Aly ◽  
Ahmed Medhat Youssef Ibrahim Youssef
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Proper Time ◽  
Wide Spectrum ◽  
Signs And Symptoms ◽  
Line Treatment ◽  
Clarithromycin Resistance ◽  
Prior Use ◽  
H Pylori ◽  
Main Factor

Abstract Background Antibiotic resistance in Helicobacter pylori is the major cause of eradication failure. Prevalence of H.pylori antibiotic resistance is increasing worldwide, and it is the main factor affecting efficacy of current therapeutic regimens. Our aim is to investigate H.pylori resistant patients toward Levofloxacin and detect the most effective antibiotic in eradication of H.pylori. Objective To investigate H.pylori resistant patients toward Levofloxacin including regimens and to detect the most effective antibiotic in H.pylori eradication. Patients and Methods The present study aimed to investigate the Susceptibility of Levofloxacin Resistant H.pylori in patients who had been diagnosed and received any regimen including Levofloxacin and still signs and symptoms of H.pylori infection not releaved and after proper time of stoppage of PPI and antibiotics H.pylori Ag in stool still positive at the period from January 2019 to February 2020. Results In the present study we found a wide spectrum of resistance to rates of H. pylori, from nearly negligible rates of Rifampicin (0%), Imipenem (0%), Cefotaxime (2%), Tetracycline (6%), Doxycycline(10%), and Amoxicillin(38%). To high rates resistance to Metronidazole (100%), Erythromycin (72%), Clarithromycin (68%), Azithromycin (60%), Ciprofloxacin (52%), and Levofloxacin (48%). Conclusion Helicobacter pylori is the most common chronic bacterial infection in humans. Antibiotic resistance is a major issue nowadays. Prior use of macrolide antibiotics or metronidazole appears to increase the risk of H. pylori resistance. Clarithromycin resistance appears to be an "absolute" condition that can not be overcome by increasing the macrolide dose. Levofloxacin resistance seems to be increasing. Culture and susceptibility should be done before starting second line treatment.

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

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1058
Author(s):  
Luis Bujanda ◽  
Olga P. Nyssen ◽  
Dino Vaira ◽  
Ilaria M. Saracino ◽  
Giulia Fiorini ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Antimicrobial Susceptibility ◽  
Susceptibility Testing ◽  
Resistance Rate ◽  
Antimicrobial Susceptibility Testing ◽  
Metronidazole Resistance ◽  
Infected Adult ◽  
H Pylori ◽  
European Registry

Background: Bacterial antibiotic resistance changes over time depending on multiple factors; therefore, it is essential to monitor the susceptibility trends to reduce the resistance impact on the effectiveness of various treatments. Objective: To conduct a time-trend analysis of Helicobacter pylori resistance to antibiotics in Europe. Methods: The international prospective European Registry on Helicobacter pylori Management (Hp-EuReg) collected data on all infected adult patients diagnosed with culture and antimicrobial susceptibility testing positive results that were registered at AEG-REDCap e-CRF until December 2020. Results: Overall, 41,562 patients were included in the Hp-EuReg. Culture and antimicrobial susceptibility testing were performed on gastric biopsies of 3974 (9.5%) patients, of whom 2852 (7%) were naive cases included for analysis. The number of positive cultures decreased by 35% from the period 2013–2016 to 2017–2020. Concerning naïve patients, no antibiotic resistance was found in 48% of the cases. The most frequent resistances were reported against metronidazole (30%), clarithromycin (25%), and levofloxacin (20%), whereas resistances to tetracycline and amoxicillin were below 1%. Dual and triple resistances were found in 13% and 6% of the cases, respectively. A decrease (p < 0.001) in the metronidazole resistance rate was observed between the 2013–2016 (33%) and 2017–2020 (24%) periods. Conclusion: Culture and antimicrobial susceptibility testing for Helicobacter pylori are scarcely performed (<10%) in Europe. In naïve patients, Helicobacter pylori resistance to clarithromycin remained above 15% throughout the period 2013–2020 and resistance to levofloxacin, as well as dual or triple resistances, were high. A progressive decrease in metronidazole resistance was observed.

scholarly journals Antibiotic Resistance of Helicobacter pylori Strains Isolated From Pediatric Patients in Southwest China

2021 ◽  
Vol 11 ◽  
Author(s):  
Juan Li ◽  
Jianjun Deng ◽  
Zhiling Wang ◽  
Hong Li ◽  
Chaomin Wan
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Pediatric Patients ◽  
Southwest China ◽  
Pediatric Population ◽  
Primary Resistance ◽  
Secondary Resistance ◽  
Treatment Naïve ◽  
H Pylori ◽  
Resistance Rates

The number of antibiotics that are appropriate for Helicobacter pylori eradication in children is limited. Profiling regional or population-specific antibiotic resistance is essential in guiding the H. pylori eradication treatment in children. The aim of this study was to evaluate the antibiotic resistance in H. pylori strains isolated from children and adolescents in Southwest China. Gastric biopsies from 157 pediatric patients with or without previous H. pylori eradication treatment were collected for H. pylori culture. Susceptibility to amoxicillin (AML), clarithromycin (CLR), metronidazole (MTZ), levofloxacin (LEV), tetracycline (TET), furazolidone (FZD), and rifampicin (RIF) was determined by E-test or a disk diffusion assay. A total of 87 patients from three ethnic groups (Han/Tibetan/Yi) were H. pylori culture positive (55.4%). The overall resistance rates were 55.2% for CLR, 71.3% for MTZ, 60.9% for RIF, and 18.4% for LEV. No isolate was found to be resistant to AML, TET, and FZD. Among the 53 treatment-naïve pediatric patients, primary resistance rates to clarithromycin, metronidazole, levofloxacin, and rifampicin were 45.3, 73.6, 15.1, and 60.4%, respectively. Among the 34 treatment-experienced patients, secondary resistance rates to clarithromycin, metronidazole, levofloxacin, and rifampicin were 70.6, 67.6, 23.5, and 61.8%, respectively. Isolates exhibiting simultaneous resistance to clarithromycin and metronidazole were 28.3 and 52.9% among the treatment-naïve and treatment-experienced patients, respectively. In conclusion, among pediatric patients in Southwest China, resistance rates were high for clarithromycin, metronidazole, levofloxacin, and rifampicin, whereas nil resistance was found to amoxicillin, tetracycline, and furazolidone. Our data suggest that the standard clarithromycin-based triple therapy should be abandoned as empiric therapy, whereas the bismuth quadruple therapy (bismuth/PPI/amoxicillin/tetracycline) would be suitable as first-line empiric treatment regimen for this pediatric population. Tetracycline and furazolidone may be considered for treating refractory H. pylori infections in adolescent patients.

scholarly journals Antibiotic resistance of Helicobacter pylori in the European part of the Russian Federation: first results

2020 ◽  
Vol 92 (8) ◽  
pp. 24-28
Author(s):  
I. V. Maev ◽  
D. N. Andreev ◽  
V. M. Govorun ◽  
E. N. Ilina ◽  
Yu. A. Kucheryavyy ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Russian Federation ◽  
European Part ◽  
Diffusion Method ◽  
Rapid Urease Test ◽  
Urease Test ◽  
First Results ◽  
The Russian Federation ◽  
H Pylori

Aim. Determine the primary antibiotic resistance of Helicobacter pylori (H. pylori) strains isolated from patients living in the European part of the Russian Federation. Materials and methods. As part of a clinical laboratory study, from 2015 to 2018, 27 gastrobiopsy samples obtained from H. pylori-infected patients were analyzed. H. pylori infection was verified using a rapid urease test or a 13C-urea breath test. The values of the minimum inhibitory concentration (MIC) of antibiotics were determined by the diffusion method using E-test strips (BioMerieux, France) according to the recommendations of the manufacturer. The sensitivity of the isolates was determined for 6 antibacterial drugs (amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, rifampicin). Results. According to the data obtained, resistance to amoxicillin was 0%, clarithromycin 11.1%, metronidazole 59.3%, levofloxacin 3.7%, tetracycline 0%, and rifampicin 14.8%. Dual resistance to clarithromycin and metronidazole was recorded in two isolates (7.4%). Conclusion. Thus, the first results of the evaluation of H. pylori antibiotic resistance in the European part of the Russian Federation indicate a low resistance of the microorganism to clarithromycin and quite high to metronidazole.

Primary antibiotic resistance of Helicobacter pylori among a Chinese Tibetan population

2020 ◽  
Vol 15 (14) ◽  
pp. 1353-1361
Author(s):  
Xiaoqiong Tang ◽  
Xiaohong Chen ◽  
Yalin Shen ◽  
Tiankuo Yang ◽  
Renwei Hu ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Primary Resistance ◽  
Tibetan Population ◽  
Disk Diffusion Assay ◽  
Treatment Naïve ◽  
Gastric Biopsies ◽  
H Pylori ◽  
Resistance Rates ◽  
Diffusion Assay

Aim: To evaluate the primary antibiotic resistance in Helicobacter pylori strains isolated from a Chinese Tibetan population. Methods & materials: Gastric biopsies from 400 H. pylori treatment-naive Tibetan patients were collected for H. pylori isolation. Susceptibility to amoxicillin (AML)/clarithromycin (CLR)/levofloxacin (LEV)/metronidazole (MTZ)/tetracycline (TET)/rifampicin (RIF)/furazolidone (FZD) was determined by E-test or a disk diffusion assay. Results: Biopsies from 117 patients were H. pylori culture positive (29.3%). The primary resistance rates to MTZ, CLR, LEV, RIF, AML, TET and FZD were 90.6, 44.4, 28.2, 69.2, 7.7, 0.8 and 0.8%, respectively. Interestingly, 42.7% of the strains had simultaneous resistance to CLR and MTZ. Conclusion: Among Tibetan strains, primary resistance rates were high for CLR/MTZ/LEV, whereas primary resistance rates to AML/TET/FZD were low. The high resistance to RIF is a concerning finding.

scholarly journals The role of the gastric bacterial microbiome in gastric cancer: Helicobacter pylori and beyond

2019 ◽  
Vol 12 ◽  
pp. 175628481989406 ◽  
Author(s):  
Christian Schulz ◽  
Kerstin Schütte ◽  
Julia Mayerle ◽  
Peter Malfertheiner
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Bacterial Pathogen ◽  
Gastric Carcinogenesis ◽  
Nucleotide Sequencing ◽  
Wide Field ◽  
Current State ◽  
Organ Systems ◽  
Bacterial Microbiome ◽  
H Pylori

A link between chronic inflammation and carcinogenesis has been depicted in many organ systems. Helicobacter pylori is the most prevalent bacterial pathogen, induces chronic gastritis and is associated with more than 90% of cases of gastric cancer (GC). However, the introduction of nucleotide sequencing techniques and the development of biocomputional tools have surpassed traditional culturing techniques and opened a wide field for studying the mucosal and luminal composition of the bacterial gastric microbiota beyond H. pylori. In studies applying animal models, a potential role in gastric carcinogenesis for additional bacteria besides H. pylori has been demonstrated. At different steps of gastric carcinogenesis, changes in bacterial communities occur. Whether these microbial changes are a driver of malignant disease or a consequence of the histologic progression along the precancerous cascade, is not clear at present. It is hypothesized that atrophy, as a consequence of chronic gastric inflammation, alters the gastric niche for commensals that might further urge the development of H. pylori-induced GC. Here, we review the current state of knowledge on gastric bacteria other than H. pylori and on their synergism with H. pylori in gastric carcinogenesis.

scholarly journals Phenotypic and Genotypic Analysis of Resistant Helicobacter pylori Strains Isolated from Children with Gastrointestinal Diseases

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 759
Author(s):  
Monika Maria Biernat ◽  
Aldona Bińkowska ◽  
Łukasz Łaczmański ◽  
Paweł Biernat ◽  
Paweł Krzyżek ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Point Mutations ◽  
Gastrointestinal Diseases ◽  
Drug Susceptibility Testing ◽  
Test Method ◽  
Ulcer Disease ◽  
Genotypic Analysis ◽  
Clinical Diagnoses ◽  
H Pylori

Antibiotic resistance of Helicobacter pylori is currently a global issue. The aim of this study was to analyze actual antibiotic resistance rates of H. pylori strains isolated from children with primary infections and to compare the incidence of mutations that determine resistance to clarithromycin (CH) and metronidazole (MET) in children with different clinical diagnoses. A total of 91 H. pylori strains were isolated from 108 children with primary infections. Drug susceptibility testing of the strains was performed using E-test method. Classical sequencing of DNA fragments was used to detect point mutations for CH and MET resistance. Resistance to CH was detected in 31% of isolated strains (28/91), while resistance to MET and CH was detected in 35% (32/91) of strains. A2143G was the most frequently detected mutation and was dominant among strains isolated from children with peptic ulcer disease (80%). Mutations in the rdxA gene were found significantly more frequently among MET-resistant strains than MET-sensitive strains (p = 0.03, Chi2 = 4.3909). In children, a higher frequency of H. pylori multiresistant strains was observed compared with the previous study in the same area. Differences were found in the occurrence of point mutations among H. pylori strains resistant to CH isolated from children with different clinical diagnoses.

Eradication of Helicobacter pylori: the power of nanosized formulations

Nanomedicine ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. 527-542
Author(s):  
Qianyu Zhang ◽  
Wen Wu ◽  
Jinqiang Zhang ◽  
Xuefeng Xia
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Peptic Ulcer ◽  
Gastric Carcinoma ◽  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Mucosal Barrier ◽  
Harsh Environment ◽  
H Pylori ◽  
Cure Rates

Helicobacter pylori is a pathogen that is considered to cause several gastric disorders such as chronic gastritis, peptic ulcer and even gastric carcinoma. The current therapeutic regimens mainly constitute of a combination of several antimicrobial agents and proton pump inhibitors. However, the prevalence of antibiotic resistance has been significantly lowering the cure rates over the years. Nanocarriers possess unique strengths in this regard owing to the fact that they can protect the drugs (such as antibiotics) from the harsh environment in the stomach, penetrate the mucosal barrier and deliver drugs to the desired site. In this review we summarized recent studies of different antibacterial agents orally delivered by nanosized carriers for the eradication of H. pylori.

scholarly journals A Next-Generation Sequencing-Based Approach to Identify Genetic Determinants of Antibiotic Resistance in Cambodian Helicobacter pylori Clinical Isolates

2019 ◽  
Vol 8 (6) ◽  
pp. 858 ◽  
Author(s):  
Vo Phuoc Tuan ◽  
Dou Narith ◽  
Evariste Tshibangu-Kabamba ◽  
Ho Dang Quy Dung ◽  
Pham Thanh Viet ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Genetic Resistance ◽  
23S Rrna ◽  
Next Generation ◽  
Genetic Determinants ◽  
Resistance Determinants ◽  
Genotypic Analysis ◽  
H Pylori ◽  
Resistant Genotypes

We evaluated the primary resistance of Helicobacter pylori (H. pylori) to routinely used antibiotics in Cambodia, an unexplored topic in the country, and assessed next-generation sequencing’s (NGS) potential to discover genetic resistance determinants. Fifty-five H. pylori strains were successfully cultured and screened for antibiotic susceptibility using agar dilution. Genotypic analysis was performed using NGS data with a CLC genomic workbench. PlasmidSeeker was used to detect plasmids. The correlation between resistant genotypes and phenotypes was evaluated statistically. Resistances to metronidazole (MTZ), levofloxacin (LVX), clarithromycin (CLR), and amoxicillin (AMX) were 96.4%, 67.3%, 25.5%, and 9.1%, respectively. No resistance to tetracycline (TET) was observed. Multi-drug resistance affected 76.4% of strains. No plasmids were found, but genetic determinants of resistance to CLR, LVX, and AMX were 23S rRNA (A2146G and A2147G), GyrA (N87K and D91Y/N/G), and pbp1 (P473L), respectively. No determinants were genetically linked to MTZ or TET resistance. There was high concordance between resistant genotypes and phenotypes for AMX, LVX, and CLR. We observed high antibiotic resistance rates of CLR, MTZ, and LVX, emphasizing the need for periodic evaluation and alternative therapies in Cambodia. NGS showed high capability for detecting genetic resistance determinants and potential for implementation in local treatment policies.

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