scholarly journals Antimicrobial Resistance and Genetic Characteristics that Might be Related to Antibiotic Resistance of 112 Helicobacter Pylori Shanghai Isolates

2021 ◽  
Author(s):  
Yixin Liu ◽  
Su Wang ◽  
Feng Yang ◽  
Wenjing Chi ◽  
Li Ding ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
23S Rrna ◽  
Intrinsic Resistance ◽  
Phenotypic Analysis ◽  
Gastric Diseases ◽  
Genetic Characteristics ◽  
Treatment Regimens ◽  
H Pylori ◽  
Susceptible Populations

Abstract Background Shanghai, east China has one of the world’s highest burdens of Helicobacter pylori infection. While multidrug regimens can effectively eradicate H. pylori, antibiotic-resistant (AR) H. pylori has been recognized by the WHO as ‘high priority’ for urgent need of new therapies. Moreover, the genetic characteristics of H. pylori AR in Shanghai is under-reported. The purpose of this study was to determine the resistance prevalence, re-substantiate resistance-conferring mutations, and investigate novel genetic elements might be related to H. pylori AR. Results We performed a whole-genomic and phenotypic analysis of 112 H. pylori isolated from gastric biopsy specimens from a population with different gastric diseases and residing in Shanghai. No strains were resistant to amoxicillin. Levofloxacin, metronidazole and clarithromycin resistance was observed in 39, 73 and 18 isolates, respectively. There was no association between gastroscopy diagnosis and resistance phenotypes. We reported the presence or absence of several subsystem proteins including hopE, hofF, spaB, cagY and pflA, and a combination of CRISPRs, which were potentially correlated with resistance phenotypes. The H. pylori isolates were also annotated for AR genes to define a resistome containing 80 genes. A resistome-wide association study (RWAS) was performed for the three antibiotics by correlating the phenotypes with the variation data. The RWAS correctly identified the well-known intrinsic resistance associated mutations for levofloxacin (N87T/I and/or D91G/Y mutations in gyrA), metronidazole (I38V mutation in fdxB), and clarithromycin (A2143G and/or A2142G mutations in 23S rRNA), and added 174 novel variations, with 23 nsSNPs and 48 fsIndels significantly enriched in resistant or susceptible populations. The variant-level linkage disequilibrium analysis demonstrated a series of variations with strong co-occurring correlation with known mutations, and highlighted the underlying role of a protease Lon. Conclusion Our study indicated H. pylori isolates from Shanghai exhibit multidrug antibiotic resistance, and identified specific genomic characteristics in relation to H. pylori AR in Shanghai. Continued surveillance of H. pylori AR in Shanghai is warranted in order to establish appropriate eradication treatment regimens for this population.

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.

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 Microarray-Based Detection and Clinical Evaluation for Helicobacter pylori Resistance to Clarithromycin or Levofloxacin and the Genotype of CYP2C19 in 1083 Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yi Song ◽  
Fengna Dou ◽  
Zhe Zhou ◽  
Ningmin Yang ◽  
Jing Zhong ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Limit Of Detection ◽  
Eradication Therapy ◽  
Gastric Biopsy ◽  
Individual Therapy ◽  
23S Rrna ◽  
Antibiotic Administration ◽  
Cyp2c19 Polymorphism ◽  
H Pylori

Background. Helicobacter pylori (H. pylori) is one of the most frequent and persistent bacterial infections that affect nearly half of the world’s population. Antibiotic resistance is a constantly evolving process and local surveillance of antibiotic resistance is warranted to guide clinicians in their choice of therapy. The aim of this study was to establish a microarray-based detection to identify H. pylori infection, clarithromycin and levofloxacin susceptibility, and CYP2C19 genetic polymorphism and guide to potential choice of proton pump inhibitor (PPI), antibiotic administration for tailored H. pylori eradication therapy. Methods. By analyzing the sequence of human genomic CYP2C19⁎2 and CYP2C19⁎3 and mutations within the 23S rRNA and gyrA gene regions conferring clarithromycin and levofloxacin resistance, respectively, we developed a microarray for individual therapy detection of H. pylori infection. Plasmids were established as positive or limit of detection (LOD) reference materials. The specificity and sensitivity of the microarray had been performed. And a total of 1083 gastric biopsy samples were tested and the Kappa value had been calculated between the array and Sanger sequencing. We also analyzed the resistance to clarithromycin and levofloxacin in China, as well as the CYP2C19 polymorphisms. Results. The LOD of detecting H. pylori was 103 CFU/mL and human genome DNA was 2 ng/μL. The detection results of 1083 gastric biopsy samples showed that 691 (63.80%) were H. pylori positive, of which 266 (38.49%) were resistant to clarithromycin, 192 (27.79%) were resistant to levofloxacin, and 61 (8.83%) were resistant to both of them. For the type of CYP2C19 polymorphism, 412 (38.04%) were homozygous fast type (HomEM), 574 (53%) were heterozygous EM (HetEM), and 97 (8.96%) were poor metabolizer (PM). Conclusions. The proposed microarray-based detection has high specificity, sensitivity, and reproducibility for detecting the resistance of clarithromycin or levofloxacin as well as CYP2C19 polymorphism, which may help to improve the clinical eradication rate of H. pylori.

scholarly journals High Prevalence of Antibiotic Resistance in Iranian Helicobacter pylori Isolates: Importance of Functional and Mutational Analysis of Resistance Genes and Virulence Genotyping

2019 ◽  
Vol 8 (11) ◽  
pp. 2004 ◽  
Author(s):  
Nastaran Farzi ◽  
Abbas Yadegar ◽  
Amir Sadeghi ◽  
Hamid Asadzadeh Aghdaei ◽  
Sinéad Marian Smith ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Rrna Genes ◽  
23S Rrna ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Gyra Gene ◽  
Therapeutic Regime ◽  
High Prevalence ◽  
H Pylori

The high prevalence of antibiotic resistance in Helicobacter pylori has become a great challenge in Iran. The genetic mutations that contribute to the resistance have yet to be precisely identified. This study aimed to investigate the prevalence of antibiotic resistance and virulence markers in Iranian H. pylori isolates and to analyze if there is any association between resistance and genotype. Antibiotic susceptibility patterns of 68 H. pylori isolates were investigated against metronidazole, clarithromycin, amoxicillin, rifampicin, ciprofloxacin, levofloxacin, and tetracycline by the agar dilution method. The frxA, rdxA, gyrA, gyrB, and 23S rRNA genes of the isolates were sequenced. The virulence genotypes were also determined using PCR. Metronidazole resistance was present in 82.4% of the isolates, followed by clarithromycin (33.8%), ciprofloxacin (33.8%), rifampicin (32.4%), amoxicillin (30.9%), levofloxacin (27.9%), and tetracycline (4.4%). Overall, 75% of the isolates were resistant to at least two antibiotics tested and considered as a multidrug resistance (MDR) phenotype. Most of the metronidazole-resistant isolates carried frameshift mutations in both frxA and rdxA genes, and premature termination occurred in positions Q5Stop and Q50Stop, respectively. Amino acid substitutions M191I, G208E, and V199A were predominantly found in gyrA gene of fluoroquinolone-resistant isolates. A2143G and C2195T mutations of 23S rRNA were found in four clarithromycin-resistant isolates. Interestingly, significant associations were found between resistance to metronidazole (MNZ) and cagA-, sabA-, and dupA-positive genotypes, with p = 0.0002, p = 0.0001, and p = 0.0001, respectively. Furthermore, a significant association was found between oipA “on” status and resistance to amoxicillin (AMX) (p = 0.02). The prevalence of H. pylori antibiotic resistance is high in our region, particularly that of metronidazole, clarithromycin, ciprofloxacin, and MDR. Simultaneous screening of virulence and resistance genotypes can help clinicians to choose the appropriate therapeutic regime against H. pylori infection.

scholarly journals Antibiotic resistance of Helicobacter pylori in Mongolia

2017 ◽  
Vol 11 (11) ◽  
pp. 887-894 ◽  
Author(s):  
Mandkhai Bolor-Erdene ◽  
Bira Namdag ◽  
Yoshio Yamaoka ◽  
Sarantuya Jav
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Antibiotic Sensitivity ◽  
Upper Gastrointestinal Endoscopy ◽  
Rapid Urease Test ◽  
Treatment Regimens ◽  
Urease Test ◽  
H Pylori ◽  
Strip Testing ◽  
Resistance Rates

Introduction.The resistance of Helicobacter pylori to recently available antibiotic treatment regimens has been recognized as a growing problem. Therefore, the aim of this study was to determine the prevalence of antibiotic resistance among H. pylori strains isolated from Mongolians. Methodology. All gastric biopsy specimens were obtained during upper gastrointestinal endoscopy from patients referred for the exploration of dyspepsia. The urease positive samples by rapid urease test were cultured according to standard microbiological procedures and H. pylori were grown under microaerophilic conditions on selective Pylori agar. H. pylori antibiotic sensitivity was examined using E-test. In addition, the mutations of the corresponding gene were studied by GenoType HelicoDR DNA strip testing. Results. Three hundred twenty patients, 216 female and 104 male in the ages range of 18 to 83 years were included in this study. Rapid urease test yielded positive results for 65.9% (211/320). Among them, we have successfully obtained 72% H. pylori isolates. The antibiotic resistance rates were 35.5% for clarithromycin, 68.4% metronidazole, 23.0% amoxicillin, 25.0% tetracycline, 28.2% erythromycin and 14.5% nitrofuranton. Resistance for 2 drugs was 34.5% and that of 3 drugs was observed in 14.5% of isolates. The most prevalent mutation was A2147G followed by A2146G and D91Y. The prevalence of H. pylori infection increased among Mongolian population and the prevalence of resistance of H. pylori is very high to metronidazole, and moderate to clarithromycin. Conclusion. The data on antimicrobial susceptibilities provided by the present study is may assist the clinicians on the effectiveness of treatment regimens.

scholarly journals Resistotype of Helicobacter pylori isolates: the impact on eradication outcome

2014 ◽  
Vol 63 (5) ◽  
pp. 703-709 ◽  
Author(s):  
Hanafiah Alfizah ◽  
Ahmad Norazah ◽  
Razlan Hamizah ◽  
Mohamed Ramelah
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Eradication Therapy ◽  
Fluoroquinolone Resistance ◽  
23S Rrna ◽  
Nonsense Mutations ◽  
Metronidazole Resistance ◽  
Resistant Strains ◽  
H Pylori ◽  
The Impact

Antibiotic resistance is increasing worldwide, and it has been regarded as the main factor reducing the efficacy of Helicobacter pylori therapy. The aim of this study was to determine the phenotype and genotype of antibiotic-resistant strains of H. pylori in the Malaysian population and to evaluate the impact of antibiotic resistance to eradication outcome. One hundred and sixty-one H. pylori isolates were analysed in this study. Metronidazole, clarithromycin, fluoroquinolone, amoxicillin and tetracycline susceptibilities were determined by Etest. PCR followed by DNA sequencing was carried out to determine mutations. The medical records of the patients infected with resistant strains were reviewed to determine the eradication outcome. Metronidazole resistance was encountered in 36.6 % of H. pylori isolates, whereas clarithromycin and fluoroquinolone resistance was observed in 1.2  and 1.9 % of isolates, respectively. All strains tested were susceptible to amoxicillin and tetracycline. Frameshift and nonsense mutations in rdxA and frxA genes resulting in stop codons contributed to metronidazole resistance, which leads to reduced eradication efficacy. A2142G and A2143G mutations of 23S rRNA were identified as causing failure of the eradication therapy. Mutation at either codon 87 or 91 of the gyrA gene was identified in fluoroquinolone-resistant strains. However, the effect of resistance could not be assessed. This study showed that frameshift and nonsense mutations in rdxA or frxA genes and point mutations in the 23S rRNA affected the efficacy of H. pylori eradication therapy.

scholarly journals High Antibiotic Resistance of Helicobacter pylori and Its Associated Novel Gene Mutations among the Mongolian Population

2020 ◽  
Vol 8 (7) ◽  
pp. 1062
Author(s):  
Dashdorj Azzaya ◽  
Boldbaatar Gantuya ◽  
Khasag Oyuntsetseg ◽  
Duger Davaadorj ◽  
Takashi Matsumoto ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Gene Mutations ◽  
23S Rrna ◽  
Rrna Gene ◽  
Resistance Mutations ◽  
Standard Triple Therapy ◽  
23S Rrna Gene ◽  
H Pylori ◽  
Next Generation Sequencing Ngs

Mongolia has a high prevalence of Helicobacter pylori infection and the second highest incidence of gastric cancer worldwide. Thus, investigating the prevalence of antibiotic resistance and its underlying genetic mechanism is necessary. We isolated 361 H. pylori strains throughout Mongolia. Agar dilution assays were used to determine the minimum inhibitory concentrations of five antibiotics; amoxicillin, clarithromycin, metronidazole, levofloxacin, and minocycline. The genetic determinants of antibiotic resistance were identified with next-generation sequencing (NGS) and the CLC Genomics Workbench. The resistance to metronidazole, levofloxacin, clarithromycin, amoxicillin, and minocycline was 78.7%, 41.3%, 29.9%, 11.9% and 0.28%, respectively. Multidrug resistance was identified in 51.3% of the isolates investigated which were further delineated into 9 antimicrobial resistance profiles. A number of known antibiotic resistance mutations were identified including rdxA, frxA (missense, frameshift), gyrA (N87K, A88P, D91G/N/Y), 23S rRNA (A2143G), pbp1A (N562Y), and 16S rRNA (A928C). Furthermore, we detected previously unreported mutations in pbp1A (L610*) and the 23S rRNA gene (A1410G, C1707T, A2167G, C2248T, and C2922T). The degree of antibiotic resistance was high, indicating the insufficiency of standard triple therapy in Mongolia.

scholarly journals Phenotypic and Genotypic Antibiotic Resistance Patterns in Helicobacter pylori Strains From Ethnically Diverse Population in México

2021 ◽  
Vol 10 ◽  
Author(s):  
Margarita Camorlinga-Ponce ◽  
Alejandro Gómez-Delgado ◽  
Emmanuel Aguilar-Zamora ◽  
Roberto C. Torres ◽  
Silvia Giono-Cerezo ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Indigenous Communities ◽  
Drug Susceptibility ◽  
23S Rrna ◽  
Whole Genome ◽  
Phenotypic Resistance ◽  
H Pylori

Helicobacter pylori strains carry a range of mutations in genes that confer antimicrobial resistance and restrict the available options to treat the infection. Latin America is a region that conserve a large number of indigenous communities relatively isolated that practice a traditional medicine without consumption of drugs. We hypothesized that rates of antibiotic resistance are lower in these communities. Recent progress in whole-genome sequencing has allowed the study of drug susceptibility by searching for the known mutations associated with antibiotic resistance. The aim of this work was to study trends of antibiotic resistance over a 20-year period in Mexican H. pylori strains and to compare susceptibility between strains from Mexican mestizos and from indigenous population; we also aimed to learn the prevalence of mutational patterns in genes gyrA, gyrB, rdxA, frxA, rpsU, omp11, dppA, and 23S rRNA and its association with phenotypic tests. Resistance to clarithromycin, metronidazole, amoxicillin and levofloxacin was determined in167 H. pylori isolates by E-test, and the occurrence of mutational patterns in specific genes was determined by whole genome sequencing (WGS). The trend of resistance over 20 years in mestizo isolates showed significant resistant increase for clarithromycin and levofloxacin to frequencies that banned its clinical use. Resistance in H. pylori isolates of native communities was lower for all antibiotics tested. Phenotypic resistance showed good to moderate correlation with genotypic tests. Genetic methods for characterizing antibiotic resistance require further validation in each population.

scholarly journals Application of Visual Gene Clip-Based Tailored Therapy for the Eradication of Helicobacter pylori

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Lili Yang ◽  
Ao Zou ◽  
Huihua Wu ◽  
Hai Guo ◽  
Fangting Zhang ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Confidence Interval ◽  
Acid Secretion ◽  
Antimicrobial Agents ◽  
Point Mutations ◽  
Eradication Therapy ◽  
23S Rrna ◽  
Tailored Therapy ◽  
H Pylori

Background. Helicobacter pylori eradication with therapies employing a proton pump inhibitor (PPI) and antimicrobial agents is mainly achieved via bacterial susceptibility to antimicrobial agents and the magnitude of acid secretion inhibition. However, annual eradication rates have greatly declined in Mainland China, and therefore, tailored H. pylori eradication regimens that inhibit acid secretion and employ optimal antimicrobial agents determined based on gene clip testing may improve eradication rates. This study was aimed at evaluating the efficacy of tailored H. pylori eradication therapy guided by visual gene clip testing for antibiotic resistance and PPI metabolism genotypes. Methods. This prospective study included 244 patients (141 men and 103 women aged 20–79 years) receiving initial treatment for H. pylori infection. Visual gene clip testing using gastric mucosal specimens was performed to detect antibiotic resistance to clarithromycin conferred by the A2142G and A2143G point mutations of the H. pylori 23S rRNA gene and to levofloxacin conferred by the Asn87 and Asp91 point mutations of the H. pylori gyrA gene. Patients received a 14-day bismuth quadruple therapy regimen guided by testing for antibiotic resistance and CYP2C19 polymorphisms, and primary H. pylori eradication was assessed at least 4 weeks after therapy. Results. H. pylori strains were successfully isolated from the gastric mucosa tissues of 244 patients. Antibiotic resistant isolates were identified in 63 patients, with clarithromycin resistance observed in 50 patients, levofloxacin resistance in 7 patients, and dual resistance in 6 patients. The PPI metabolic genotype of CYP2C19 was detected in 242 of 244 cases, and 97 cases were categorized as extensive metabolizers, 141 as intermediate metabolizers, and 4 as poor metabolizers. Among the 242 patients who received tailored therapy, the H. pylori eradication rate was 90.9% (95% confidence interval 87.3%~94.6%) in the intention-to-treat analysis and 96.9% (95% confidence interval 94.7%~99.2%) in the per protocol analysis. Conclusions. Tailored therapy for H. pylori infection guided by determination of antibiotic resistance and CYP2C19 polymorphism using visual gene chip technology may provide high clinical effectiveness as initial H. pylori eradication therapy.

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