Helicobacter Pylori Resistance Research Articles

Epidemiological study of antibiotic-resistant Helicobacter pylori in Brazil a meta-analysis

Objectives: To evaluate the proportion of Helicobacter pylori resistant to tetracyclines, amoxicilline, furazolidone, clarithromycin, fluoroquinolones and amoxicillin in Brazil and to present genotypic characteristics of strains. Methodology: Search in PubMed, SciELO, VHL and Medline. Twelve Brazilian studies on resistant Helicobacter pylori were selected, with a total of 2,038 patients. The options were performed with a confidence interval of 95% and an alpha of 0.05 using the software RStudio5.0. Results: low resistance rate for 04 antibiotics, being lower than the 15% threshold considered for empirical treatment. However, for metronidazole the rate of 43% and clarithromycin 16% macrolide and amoxicillin increased resistance when compared to previous years. The Southeast region had the highest rates. A clarithromycin ae A2147 in the 23s 23s RNA gene was the most prevalent conferring clear resistance. Conclusion: The increase in resistance to clarithromycin and amoxicillin resistance demonstrates that the factors that still increase for the acquisition of resistance still exist. Therefore, constant epidemiological surveillance is necessary so that we are aware of the resistance profile, performing assertive therapy.

Experience of using different schemes of eradication therapy for Helicobacter pylori infection and their effectiveness in Ukraine

Background. The resistance of Helicobacter pylori (H.pylori) to antibacterial drugs has increased in recent years. This is primarily due to the unwarranted use of antibiotics, as demonstra­ted by the recent COVID-19 pandemic. The choice of the optimal regimen and duration of treatment are current issues today. The aim: retrospective study on the effectiveness of 14-day H.pylori eradication regimens used in 2022–2023 and comparison of their effectiveness and safety with those of 10-day regimens used in 2020–2021 in Ukraine. Materials and methods. The data of 242 patients (123 men and 119 women) aged 18 to 65 years with chronic gastritis, peptic ulcer of the duodenum and stomach associated with H.pylori were analyzed retrospectively. All patients were treated with standard regimens according to the Maastricht V and VI Consensus. H.pylori infection was confirmed by a rapid urease test, determination of fecal antigen and histologically. Results. As a result of the study, it was found that 10-day regimens with triple therapy had an efficiency of 80–81 %. The effectiveness of a 14-day triple therapy with esomeprazole and lansoprazole was significantly higher compared to a 10-day regimen, 85 and 86 %, respectively (p < 0.05). Howe­ver, the frequency of side effects was higher with a 14-day therapy. A 10-day triple regimen with levofloxacin compared to a standard 10-day triple therapy had the lowest efficacy of 78 %. But when levofloxacin therapy was increased to 14 days, its effectiveness became comparable to that of a 14-day triple therapy, 85 %. The highest efficiency was demonstrated by a 10-day and 14-day therapy with furazolidone, which was added to amoxicillin and levofloxacin: 95 and 97.8%, respectively. Conclusions. The effectiveness of schemes with clarithromycin in Ukraine remains high. Taking drugs for 14 days increases the percentage of H.pylori eradication and the frequency of unwanted effects. Addition of furazolidone to levofloxacin and amo­xicillin increases the rate of successful H.pylori eradication.

Research on Key Technologies of Microarray Chips for Detecting Drug-Resistant Genes in Helicobacter pylori.

In addressing the detection of drug resistance in Helicobacter pylori, we have successfully developed an efficient and highly accurate detection methodology. Initially, we designed and fabricated a microarray chip, which underwent finite element analysis for its optical and thermal characteristics. Ultimately, COC material was chosen as the processing material for the chip, ensuring superior performance. Subsequently, we established a comprehensive detection system and validated its performance. Following that, comparative experiments were conducted for detecting drug resistance in H. pylori. The experimental results indicate that our established methodology aligns with the results obtained using the E-test detection kit, achieving a concordance rate of 100%. In comparison to the E-test detection kit, our methodology reduces the detection time to 1.5 h and provides a more extensive coverage of detection sites.

Sodium sulfite-driven Helicobacter pylori eradication: Unraveling oxygen dynamics through multi-omics investigation

Due to the emergence and spread of multidrug resistance in Helicobacter pylori (H. pylori), its eradication has become difficult. Sodium sulfite (SS), a widely used food additive for ensuring food safety and storage, has been recognized as an effective nonbactericidal agent for H. pylori eradication. However, the mechanism by which H. pylori adapts and eventually succumbs under low- or no-oxygen conditions remains unknown. In this study, we aimed to evaluate the anti-H. pylori effect of SS and investigated the multiomics mechanism by which SS kills H. pylori. The results demonstrated that SS effectively eradicated H. pylori both in vitro and in vivo. H. pylori responds to the oxygen changes regulated by SS, downregulates the HcpE gene, which is responsible for redox homeostasis in bacteria, decreases the activities of enzymes related to oxidative stress, and disrupts the outer membrane structure, increasing susceptibility to oxidative stress. Furthermore, SS downregulates the content of cytochrome C in the microaerobic respiratory chain, leading to a sharp decrease in ATP synthesis. Consequently, the accumulation of triglycerides (TGs) in bacteria due to oxidative stress supports anaerobic respiration, meeting their energy requirements. The multifaceted death of H. pylori caused by SS does not result in drug resistance. Thus, screening of the redox homeostasis of HcpE as a new target for H. pylori infection treatment could lead to the development of a novel approach for H. pylori eradication therapy.

Antibiotic resistance in Helicobacter pylori among children and adolescents in East Asia: A systematic review and meta-analysis.

In East Asia, Helicobacter pylori (H. pylori) infection and related diseases are common, primarily during childhood and adolescence. The rates of primary antibiotic resistance in H. pylori among East Asian children and adolescents have not been extensively explored; few relevant systematic reviews or meta-analyses have been conducted. We evaluated the rates of antibiotic resistance in H. pylori among East Asian children and adolescents, with the goal of facilitating individualized treatment recommendations. We searched PubMed, Embase, and the Cochrane Library for studies in any language published up to February 2023 that explored antibiotic resistance in H. pylori among East Asian children and adolescents. We used MeSH and non-MeSH terms related to the topic, including terms related to children, adolescents, antibiotic resistance, H. pylori, and nations or regions. Additionally, we reviewed the reference lists of relevant articles. Studies that matched our strict predefined eligibility criteria were included in the screening process. Using established assessment methods, we evaluated the quality of the included studies. We identified 15 observational studies involving 4831 H. pylori isolates, all published between 2001 and 2022. There was substantial primary antibiotic resistance in H. pylori isolates from East Asian children and adolescents. The rates of primary resistance were 51% (95% confidence interval [CI]: 40-62%) for metronidazole; 37% (95% CI: 20-53%) for clarithromycin; 19% (95% CI: 11-28%) for levofloxacin; and less than 3% each for amoxicillin, tetracycline, and furazolidone. Subgroup analysis revealed a prominent increase in metronidazole resistance over time. Clarithromycin and levofloxacin resistance rates fluctuated between 2005 and 2015, then remained stable; other antibiotic resistance rates were generally stable. Metronidazole, clarithromycin, and levofloxacin resistance rates were significantly higher in the Chinese mainland than in other East Asian regions. The rates of dual and multiple antibiotic resistance were 28% (95% CI: 21-36%) and 10% (95% CI: 7-14%), highlighting the potential for diverse resistance patterns. H. pylori isolates from East Asian children and adolescents exhibit high levels of metronidazole and clarithromycin resistance, particularly in the Chinese mainland. The non-negligible rates of dual and multiple resistance highlight the complexity of this problem. PROSPERO, No. IDCRD42023402510.

Testing for Helicobacter pylori in an era of antimicrobial resistance.

Antimicrobial resistance in Helicobacter pylori has reached alarming levels and is compromising traditional empiric treatment of H. pylori. Antimicrobial susceptibility testing is routinely performed for infectious diseases when there is a risk of resistance and is now recommended to guide therapy for H. pylori. This mini-review overviews the current diagnostics for H. pylori with a focus on tests that enable susceptibility-guided treatment, including molecular tests performed directly on stool and endoscopically collected specimens.

Antibiotic Resistance in Helicobacter pylori Isolates from Northwestern and Central Romania Detected by Culture-Based and PCR-Based Methods.

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.

Drug-Resistant Helicobacter pylori: Diagnosis and Evidence-Based Approach.

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.

Epiberberine inhibits Helicobacter pylori and reduces host apoptosis and inflammatory damage by down-regulating urease expression

Ethnopharmacological relevanceWith dramatically increasing antibiotic resistance in Helicobacter pylori (H. pylori), it is urgent to find alternative therapeutic agents. Rhizoma Coptidis is a traditional Chinese medicine for gastrointestinal diseases and shows excellent anti-H. pylori effect. Epiberberine (EPI), as one of the major alkaloids of Rhizoma Coptidis, has been reported to have urease-inhibiting activity, but its scavenging effect on H. pylori and the potential mechanism remain unclear. Aim of the studyTo investigate the inhibitory effect of EPI on H. pylori and explore its multi-action on Helicobacter pylori urease (HPU). Materials and methodsUsing minimum inhibitory concentration (MIC) assay, minimum bactericidal concentration (MBC) assay, growth inhibition kinetics assay, bacterial resistance development, transmission electron microscope (TEM) assay, and animal experiments to investigate the inhibitory effect of EPI on H. pylori in vitro and in vivo. Using the Berthelot method, molecular docking and thermal displacement experiments to verify that EPI inhibits urease activity by interacting with HPU. Using transcriptome data, Real-Time PCR (RT-PCR) experiments to investigate the alterations in the expression of urease subunit ureB gene after EPI treatment. Using MTT cell viability assay, Hoechst 33342 staining method, JC-1 reagent detection method, western blot experiments, and Griess method to investigate the anti-apoptosis and anti-inflammation actions of EPI on gastric epithelial cells (GES-1) induced by HPU. ResultsIn vitro experiments proved that EPI has significant anti-H. pylori activity without drug resistance, induces H. pylori fragmentation and apoptosis. In vivo experiments showed that EPI has a certain clearance effect of H. pylori, and can reduce gastric inflammation caused by H. pylori infection. Transcriptome data, RT-PCR experiments, and other experiments demonstrate that EPI has a triple effect: (1) inhibiting the expression of HPU subunits ureB, (2) directly inhibiting urease activity by interacting with HPU, and (3) inhibiting HPU-induced apoptosis and inflammation in GES-1. ConclusionsEPI is an excellent anti-H. pylori agent and reduces host apoptosis and inflammation by inhibiting the activity of urease and down-regulating the expression of ureB.

Overcoming Antibiotic Resistance in Helicobacter Pylori: The Promise of Non-Antibiotic Therapies

Overcoming Antibiotic Resistance in Helicobacter Pylori: The Promise of Non-Antibiotic Therapies

Research on antibiotic resistance in Helicobacter pylori: a bibliometric analysis of the past decade.

Resistance of Helicobacter pylori (H. pylori) to antibiotics has reached alarming levels worldwide, and the efficacy of the H. pylori eradication treatment has decreased dramatically because of antibiotic resistance. To gain a more comprehensive understanding of the development status, research hotspots, and future trends related to H. pylori antibiotic resistance, we conducted a thorough retrospective analysis via the bibliometrics method. We searched the Science Citation Index Expanded of the Web of Science Core Collection for all pertinent articles on H. pylori antibiotic resistance from 2013 to 2022. R-bibliometrix, CiteSpace, and VOSviewer tools were utilized to depict statistical evaluations in order to provide an unbiased presentation and forecasts in the field. We incorporated a total of 3,509 articles related to H. pylori antibiotic resistance. Publications were inconsistent prior to 2017, but steadily increased after 2017. China generated the most papers and the United States of America received the most citations and the highest H-index. Baylor College of Medicine was the most influential institution in this field, with the highest number of publications and citations, as well as the highest H-index. Helicobacter was the most productive journal, followed by the World Journal of Gastroenterology and Frontiers in Microbiology. The World Journal of Gastroenterology had the highest citation. Graham, David Y was the most productive and cited author. Clarithromycin resistance, prevalence, gastric cancer, quadruple therapy, sequential therapy, 23S rRNA, whole genome sequencing, bismuth, and probiotics appeared with a high frequency in the keywords. The top keywords with the highest citation bursts were vonoprazan, RdxA, biofilm formation, and fatty acid chain. Our research illustrated a multi-dimensional facet and a holistic knowledge structure for H. pylori antibiotic resistance research over the past decade, which can serve as a guide for the H. pylori research community to conduct in-depth investigations in the future.

Primary antibiotic resistance in Helicobacter pylori in China: a systematic review and meta-analysis

The incidence of Helicobacter pylori (HP) is 25-50% in developed countries and 80% in developing countries, including 56.2% in China. However, antibiotic resistance of HP is a threat to HP control. The purpose of this study was to comprehensively evaluate primary drug resistance of HP in China. The full text of reports of the primary antibiotic resistance prevalence of HP was obtained from multiple databases (PubMed, Web of Science, Evimed, Cochrane Library, and China National Knowledge Internet). Review Manager 5.2 was adopted for meta-analysis, sensitivity analysis, and bias analysis. The Newcastle-Ottawa Scale was used to assess the article quality. In total, 38804 HP samples from 22 trials were extracted. The results suggested that the overall prevalence of amoxicillin, clarithromycin, metronidazole, and levofloxacin resistance among HP in adults was as follows: mean difference (MD)=1.35%, 95% confidence interval (CI) [1.03%, 1.68%]; MD=23.76%, 95% CI [20.23%, 27.3%]; MD=69.32%, 95% CI [64.85%, 73.8%]; and MD=29.45%, 95% CI [4.90, 176.96], respectively. From the results of sensitivity and publication bias, we find that these results are robust and had little publication bias. Our research showed that in China, the prevalence of HP resistance to primary antibiotics warrants attention, especially with regard to metronidazole, levofloxacin, and clarithromycin.

Gastric microbiome changes in relation with Helicobacter pylori resistance.

Inadequate antimicrobial treatment has led to multidrug-resistant (MDR) bacteria, including Helicobacter pylori (H. pylori), which one of the notable pathogens in the stomach. Antibiotic-induced changes in the microbiota can negatively affect the host. This study aimed to determine the influence of H. pylori resistance on the diversity and abundance of the stomach microbiome. Bacterial DNA was extracted from biopsy samples of patients presenting dyspepsia symptoms with H. pylori positive from cultures and histology. DNA was amplified from the V3-V4 regions of the 16S rRNA gene. In-vitro E-test was used to detect antibiotic resistance. Microbiome community analysis was conducted through α-diversity, β-diversity, and relative abundance. Sixty-nine H. pylori positive samples were eligible after quality filtering. Following resistance status to five antibiotics, samples were classified into 24 sensitive, 24 single resistance, 16 double resistance, 5 triple resistance. Samples were mostly resistant to metronidazole (73.33%; 33/45). Comparation of four groups displayed significantly elevated α-diversity parameters under the multidrug resistance condition (all P <0.05). A notable change was observed in triple-resistant compared to sensitive (P <0.05) and double-resistant (P <0.05) groups. Differences in β-diversity by UniFrac and Jaccard were not significant in terms of the resistance (P = 0.113 and P = 0.275, respectively). In the triple-resistant group, the relative abundance of Helicobacter genera was lower, whereas that of Streptococcus increased. Moreover, the linear discriminant analysis effect size (LEfSe) was associated with the presence of Corynebacterium and Saccharimonadales in the single-resistant group and Pseudomonas and Cloacibacterium in the triple-resistant group. Our results suggest that the resistant samples showed a higher trend of diversity and evenness than the sensitive samples. The abundance of H. pylori in the triple-resistant samples decreased with increasing cohabitation of pathogenic bacteria, which may support antimicrobial resistance. However, antibiotic susceptibility determined by the E-test may not completely represent the resistance status.

High-throughput screening and molecular dynamics simulations of natural products targeting LuxS/AI-2 system as a novel antibacterial strategy for antibiotic resistance in Helicobacter pylori

The main goal of treating any Helicobacter pylori (H. pylori)-related gastrointestinal disease is completely eradicating infection. Falling eradication efficiency, off-target effects, and patient noncompliance with prolonged and broad spectrums have sparked clinical interest in exploring other effective, safer therapeutic choices. As natural substances are risk-free and privileged with high levels of antibacterial activity, most of these natural chemical’s specific modes of action are unknown. With the aid of in silico molecular docking-based virtual screening studies and molecular dynamic simulations, the current study is intended to gather data on numerous such natural chemicals and assess their affinity for the S-ribosyl homocysteine lyase (LuxS) protein of H. pylori. The ligand with the highest binding energy with LuxS, glucoraphanin, catechin gallate and epigallocatechin gallate were rationally selected for further computational analysis. The solution stability of the three compounds’ optimal docking postures with LuxS was initially assessed using long-run molecular dynamics simulations. Using molecular dynamics simulation, the epigallocatechin gallate was found to be the most stable molecule with the highest binding free energy, indicating that it might compete with the natural ligand of the inhibitors. According to ADMET analysis, his phytochemical was a promising therapeutic candidate for an antibacterial action since it had a range of physicochemical, pharmacokinetic, and drug-like qualities and had no discernible adverse effects. Additional in vitro, in vivo, and clinical trials are needed to confirm the drug’s precise efficacy during H. pylori infection. Communicated by Ramaswamy H. Sarma

Bibliometric analysis of Helicobacter pylori resistance-from 2002 to 2022.

Drug resistance in Helicobacter pylori severely affects the efficacy of eradication therapy, and a number of studies have been conducted on this issue. The aim of this study was to assess the progress in this field using a bibliometric approach. Publications related to H. pylori resistance from 2002 to 2022 were retrieved from the Web of Science database. Relevant information including titles, authors, countries, and keywords was extracted, and the data were processed using Excel, VOSviewer, and CiteSpace software for co-authorship, co-citation, and co-occurrence analysis. From 2002 to 2022 (as of 09/24/2022), the field of H. pylori-resistance research produced a total of 2677 publications with a total of 75217 citations, with an overall upward trend in the annual number of articles published, reaching a peak of 204 in 2019. Articles were mainly published in Q1 or Q2 journals, with Helicobacter (TP = 261) publishing the most literature, Baylor College of Medicine (TP = 68) and Deng-chyang wu (TP = 38) being the most prolific institutions and authors, respectively. China and the United States were the locations of most of the articles, accounting for 35.08% of the global publication volume. Keyword co-occurrence analysis divided H. pylori-resistance research into four clusters: "Therapeutic Strategies," "Diseases," "Mechanism Research and Epidemiology," and "Drug Research." "Drug research" and burst detection indicate that the current research hotspot involves the selection and analysis of treatment strategies. H. pylori-resistance research has become a popular research field, and although there are significant contributions from Europe, the United States, and East Asia, there are significant imbalances between regions that cannot be ignored. In addition, the exploration of treatment strategies remains a key issue for research at the current stage.

Novel Mutations Conferring Amoxicillin Resistance in Helicobacter pylori in South Korea.

Helicobacter pylori is the primary causative agent of gastritis, gastric ulcers, duodenal ulcers, gastric cancer, and peripheral B-cell lymphoma. H. pylori eradication often fails due to elevated antibiotic resistance. However, no previous studies have thoroughly examined amoxicillin resistance. Here, the objective was to identify clinical strains of H. pylori with amoxicillin resistance and to analyze single-nucleotide polymorphisms (SNPs) associated with amoxicillin resistance. From March 2015 to June 2019, genotypic and phenotypic amoxicillin resistance was analyzed using an E-test and whole-genome sequencing (WGS). Analysis of 368 clinical strains confirmed amoxicillin resistance in 31 strains (resistance rate of 8.7%). The genomes were extracted from nine resistant (<0.125 mg/L) strains, and WGS was performed for genetic analysis. WGS analysis identified SNPs present in pbp1a, pbp2, nhaC, hofH, hofC, and hefC in all nine isolates. Some of these genes may be related to amoxicillin resistance. A total of six SNPs (A69V, V374L, S414R, T503I, A592D, and R435Q) were identified in PBP2 of H-8, the most resistant strain. We predict that these six SNPs are associated with high amoxicillin resistance. Amoxicillin resistance should be considered in the clinical setting for the treatment failure of H. pylori eradication.

Antibacterial, Antibiofilm and Anti-Inflammatory Activities of Eugenol Clove Essential Oil against Resistant Helicobacter pylori.

Eugenol essential oil (EEO) is the major component in aromatic extracts of Syzygium aromaticum (clove) and has several biological properties, such as antibacterial, antioxidant, and anti-inflammatory activities, as well as controlling vomiting, coughing, nausea, flatulence, diarrhea, dyspepsia, stomach distension, and gastrointestinal spasm pain. It also stimulates the nerves. Therefore, the aim of this study was to extract and purify EEO from clove buds and assess its ability to combat resistant Helicobacter pylori. Additionally, EEO's anti-inflammatory activity and its ability to suppress H. pylori biofilm formation, which is responsible for antibiotic resistance, was also investigated. Syzygium aromaticum buds were purchased from a local market, ground, and the EEO was extracted by using hydro-distillation and then purified and chemically characterized using gas chromatography-mass spectrometry (GC-MS). A disk-diffusion assay showed that Helicobacter pylori is sensitive to EEO, with an inhibition zone ranging from 10 ± 06 to 22 ± 04 mm. The minimum inhibition concentration (MIC) of EEO ranged from 23.0 to 51.0 μg/mL against both Helicobacter pylori clinical isolates and standard strains. In addition, EEO showed antibiofilm activity at 25 µg/mL and 50 µg/mL against various Helicobacter pylori strains, with suppression percentages of 49.32% and 73.21%, respectively. The results obtained from the anti-inflammatory assay revealed that EEO possesses strong anti-inflammatory activity, with human erythrocyte hemolysis inhibition percentages of 53.04, 58.74, 61.07, and 63.64% at concentrations of 4, 8, 16, and 32 μg/L, respectively. GC-MS analysis revealed that EEO is a major component of Syzygium aromaticum when extracted with a hydro-distillation technique, which was confirmed by its purification using a chemical separation process. EEO exhibited antibacterial action against resistant Helicobacter pylori strains, as well as antibiofilm and anti-inflammatory activities, and is a promising natural alternative in clinical therapy.

Multiple amino acid substitutions in penicillin-binding protein-1A confer amoxicillin resistance in refractory Helicobacter pylori infection.

Amoxicillin resistance in Helicobacter pylori is mainly associated with mutations in penicillin-binding protein-1A (PBP-1A). However, the specific amino acid substitutions in PBP-1A that confer amoxicillin resistance in H. pylori remain to be investigated. This study aimed to investigate the molecular mechanism underlying amoxicillin resistance in patients with refractory H. pylori infection. Esophagogastroduodenoscopy (EGD) was performed in patients with persistent H. pylori infection after at least two courses of H. pylori eradication therapy between January-2018 to March-2021. Refractory H. pylori was cultured from the gastric biopsy specimens. Antibiotic susceptibility testing was conducted to determine the minimum inhibitory concentrations (MICs). Sequence analysis of pbp-1A was performed for amoxicillin-resistant strains. Thirty-nine successfully cultured isolates were classified as refractory H. pylori isolates, and seventeen isolates were resistant to amoxicillin (MIC > 0.125mg/L). Sequence analysis of resistant strains showed multiple mutations in the C-terminal region of PBP-1A that conferred amoxicillin resistance in H. pylori. However, the number of PBP-1A mutations did not correlate with the high MICs of amoxicillin-resistant isolates. Notably, some amino acid substitutions were identified in all Taiwanese isolates with history of eradication failure but not in published amoxicillin-susceptible strains, suggesting that the mutations may play a role in conferring antibiotic resistance to these strains. Our results show that amoxicillin resistance in refractory H. pylori is highly correlated with numerous PBP-1A mutations that are strain specific. Continuous improvements in diagnostic tools, particularly molecular analysis approaches, can help to optimize current antimicrobial regimens.

Initial data on Helicobacter pylori resistance in Lebanon

Initial data on Helicobacter pylori resistance in Lebanon

Uncovering Genetic Determinants of Antibiotic Resistance in Helicobacter pylori through Next-Generation Sequencing and Genome-Wide Association Study

Uncovering Genetic Determinants of Antibiotic Resistance in Helicobacter pylori through Next-Generation Sequencing and Genome-Wide Association Study