Effect of Temperature on Metronidazole Resistance in Helicobacter pylori

Efficacy of Helicobacter pylori (H. pylori) eradication therapy has declined due to rapid rises in antibiotic resistance. We investigated how increased temperature affected H. pylori (NCTC 11637) growth and its sensitivity to metronidazole in vitro. We performed transcriptomic profiling using RNA-sequencing to identify differentially expressed genes (DEGs) associated with increased temperature. Transcriptional pathways involved in temperature-driven metronidazole resistance changes were analyzed through bioinformatic and literature curation approaches. We showed that H. pylori growth was inhibited at 41°C and inhibition was more apparent with prolonged incubation. Resistance to metronidazole was also reduced—minimum inhibitory concentration for metronidazole decreased from > 256 μg/ml at 37°C to 8 μg/ml at 41°C after culturing for 3 days. RNA-sequencing results, which were highly concordant within treatment conditions, revealed more than one third of genes (583/1,552) to be differentially expressed at increased temperatures with similar proportions up and down-regulated. Quantitative real-time PCR validation for 8 out of 10 DEGs tested gave consistent direction in gene expression changes. We found enrichment for redox and oxygen radical pathways, highlighting a mechanistic pathway driving temperature-related metronidazole resistance. Independent literature review of published genes associated with metronidazole resistance revealed 46 gene candidates, 21 of which showed differential expression and 7 out of 9 DEGs associated with “redox” resistance pathways. Sanger sequencing did not detect any changes in genetic sequences for known resistance genes rdxA, frxA nor fdxB. Our findings suggest that temperature increase can inhibit the growth and reduce H. pylori resistance to metronidazole. Redox pathways are possible potential drivers in metronidazole resistance change induced by temperature. Our study provides insight into potential novel approaches in treating antibiotic resistant H. pylori.

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Current understanding and management of Helicobacter pylori infection: an updated appraisal

F1000Research ◽

10.12688/f1000research.14149.1 ◽

2018 ◽

Vol 7 ◽

pp. 721 ◽

Cited By ~ 6

Author(s):

Shamshul Ansari ◽

Yoshio Yamaoka

Keyword(s):

Helicobacter Pylori ◽

Management Strategy ◽

Asymptomatic Patient ◽

Eradication Therapy ◽

Critical Issue ◽

Effective Management ◽

Timely Diagnosis ◽

Metronidazole Resistance ◽

H Pylori ◽

Resistance Rates

In addition to its role in gastric conditions, Helicobacter pylori has been found to contribute to the development of several non-gastric issues in recent years. Eradication therapy is the only effective management strategy to minimize the H. pylori-related gastric cancer and extra-gastric complications. For an effective “test and treat” strategy, diagnosis and therapy are both important. Because the infection is usually asymptomatic, patient selection is a critical issue for timely diagnosis and many clinical and demographic factors should be considered. Clarithromycin and metronidazole resistance rates also need to be considered while eradication therapy is offered. In this report, we discuss the issues which must be taken into account for the correct and timely diagnosis and for the antibiotic therapy-based management of H. pylori infection.

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Resistotype of Helicobacter pylori isolates: the impact on eradication outcome

Journal of Medical Microbiology ◽

10.1099/jmm.0.069781-0 ◽

2014 ◽

Vol 63 (5) ◽

pp. 703-709 ◽

Cited By ~ 16

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.

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Frequency of rdx A Deletion Mutation Conferring Metronidazole Resistance in Helicobacter pylori

10.51429/ejmm29308 ◽

2020 ◽

Vol 29 (3) ◽

pp. 59-64

Author(s):

Hanaa M. El Maghraby ◽

Samar Mohaseb

Keyword(s):

Helicobacter Pylori ◽

Epigastric Pain ◽

Deletion Mutation ◽

Rapid Urease Test ◽

Rrna Gene ◽

University Hospitals ◽

Metronidazole Resistance ◽

Urease Test ◽

Gastric Biopsies ◽

H Pylori

Background: Metronidazole is one of the antimicrobial drugs that can be used in combination with other drugs for eradication of Helicobacter pylori (H. pylori).Unfortunately, metronidazole resistance in H. plori is an increasing health problem which may be attributed to inactivation of many genes as rdx A gene. Objective: To determine the frequency of rdx A deletion mutation in H. pylori detected in infected patients attending at the Gastroenterology Unit, Zagazig University Hospitals. Methodology: Two gastric biopsies were taken from each enrolled patient by endoscopy. H.pylori detection was done by rapid urease test and polymerase chain reaction (PCR) amplification of 16S rRNA gene. Deletion mutation in rdx A gene was detected by conventional PCR. Results: Out of 134 doubled gastric biopsies obtained from 134 patients, 52.2% were positive for H. pylori. Epigastric pain, vomiting and gastritis were significantly associated with detection of H. pylori infection (p˂ 0.05). Deletion mutation of rdx A gene was detected in 28.6% of H. pylori positive specimens obtained from infected patients. Conclusion: Deletion mutation of rdx A gene is a frequent determinant of rdx A inactivation conferring metronidazole resistance among H. pylori.

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E-Test or Agar Dilution for Metronidazole Susceptibility Testing of Helicobacter Pylori: Importance of the Prevalence of Metronidazole Resistance

10.21203/rs.3.rs-677597/v1 ◽

2021 ◽

Author(s):

Jinnan Chen ◽

Yu Huang ◽

Zhaohui Ding ◽

Xiao Liang ◽

Hong Lu

Keyword(s):

Helicobacter Pylori ◽

Susceptibility Testing ◽

Resistance Rate ◽

Test Method ◽

Major Error ◽

Metronidazole Resistance ◽

Agar Dilution ◽

H Pylori ◽

High Level ◽

Level Resistance

Abstract Background: A number of studies have shown that E-test overestimated the presence of Helicobacter pylori (H. pylori) resistance compared to agar dilution.Objective: The purpose of this study was to explore whether E-test could be an alternative for agar dilution to detect the metronidazole susceptibility of H. pylori.Method: E-test and agar dilution were used to assess susceptibility of H. pylori to metronidazole, clarithromycin and levofloxacin in 281 clinical isolates obtained from China where resistance was high. Cohen kappa analysis, McNemar test, essential and categorical agreement analysis were performed for these two methods. Results: Overall, the result of E-test showed similar prevalence of resistance rate to all antibiotics compared with agar dilution. The essential agreement (EA) of E-test method and agar dilution in the evaluation susceptibility of H. pylori to clarithromycin and levofloxacin were moderate, with 89.0% and 79.7% respectively, but only 45.9% for metronidazole. Results showed categorical agreement (CA) between E-test and agar dilution were 100% for both clarithromycin and levofloxacin. As for metronidazole, the CA was 98.7%, no major error was identified, and rate of very major error was 1.8%.Conclusion: E-test can be an alternative method to detect the metronidazole susceptibility of H. pylori in regions where high-level resistance is common.

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MALT lymphoma: epidemiology, clinical diagnosis and treatment

Journal of Medicine and Life ◽

10.25122/jml-2018-0035 ◽

2018 ◽

Vol 11 (3) ◽

pp. 187-193 ◽

Cited By ~ 13

Author(s):

Petruta Violeta Filip ◽

◽

Denisa Cuciureanu ◽

Laura Sorina Diaconu ◽

Ana Maria Vladareanu ◽

...

Keyword(s):

Helicobacter Pylori ◽

B Cell ◽

Malt Lymphoma ◽

Cell Lymphoma ◽

Gastric Lymphoma ◽

Eradication Therapy ◽

B Cell Lymphoma ◽

Gastric Malt Lymphoma ◽

H Pylori

Primary gastric lymphoma (PGL) represents a rare pathology, which can be easily misdiagnosed because of unspecific symptoms of the digestive tract. Histologically, PGL can vary from indolent marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) to aggressive diffuse large B-cell lymphoma (DLBCL). During the years, clinical trials revealed the important role of Helicobacter pylori (H. pylori) in the pathogenesis of gastric MALT lymphoma. Infection with Helicobacter pylori is an influential promoter of gastric lymphomagenesis initiation. Long-term studies revealed that eradication therapy could regress gastric lymphomas.

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Prevalence of Helicobacter pylori infection among blood donors in Saxony-Anhalt, Germany – a region at intermediate risk for gastric cancer

Zeitschrift für Gastroenterologie ◽

10.1055/s-0043-106311 ◽

2017 ◽

Vol 55 (07) ◽

pp. 653-656 ◽

Cited By ~ 8

Author(s):

Caspar Franck ◽

Armin Hoffmann ◽

Alexander Link ◽

Christian Schulz ◽

Kerstin Wuttig ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Blood Donors ◽

Eradication Therapy ◽

Surrogate Marker ◽

University Hospital ◽

Study Cohort ◽

Emergency Ward ◽

Age Related ◽

H Pylori

Abstract Background In the federal state of Saxony-Anhalt, gastric cancer (GC) incidence ranks among the highest in Germany. Helicobacter pylori prevalence is a surrogate marker for GC risk in a given population. In 2010 we reported an H. pylori seroprevalence of 44.4 % in patients at the emergency ward of the University Hospital of Magdeburg, the capital of Saxony-Anhalt. Our aim is to update these findings in a cohort of healthy blood donors from the same region. Materials and methods The sera of 516 consecutive blood donors (40.1 ± 14.1 years; 286 males and 230 females) were tested for antibodies against H. pylori and CagA. Data on demographics and previous H. pylori eradication therapy were obtained by means of a structured questionnaire. Blood donors with positive serology for H. pylori or CagA and/or history of eradication therapy were classified as H. pylori-positive. Results Overall, 28.9 % of the study cohort were H. pylori-positive. The prevalence was higher in older generations (9 % in 18 – 20 years up to 47 % in 61 – 70 years). In 44.4 % of H. pylori IgG-positive donors, CagA serology was also positive. This proportion was not age-dependent. Study participants with siblings were by trend more often H. pylori-positive (p = 0.066). Conclusion Compared to our previous study in patients at the emergency ward, we found by trend lower age-related H. pylori prevalence rates. In our cohort of healthy blood donors, we confirmed a lower H. pylori prevalence in younger generations.

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Furazolidone- and Nitrofurantoin-ResistantHelicobacter pylori: Prevalence and Role of Genes Involved in Metronidazole Resistance

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.1.306-308.2001 ◽

2001 ◽

Vol 45 (1) ◽

pp. 306-308 ◽

Cited By ~ 43

Author(s):

Dong H. Kwon ◽

Miae Lee ◽

J. J. Kim ◽

J. G. Kim ◽

F. A. K. El-Zaatari ◽

...

Keyword(s):

Helicobacter Pylori ◽

Clinical Isolates ◽

Metronidazole Resistance ◽

H Pylori

ABSTRACT The prevalence of furazolidone, nitrofurantoin, and metronidazole resistance among Helicobacter pylori strains was assessed with 431 clinical isolates. Fifty-two percent were metronidazole resistant, compared to 2% (7 of 431) with resistance to furazolidone and nitrofurantoin. All seven furazolidone- and nitrofurantoin-resistant isolates were also metronidazole resistant.rdxA, frxA, and fdxB knockouts did not result in furazolidone or nitrofurantoin resistance. These data suggest that furazolidone and nitrofurantoin may be good alternatives to metronidazole for treating H. pylori infection.

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Study on Association between Chronic Idiopathic Urticaria and Helicobacter Pylori Infection in Armed Forces Personnel

Journal of Armed Forces Medical College Bangladesh ◽

10.3329/jafmc.v12i2.41108 ◽

2016 ◽

Vol 12 (2) ◽

pp. 122-126 ◽

Cited By ~ 1

Author(s):

Md Sayeed Hasan ◽

Md Shirajul Islam Khan ◽

Jannatun Nayeem

Keyword(s):

Helicobacter Pylori ◽

Eradication Therapy ◽

Armed Forces ◽

Case Control ◽

Chronic Idiopathic Urticaria ◽

Helicobacter Pylori Infection ◽

Enteric Infection ◽

Clinical Disorder ◽

Serum Igg ◽

H Pylori

Introduction: Chronic Idiopathic Urticaria (CIU) has an estimated prevalence of 35-65% and impacts 15 to 25% of the population at some point in their lives. Studies have shown the possible involvement of Helicobacter pylori (H. pylori) infection in chronic idiopathic urticaria (CIU), but the relationship remains controversial. Objective: To quantitatively assess the association between H. pylori infection and chronic idiopathic urticaria. Materials and Methods: This was a case-control type of analytical study and 100 patients were enrolled fifty patients of CIU fulfilling inclusion criteria with no identifiable cause were taken as case and patients without urticaria were taken as control, attending in the department of Dermatology & Venereology, CMH Dhaka for treatment from May 2015 to Aug 2016. Helicobacter pylori infection was confirmed by serum IgG for H. pylori test. Results: The result showed that H. pylori infection significantly affected a high percentage of patients 30 (60%) with chronic idiopathic urticaria. Male respondents were more positive 16(53.3%) than female 14(46.7%), in the middle aged 31-50 year about 18(60%) and triple drug therapy was successful in 16(53.33%) patients in whom H. pylori was detected. Conclusion: Urticaria is a common clinical disorder with complex triggering factors. Chronic urticaria has provided evidence that enteric infection with H. pylori may induce the disease. In this case control study, it was evident that chronic idiopathic urticaria was associated with positive serum IgG for H. Pylori. A trial of H. pylori eradication therapy may be offered to patients with CIU and evidence of H. pylori infection. Journal of Armed Forces Medical College Bangladesh Vol.12(2) 2016: 122-126

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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 ◽

10.3390/antibiotics10091058 ◽

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.

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

Vojnosanitetski pregled ◽

10.2298/vsp150415127g ◽

2016 ◽

Vol 73 (11) ◽

pp. 1044-1049 ◽

Cited By ~ 3

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.

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