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

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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Surveillance of primary antibiotic resistance of Helicobacter pylori at centres in England and Wales over a six-year period (2000-2005)

Eurosurveillance ◽

10.2807/esm.12.07.00721-en ◽

2007 ◽

Vol 12 (7) ◽

pp. 3-4 ◽

Cited By ~ 30

Author(s):

S A Chisholm ◽

E L Teare ◽

K Davies ◽

R J Owen

Keyword(s):

Helicobacter Pylori ◽

Antibiotic Resistance ◽

Eradication Therapy ◽

England And Wales ◽

North Wales ◽

Key Factor ◽

Male Patients ◽

South East England ◽

H Pylori ◽

Resistance Rates

Antibiotic resistance is a key factor in the failure of Helicobacter pylori eradication therapy, yet few sentinel schemes exist to monitor trends in resistance at local, national or international levels. This study aimed, over a six-year period, to monitor resistance levels of H. pylori in England and Wales to the four antibiotics used in its treatment. A total of 1,310 isolates from Gwynedd in north Wales and from mid-Essex in south-east England were collected from 2000 to 2005 and tested for susceptibilities to metronidazole, clarithromycin, amoxicillin and tetracycline. Overall, metronidazole and clarithromycin resistance rates were 28.6% and 8.3% in Gwynedd and significantly higher (36.3%, p=0.0031, and 12.7%, p=0.0112) in mid-Essex. Rates of resistance to metronidazole and clarithromycin increased in both areas over this six-year period. Resistance rates were higher in female compared with male patients (38.1% vs 26.6% for metronidazole, p

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Primary Antimicrobial Susceptibility Changes in Children withHelicobacter pyloriInfection over 13 Years in Northern Italy

Gastroenterology Research and Practice ◽

10.1155/2015/717349 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 7

Author(s):

Marco Manfredi ◽

Pierpacifico Gismondi ◽

Valentina Maffini ◽

Barbara Bizzarri ◽

Fabiola Fornaroli ◽

...

Keyword(s):

Antibiotic Resistance ◽

Antimicrobial Susceptibility ◽

Eradication Therapy ◽

Northern Italy ◽

Local Distribution ◽

Clarithromycin Resistance ◽

Time Period ◽

Metronidazole Resistance ◽

H Pylori ◽

Resistance Rates

The eradication therapy ofHelicobacter pylori(H. pylori) infection is still a challenge for gastroenterologists. One of the main causes of failure inH. pylorieradication is the antibiotic resistance mainly to clarithromycin. Culture from biopsies is maybe the most used method among the antimicrobial susceptibility techniques. In this study, we compared the antimicrobial susceptibility changes in children withH. pyloriinfection over 13 years and we confirmed that clarithromycin resistance has been increased (16% versus 26%) though with no statistically signficant value. Therefore, clarithromycin should not be used in empiric treatment ofH. pylorieradication therapy in children, but its use should be limited only to children with known antimicrobial susceptibility. On the other hand, metronidazole resistance has decreased over this time period in statistically significant manner (56% versus 33%,p=0.014). Furthermore, ampicillin resistance has been confirmed to be very rare (3% versus 0%) in children withH. pyloriinfection. In conclusion, inH. pyloriinfection, if we do not know the antibiotic susceptibility of patients, we should recommend an eradication therapy based on the local distribution of antibiotic resistance rates trying to limit the therapeutic failures.

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Rifamycin use for treatment of Helicobacter pylori infection: a review of recent data

Future Microbiology ◽

10.2217/fmb-2020-0084 ◽

2020 ◽

Vol 15 (12) ◽

pp. 1185-1196 ◽

Cited By ~ 1

Author(s):

Lyudmila Boyanova ◽

Rumyana Markovska ◽

Petyo Hadzhiyski ◽

Nayden Kandilarov ◽

Ivan Mitov

Keyword(s):

Helicobacter Pylori ◽

Adverse Effects ◽

Treatment Options ◽

Eradication Therapy ◽

Multidrug Resistant ◽

Helicobacter Pylori Eradication ◽

Promising Treatment ◽

Third Line ◽

H Pylori ◽

Resistance Rates

Helicobacter pylori eradication has become increasingly challenging. We focused on recent data about rifamycin resistance and rifamycin-containing regimens. Rifampin (rifampicin) resistance rates were <1–18.8% (often ≤7%), while those to rifabutin were 0–<4%. To detect rifabutin resistance by rifampin, 4 mg/l breakpoint was suggested. Eradication success by rifaximin-based regimens was disappointing (<62%), while that of rifabutin-containing regimens was 54.5–>96%, reaching >81% in four studies. Some newer rifamycin analogs like TNP-2092 need further investigation. Briefly, although rifabutin-based regimens carry a risk of adverse effects or increasing mycobacterial resistance, they may be a rational choice for some multidrug-resistant H. pylori strains and as a third-line eradication therapy. Bismuth addition to rifabutin-based therapy and combined rifabutin-containing capsules (Talicia) are promising treatment options.

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Effect of Temperature on Metronidazole Resistance in Helicobacter pylori

Frontiers in Microbiology ◽

10.3389/fmicb.2021.681911 ◽

2021 ◽

Vol 12 ◽

Author(s):

Meiliang Gong ◽

Yingjie Han ◽

Xuning Wang ◽

Hongjin Tao ◽

Fansen Meng ◽

...

Keyword(s):

Helicobacter Pylori ◽

Rna Sequencing ◽

Eradication Therapy ◽

Differentially Expressed ◽

Effect Of Temperature ◽

Resistance Change ◽

Prolonged Incubation ◽

Increased Temperature ◽

Metronidazole Resistance ◽

H 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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Antibacterial resistance in Helicobacter pylori strains isolated from Bulgarian children and adult patients over 9 years

Journal of Medical Microbiology ◽

10.1099/jmm.0.46208-0 ◽

2006 ◽

Vol 55 (1) ◽

pp. 65-68 ◽

Cited By ~ 21

Author(s):

Lyudmila Boyanova ◽

Rossen Nikolov ◽

Elena Lazarova ◽

Galina Gergova ◽

Nikolai Katsarov ◽

...

Keyword(s):

Helicobacter Pylori ◽

Treatment Resistance ◽

Post Treatment ◽

Dilution Method ◽

Agar Dilution Method ◽

Antibacterial Resistance ◽

Primary Resistance ◽

Metronidazole Resistance ◽

H Pylori ◽

Resistance Rates

The aim of this study was to evaluate the primary, combined and post-treatment antibacterial resistance rates in 1205 Helicobacter pylori strains from non-treated (786 adults, 282 children) and treated (109 adults, 28 children) patients in Bulgaria. Susceptibility was tested by the limited agar dilution method. Overall primary resistance rates to metronidazole, clarithromycin, amoxicillin, tetracycline and both metronidazole and clarithromycin were respectively 15·0, 12·5, 1·5, 3·4 and 4·7 % in children and 25·6, 12·6, 0·8, 5·2 and 4·9 % in adults. Primary metronidazole resistance in adults was more common than in children, but the differences for other agents tested were not significant. Primary resistance rates were in the range of those reported worldwide. There was no significant increase in primary resistance rates from 1996/1999 to 2003/2004; however, clarithromycin resistance rates exhibited a slight tendency to increase. Post-treatment resistance to amoxicillin was detected in 1·6 % of 63 strains. Post-treatment resistance to metronidazole was common (81·6 %) and that to clarithromycin was considerable (36 %). Alarming emergence of strains with triple resistance to amoxicillin, metronidazole and clarithromycin was found in two non-treated and three treated patients. The results motivate a larger and continuing surveillance of H. pylori resistance in Bulgaria and worldwide.

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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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