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Rocha GR, Lemos FFB, Silva LGDO, Luz MS, Correa Santos GL, Rocha Pinheiro SL, Calmon MS, de Melo FF. Overcoming antibiotic-resistant Helicobacter pylori infection: Current challenges and emerging approaches. World J Gastroenterol 2025; 31:102289. [PMID: 40093672 PMCID: PMC11886534 DOI: 10.3748/wjg.v31.i10.102289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 11/28/2024] [Accepted: 01/17/2025] [Indexed: 02/26/2025] Open
Abstract
Recent studies have shown a noticeable increase in global Helicobacter pylori (H. pylori) resistance, with clarithromycin resistance surpassing 15% in various areas. However, inadequate epidemiological monitoring, especially in developing countries, and the absence of uniform testing methods lead to discrepancies between regions and a possible underestimation of resistance levels. The complexity of treating H. pylori is driven by its highly dynamic genome, which is prone to frequent mutations contributing to phenotypical resistance. The usual course of action in empirical treatment involves using a combination of various drugs simultaneously, leading to significant resistance selection pressure and potential side effects. The emergence of H. pylori strains resistant to multiple drugs is closely tied to failures in first-line treatment, highlighting the need to prevent further resistance by using optimal initial empirical therapy or regimens guided by antibiotic susceptibility testing, requiring a collection of mixed samples and multiple isolates for accurate assessment. The emergence of new treatments like potassium-competitive acid blockers offers a hopeful approach to decrease antimicrobial usage while still ensuring effectiveness in comparison to traditional therapies with proton pump inhibitors. Additionally, the use of probiotics is under investigation to identify specific strains and formulations that may mitigate therapy-associated adverse effects.
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Affiliation(s)
- Gabriel Reis Rocha
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Fabian Fellipe Bueno Lemos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | | | - Marcel Silva Luz
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Gabriel Lima Correa Santos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Samuel Luca Rocha Pinheiro
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Mariana Santos Calmon
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
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Al Qady A, Aldhaleei W, Salih M, Ali M, Menakuru S, Nayar KD, Wang Z, Stancampiano FF, Harris D, Bi Y. Accuracy of Fecal Polymerase Chain Reaction Testing in Clarithromycin-Resistant Helicobacter Pylori: A Systematic Review and Meta-Analysis. Clin Transl Gastroenterol 2025; 16:e00792. [PMID: 39620581 PMCID: PMC11845177 DOI: 10.14309/ctg.0000000000000792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 11/09/2024] [Indexed: 12/21/2024] Open
Abstract
INTRODUCTION The increasing prevalence of clarithromycin (CLA)-resistant Helicobacter pylori(H. pylori) strains poses a significant challenge in the management of H. pylori infections. This systematic review and meta-analysis investigates the diagnostic accuracy of polymerase chain reaction (PCR) in identifying CLA-resistant H. pylori strains in stool. METHODS A comprehensive literature search was conducted using PubMed, Embase, and Cochrane databases from database inception to April 30, 2023. Eligible studies evaluated the effectiveness of PCR stool tests in detecting CLA-resistant H. pylori strains in adults (>18-year-old). Studies of pediatric populations, alternative methods to PCR or stool samples, and reference tests other than gastric biopsy were excluded. The bivariate random-effects model was used to pool diagnostic accuracy from the included studies. RESULTS The analysis of 11 prospective diagnostic studies with a total of 866 patients showed a pooled sensitivity of 0.97 (95% CI: 0.9-0.99) and a pooled specificity of 0.98 (95% CI: 0.81-1.00). Subgroup analysis based on the used technique demonstrated consistent findings without notable variations. The diagnostic odds ratio was calculated at 1843.92 (95% CI: 134.28-25,321.3). The positive likelihood ratio was determined as 51.02 (95% CI: 4.61-564.5), while the negative likelihood ratio was found to be 0.03 (95% CI: 0.01-0.1). DISCUSSION PCR testing for clarithromycin-resistant H. pylori was highly sensitive and specific across studies with proven reliability in clinical practice, particularly in outpatient settings. Their implementation offers cost-effectiveness and the potential for tailored treatment strategies, holding promise for improved patient outcomes.
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Affiliation(s)
- Ahmed Al Qady
- School of Medicine, Indiana University, Muncie, Indiana, USA
| | - Wafa Aldhaleei
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | | | - Marriam Ali
- School of Medicine, Indiana University, Muncie, Indiana, USA
| | | | - Kapil Dev Nayar
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Zhen Wang
- Health Care Policy and Research, Mayo Clinic, Rochester, New York, USA
| | | | - Dana Harris
- Department of Medicine, Mayo Clinic, Jacksonville, Florida, USA
| | - Yan Bi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
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Yamaoka Y. Revolution of Helicobacter pylori treatment. J Gastroenterol Hepatol 2024; 39:1016-1026. [PMID: 38414319 DOI: 10.1111/jgh.16526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 02/07/2024] [Indexed: 02/29/2024]
Abstract
Helicobacter pylori infection is a major global health concern, and its management has witnessed a revolutionary shift with the emergence of antibiotic resistance. In this review, I explore the mechanisms of H. pylori antibiotic resistance and highlight the critical need for susceptibility-based eradication treatments. The increasing prevalence of antibiotic-resistant strains requires innovative approaches to combat this resilient pathogen. I also delve into the importance of mass screening as a preventive strategy for early detection and intervention, describing my experience in Bhutan. Additionally, I explore promising alternatives, such as vaccination. The aim of this review is to provide insight into the evolving landscape of H. pylori treatment and highlight the need for a paradigm shift in the approach to combating this persistent bacterial infection.
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Grants
- DK62813 NIH HHS
- DK62813 NIH HHS
- 22H02871 Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan
- 21H00346 Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan
- 19H03473 Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan
- 18KK0266 Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan
- Japan Agency for Medical Research and Development
- Japan International Cooperation Agency
- Thailand Science Research and Innovation Fundamental Fund
- Bualuang ASEAN Chair Professorship at Thammasat University
- Center of Excellence in Digestive Diseases, Thammasat University
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Affiliation(s)
- Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
- The Research Center for GLOBAL and LOCAL Infectious Diseases (RCGLID), Oita University, Yufu, Japan
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas, USA
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya, Indonesia
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Amiot A, Hacoon J, Heluwaert F, Mion F, Lamarque D, Moussata D, Mimouni M, Delchier JC, Durand-Zaleski I, Audureau E, Bastuji-Garin S. 14-day tailored PCR-guided triple therapy versus 14-day non-Bismuth concomitant quadruple therapy for Helicobacter pylori eradication: A multicenter, open-label randomized noninferiority controlled trial. Helicobacter 2024; 29:e13076. [PMID: 38680067 DOI: 10.1111/hel.13076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Revised: 03/27/2024] [Accepted: 04/02/2024] [Indexed: 05/01/2024]
Abstract
BACKGROUND The systematic use of susceptibility testing and tailored first-line treatment for Helicobacter pylori eradication has yet to be established. AIM To compare 14-day tailored PCR-guided triple therapy to 14-day non-Bismuth concomitant quadruple therapy for first-line Helicobacter pylori eradication. PATIENTS AND METHODS We performed a multicenter, parallel-group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14-day tailored PCR-guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14-day non-Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication. RESULTS We screened 991 patients for eligibility and randomized 241 patients. The first-line eradication rate was 99.2% in the tailored PCR-guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at -0.68%). Both first-line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR-guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR-guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population. CONCLUSION In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14-day tailored PCR-guided triple therapy as a first-line H. pylori eradication therapy compared to 14-day non-Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236).
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Affiliation(s)
- Aurelien Amiot
- AP-HP, Hôpital Henri Mondor, Department of Gastroentérology, Universite Paris Est Creteil (UPEC), Creteil, France
| | - Jérémy Hacoon
- AP-HP, Hôpital Henri Mondor, Department of Public Health and Clinical Research Unit (URC-Mondor), Cepia, IMRB, Créteil, France
| | - Frederic Heluwaert
- Service Hépatogastro-entérologie, Centre Hospitalier Annecy Genevois, Annecy, France
| | - François Mion
- Hospices Civils de Lyon, Department of Digestive Physiology, Université Lyon I, Inserm U1032, LabTAU, Lyon, France
| | - Dominique Lamarque
- AP-HP, Department of Hepato-Gastroenterology, Ambroise-Pare Hospital, Paris Saclay University, University of Versailles Saint-Quentin-en-Yvelines, INSERM, Infection and Inflammation, Paris, France
| | - Driffa Moussata
- Department of Hepato-Gastroenterology, University Hospital of Tours, Tours, France
| | - Maroua Mimouni
- AP-HP, Paris Health Economics and Health Services Research Unit, URC Eco IdF, Hotel Dieu, 1 Place du Parvis Notre Dame, Paris, France
- Digestive Physiology, Hospices Civils de Lyon, Université de Lyon, Lyon, France
| | - Jean-Charles Delchier
- AP-HP, Hôpital Henri Mondor, Department of Gastroentérology, Universite Paris Est Creteil (UPEC), Creteil, France
| | - Isabelle Durand-Zaleski
- AP-HP, Paris Health Economics and Health Services Research Unit, URC Eco IdF, Hotel Dieu, 1 Place du Parvis Notre Dame, Paris, France
- Digestive Physiology, Hospices Civils de Lyon, Université de Lyon, Lyon, France
| | - Etienne Audureau
- AP-HP, Hôpital Henri Mondor, Department of Public Health and Clinical Research Unit (URC-Mondor), Cepia, IMRB, Créteil, France
| | - Sylvie Bastuji-Garin
- AP-HP, Hôpital Henri Mondor, Department of Public Health and Clinical Research Unit (URC-Mondor), Cepia, IMRB, Créteil, France
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Hasanuzzaman M, Bang CS, Gong EJ. Antibiotic Resistance of Helicobacter pylori: Mechanisms and Clinical Implications. J Korean Med Sci 2024; 39:e44. [PMID: 38288543 PMCID: PMC10825452 DOI: 10.3346/jkms.2024.39.e44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 12/29/2023] [Indexed: 02/01/2024] Open
Abstract
Helicobacter pylori is a pathogenic bacterium associated with various gastrointestinal diseases, including chronic gastritis, peptic ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. The increasing rates of H. pylori antibiotic resistance and the emergence of multidrug-resistant strains pose significant challenges to its treatment. This comprehensive review explores the mechanisms underlying the resistance of H. pylori to commonly used antibiotics and the clinical implications of antibiotic resistance. Additionally, potential strategies for overcoming antibiotic resistance are discussed. These approaches aim to improve the treatment outcomes of H. pylori infections while minimizing the development of antibiotic resistance. The continuous evolution of treatment perspectives and ongoing research in this field are crucial for effectively combating this challenging infection.
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Affiliation(s)
- Md Hasanuzzaman
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Eun Jeong Gong
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea.
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Mommersteeg MC, Nieuwenburg SAV, Wolters LMM, Roovers BHCM, van Vuuren HAJ, Verhaar AP, Bruno MJ, Kuipers EJ, Peppelenbosch MP, Spaander MCW, Fuhler GM. The use of non-invasive stool tests for verification of Helicobacter pylori eradication and clarithromycin resistance. United European Gastroenterol J 2023; 11:894-903. [PMID: 37854002 PMCID: PMC10637120 DOI: 10.1002/ueg2.12473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 08/24/2023] [Indexed: 10/20/2023] Open
Abstract
BACKGROUND Clarithromycin resistance of Helicobacter pylori (H. pylori) represents a major challenge in eradication therapy. In this study, we assessed if non-invasive stool tests can be used to verify successful H. pylori eradication and determine clarithromycin resistance. MATERIALS AND METHODS In this prospective study, patients undergoing urea breath testing (UBT) for confirmation of H. pylori eradication were asked to collect the stool as both a dry fecal sample and fecal immunochemical test (FIT). Stool H. pylori antigen testing (SAT) was performed on these samples and assessed for its accuracy in eradication verification. Type and duration of antibiotic treatment were retrospectively collected from patient records and compared with clarithromycin resistance determined by PCR of stool samples. RESULTS H. pylori eradication information was available for a total of 145 patients (42.7% male, median age: 51.2). Successful eradication was achieved in 68.1% of patients. SAT on FIT samples had similar accuracy for eradication assessment compared to dry fecal samples, 72.1% [95% CI 61.4-81.2] versus 72.2% [95% CI 60.9-81.7]. Clarithromycin resistance rate was 13.4%. CONCLUSION H. pylori antigen testing on FIT stool samples to verify H. pylori eradication is feasible and has similar accuracy as H. pylori antigen testing on dry stool samples. Dry stool, but not FIT, was suitable for non-invasive identification of H. pylori clarithromycin resistance by rt-PCR personalizing antibiotic treatment strategies without the need for invasive diagnostics is desirable, as the cure rate of first-line empirical H. pylori treatment remains low.
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Affiliation(s)
- Michiel C. Mommersteeg
- Department of Gastroenterology and HepatologyErasmus MC University Medical CenterRotterdamThe Netherlands
| | - Stella A. V. Nieuwenburg
- Department of Gastroenterology and HepatologyErasmus MC University Medical CenterRotterdamThe Netherlands
| | - Leonieke M. M. Wolters
- Department of Gastroenterology and HepatologyAlbert Schweitzer HospitalDordrechtThe Netherlands
| | - Buddy H. C. M. Roovers
- Department of Gastroenterology and HepatologyErasmus MC University Medical CenterRotterdamThe Netherlands
| | - Hanneke A. J. van Vuuren
- Department of Gastroenterology and HepatologyErasmus MC University Medical CenterRotterdamThe Netherlands
| | - Auke P. Verhaar
- Department of Gastroenterology and HepatologyErasmus MC University Medical CenterRotterdamThe Netherlands
| | - Marco J. Bruno
- Department of Gastroenterology and HepatologyErasmus MC University Medical CenterRotterdamThe Netherlands
| | - Ernst J. Kuipers
- Department of Gastroenterology and HepatologyErasmus MC University Medical CenterRotterdamThe Netherlands
| | - Maikel P. Peppelenbosch
- Department of Gastroenterology and HepatologyErasmus MC University Medical CenterRotterdamThe Netherlands
| | - Manon C. W. Spaander
- Department of Gastroenterology and HepatologyErasmus MC University Medical CenterRotterdamThe Netherlands
| | - Gwenny M. Fuhler
- Department of Gastroenterology and HepatologyErasmus MC University Medical CenterRotterdamThe Netherlands
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7
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Rosli NA, Al-Maleki AR, Loke MF, Chua EG, Alhoot MA, Vadivelu J. Polymorphism of virulence genes and biofilm associated with in vitro induced resistance to clarithromycin in Helicobacter pylori. Gut Pathog 2023; 15:52. [PMID: 37898785 PMCID: PMC10613384 DOI: 10.1186/s13099-023-00579-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Accepted: 10/19/2023] [Indexed: 10/30/2023] Open
Abstract
BACKGROUND Clarithromycin-containing triple therapy is commonly used to treat Helicobacter pylori infections. Clarithromycin resistance is the leading cause of H. pylori treatment failure. Understanding the specific mutations that occur in H. pylori strains that have evolved antibiotic resistance can help create a more effective and individualised antibiotic treatment plan. However, little is understood about the genetic reprogramming linked to clarithromycin exposure and the emergence of antibiotic resistance in H. pylori. Therefore, this study aims to identify compensatory mutations and biofilm formation associated with the development of clarithromycin resistance in H. pylori. Clarithromycin-sensitive H. pylori clinical isolates were induced to develop clarithromycin resistance through in vitro exposure to incrementally increasing concentration of the antibiotic. The genomes of the origin sensitive isolates (S), isogenic breakpoint (B), and resistant isolates (R) were sequenced. Single nucleotide variations (SNVs), and insertions or deletions (InDels) associated with the development of clarithromycin resistance were identified. Growth and biofilm production were also assessed. RESULTS The S isolates with A2143G mutation in the 23S rRNA gene were successfully induced to be resistant. According to the data, antibiotic exposure may alter the expression of certain genes, including those that code for the Cag4/Cag protein, the vacuolating cytotoxin domain-containing protein, the sel1 repeat family protein, and the rsmh gene, which may increase the risk of developing and enhances virulence in H. pylori. Enhanced biofilm formation was detected among R isolates compared to B and S isolates. Furthermore, high polymorphism was also detected among the genes associated with biofilm production. CONCLUSIONS Therefore, this study suggests that H. pylori may acquire virulence factors while also developing antibiotic resistance due to clarithromycin exposure.
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Affiliation(s)
- Naim Asyraf Rosli
- Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia
| | - Anis Rageh Al-Maleki
- Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
- Department of Medical Microbiology, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, Yemen.
| | - Mun Fai Loke
- Camtech Biomedical Pte Ltd, Singapore, Singapore
| | - Eng Guan Chua
- School of Biomedical Sciences, Marshall Centre for Infectious Disease Research and Training, University of Western Australia, Perth, WA, Australia
| | - Mohammed Abdelfatah Alhoot
- Faculty of Pharmacy, Airlangga University, Surabaya, 60155, Indonesia
- School of Graduate Studies, Management & Science University, Shah Alam, Selangor, Malaysia
| | - Jamuna Vadivelu
- Medical Education Research and Development Unit, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
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Zhang Q, Yang S, Zhou J, Li Z, Wang L, Dong Q. Diagnostic accuracy of stool sample-based PCR in detecting Helicobacter pylori infection: a meta-analysis. J LAB MED 2023; 47:187-197. [DOI: 10.1515/labmed-2023-0004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2025] Open
Abstract
Abstract
The present study was to evaluate the diagnostic accuracy of different types of PCR tests with the aim of determining which one performs best for detecting Helicobacter pylori in stool samples. Related articles were searched from PubMed, Embase, Web of Science databases, Scopus, and Scholar Google. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool and RevMan5.4 software. Pooled sensitivity, specificity, DOR, PLR and NLR for the stool PCR test in detecting H. pylori infection were performed by Stata 15.0 software. Subgroup meta-analysis was performed by Open Meta-analyst software. Ten studies were selected in this study. Stool PCR test had 92.0 % (83.0, 96.0 %) pooled sensitivity, 96.0 % (84.0, 99.0 %) pooled specificity, 296.0 (51.6, 1,696.9) pooled DOR, 26.1 (5.3, 128.7) pooled PLR and 0.09 (0.04, 0.18) NLR in the diagnosis of H. pylori infection, and summary receiver operating characteristic curve (SROC) illustrated an area under the curve (AUC) of 0.98. Subgroup meta-analysis showed rtPCR as having the highest diagnostic accuracy. Our results identify rtPCR as having the highest diagnostic accuracy for the detection of H. pylori in stool samples, and the stool PCR test as a reliable diagnostic tool for H. pylori infection.
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Affiliation(s)
- Qinglong Zhang
- Central Laboratories , Qingdao Municipal Hospital , Qingdao , P.R. China
- Shandong First Medical University , Jinan , P.R. China
| | - Shuang Yang
- Fever Clinic , Qingdao Municipal Hospital , Qingdao , P.R. China
| | - Jianhua Zhou
- Department of Stomatology , Qingdao Municipal Hospital , Qingdao , P.R. China
| | - Zhipeng Li
- Qingdao University , Qingdao , P.R. China
| | - Lili Wang
- Central Laboratories , Qingdao Municipal Hospital , Qingdao , P.R. China
| | - Quanjiang Dong
- Central Laboratories , Qingdao Municipal Hospital , Qingdao , P.R. China
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Jearth V, Rath MM, Chatterjee A, Kale A, Panigrahi MK. Drug-Resistant Helicobacter pylori: Diagnosis and Evidence-Based Approach. Diagnostics (Basel) 2023; 13:2944. [PMID: 37761310 PMCID: PMC10528400 DOI: 10.3390/diagnostics13182944] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 08/25/2023] [Accepted: 09/09/2023] [Indexed: 09/29/2023] Open
Abstract
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.
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Affiliation(s)
- Vaneet Jearth
- Post Graduate Institute Medical Education and Research, Chandigarh 160012, India; (V.J.); (A.C.)
| | | | - Abhirup Chatterjee
- Post Graduate Institute Medical Education and Research, Chandigarh 160012, India; (V.J.); (A.C.)
| | - Aditya Kale
- Tata Memorial Hospital, Mumbai 400012, India;
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10
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Elshenawi Y, Hu S, Hathroubi S. Biofilm of Helicobacter pylori: Life Cycle, Features, and Treatment Options. Antibiotics (Basel) 2023; 12:1260. [PMID: 37627679 PMCID: PMC10451559 DOI: 10.3390/antibiotics12081260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 07/27/2023] [Accepted: 07/28/2023] [Indexed: 08/27/2023] Open
Abstract
Helicobacter pylori is a gastric pathogen that infects nearly half of the global population and is recognized as a group 1 carcinogen by the Word Health Organization. The global rise in antibiotic resistance has increased clinical challenges in treating H. pylori infections. Biofilm growth has been proposed to contribute to H. pylori's chronic colonization of the host stomach, treatment failures, and the eventual development of gastric diseases. Several components of H. pylori have been identified to promote biofilm growth, and several of these may also facilitate antibiotic tolerance, including the extracellular matrix, outer membrane proteins, shifted morphology, modulated metabolism, efflux pumps, and virulence factors. Recent developments in therapeutic approaches targeting H. pylori biofilm have shown that synthetic compounds, such as small molecule drugs and plant-derived compounds, are effective at eradicating H. pylori biofilms. These combined topics highlight the necessity for biofilm-based research in H. pylori, to improve current H. pylori-targeted therapeutic approaches and alleviate relative public health burden. In this review we discuss recent discoveries that have decoded the life cycle of H. pylori biofilms and current biofilm-targeted treatment strategies.
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Affiliation(s)
- Yasmine Elshenawi
- Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA 95064, USA;
| | - Shuai Hu
- Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA 95064, USA;
| | - Skander Hathroubi
- Spartha Medical, CRBS 1 Rue Eugène Boeckel, 67000 Strasbourg, France
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11
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Yu HL, Su DS, Ma SZ, Qi XS. Approaches for detection of antibiotic resistance of Helicobacter pylori: Recent research advances. Shijie Huaren Xiaohua Zazhi 2023; 31:571-576. [DOI: 10.11569/wcjd.v31.i14.571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/18/2023] [Accepted: 07/20/2023] [Indexed: 07/28/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection, a contagious disease, has affected approximately half of the global population. It is associated with the occurrence and development of many diseases, which seriously endangers human public health. Antibiotics play an important role in H. pylori eradication therapy, and the common regimens for H. pylori eradication contain one to three antibiotics. Antibiotic resistance is one of the main reasons for the failure of H. pylori eradication. Detection of antibiotic resistance can be helpful for individualized management, reduction of drug resistance, and improvement of H. pylori eradication. Methods to detect antibiotic resistance of H. pylori primarily consist of traditional drug sensitivity tests and molecular biology methods, such as polymerase chain reaction and its related techniques, DNA sequencing, fluorescence in situ hybridization, and gene chip. This paper reviews the recent advances in approaches for detection of antibiotic resistance of H. pylori.
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Affiliation(s)
- Hong-Lu Yu
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China
- Graduate School of Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Dong-Shuai Su
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China
- The 963rd Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Jiamusi 154000, Heilongjiang Province, China
| | - Shao-Ze Ma
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China
| | - Xing-Shun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China
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12
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Ng HY, Leung WK, Cheung KS. Antibiotic Resistance, Susceptibility Testing and Stewardship in Helicobacter pylori Infection. Int J Mol Sci 2023; 24:11708. [PMID: 37511471 PMCID: PMC10380565 DOI: 10.3390/ijms241411708] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/12/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023] Open
Abstract
Despite the declining trend of Helicobacter pylori (H. pylori) prevalence around the globe, ongoing efforts are still needed to optimize current and future regimens in view of the increasing antibiotic resistance. The resistance of H. pylori to different antibiotics is caused by different molecular mechanisms, and advancements in sequencing technology have come a far way in broadening our understanding and in facilitating the testing of antibiotic susceptibility to H. pylori. In this literature review, we give an overview of the molecular mechanisms behind resistance, as well as discuss and compare different antibiotic susceptibility tests based on the latest research. We also discuss the principles of antibiotic stewardship and compare the performance of empirical therapies based on up-to-date resistance patterns and susceptibility-guided therapies in providing effective H. pylori treatment. Studies and clinical guidelines should ensure that the treatment being tested or recommended can reliably achieve a pre-agreed acceptable level of eradication rate and take into account the variations in antibiotic resistance across populations. Local, regional and international organizations must work together to establish routine antibiotic susceptibility surveillance programs and enforce antibiotic stewardship in the treatment of H. pylori, so that it can be managed in a sustainable and efficient manner.
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Affiliation(s)
- Ho-Yu Ng
- School of Clinical Medicine, The University of Hong Kong, Hong Kong, China
| | - Wai K Leung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
| | - Ka-Shing Cheung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
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13
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Guzman K, Montenegro L, Pazos A. The Helicobacter pylori single nucleotide polymorphisms SNPs associated with multiple therapy resistance in Colombia. Front Microbiol 2023; 14:1198325. [PMID: 37485536 PMCID: PMC10361749 DOI: 10.3389/fmicb.2023.1198325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Accepted: 06/06/2023] [Indexed: 07/25/2023] Open
Abstract
The eradication of Helicobacter pylori (H. pylori) using multiple therapies is used as a prevention strategy. However, its efficacy has been compromised by the emergence of single nucleotide polymorphisms in genes associated with H. pylori's resistance to multiple antibiotics. To estimate antibiotic resistance rates associated with mutations in H. pylori genes in the high-cancer-risk population in Colombia, we included 166 H. pylori whole genome sequences from a cohort of individuals with a high risk of gastric cancer. By using the reference strain ATCC 26695, we identified mutations in specific genes to evaluate resistance rates for different antibiotics: 23S rRNA for clarithromycin, 16S rRNA for tetracycline, pbp1A for amoxicillin, gyrA for levofloxacin, and rdxA for metronidazole. The phylogenomic analysis was conducted using the core genome consisting of 1,594 genes of H. pylori-ATCC 26695. Our findings revealed that the resistance rate of H. pylori to clarithromycin was 3.62%, primarily associated with mutations A2143G and A2142G in the 23S rRNA gene. For tetracycline, the resistance rate was 7.23%, with mutations A926G, A926T, and A928C observed in the 16S rRNA gene. Amoxicillin resistance was found in 25.9% of cases, with observed mutations in the pbp1A gene, including T556S, T593, R649K, R656P, and R656H. In the gyrA gene, mutations N87K, N87I, D91G, D91N, and D91Y were identified, resulting in a resistance rate of 12.04% to levofloxacin. The most common mutations in the rdxA gene associated with metronidazole resistance were a stop codon, and mutations at D59N and D59S, resulting in a resistance rate of 99.3%. The high resistance rate of H. pylori to metronidazole indicated that this drug should be excluded from the eradication therapy. However, the resistance rates for tetracycline and clarithromycin did not exceed the established resistance threshold in Colombia. The increased resistance rate of H. pylori to levofloxacin and amoxicillin may partially explain the observed therapeutic failures in Colombia. The phylogenomic tree showed that the H. pylori isolate belongs to its own lineage (hspColombia). These findings offer valuable insights to enhance the characterization of treatment protocols for the specific H. pylori lineage (hspColombia) at the local level.
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Affiliation(s)
- Kevin Guzman
- Grupo Salud Pública, Centro de Estudios en Salud Universidad de Nariño (CESUN), Universidad de Nariño, Pasto, Colombia
| | - Lidia Montenegro
- Grupo Salud Pública, Centro de Estudios en Salud Universidad de Nariño (CESUN), Universidad de Nariño, Pasto, Colombia
| | - Alvaro Pazos
- Grupo Salud Pública, Centro de Estudios en Salud Universidad de Nariño (CESUN), Universidad de Nariño, Pasto, Colombia
- Departamento de Biología, Universidad de Nariño, Pasto, Colombia
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14
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Kakiuchi T. A true point-of-care molecular testing method for tailored therapy for Helicobacter pylori eradication. Expert Rev Gastroenterol Hepatol 2023; 17:309-310. [PMID: 36765451 DOI: 10.1080/17474124.2023.2179986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/12/2023]
Affiliation(s)
- Toshihiko Kakiuchi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
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15
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Wang Y, Liu L, Liu X, Wu K, Zhu X, Ma L, Su J. An Ultrasensitive PCR-Based CRISPR-Cas13a Method for the Detection of Helicobacter pylori. J Pers Med 2022; 12:jpm12122082. [PMID: 36556302 PMCID: PMC9784247 DOI: 10.3390/jpm12122082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/17/2022] [Accepted: 12/09/2022] [Indexed: 12/23/2022] Open
Abstract
The rapid and simple detection of Helicobacter pylori (H. pylori) is essential for its clinical eradication. Although various methods for detecting H. pylori have been well established, such as endoscopy in combination with histology or culture, rapid urease test (RUT) and molecular tests using clinical specimens, it is of great importance to develop an ultrasensitive and accurate nucleic acid detection platform and apply it to identify H. pylori. To meet these demands, a novel method based on PCR and CRISPR-Cas13a, called PCR-Cas13a, was developed and validated using the DNA of 84 clinical strains and 71 clinical specimens. PCR primers for the pre-amplification of conservative sequence and CRISPR RNA (crRNA) for the detection of specific sequence were designed according to the principle. The designed primers and crRNA were specific to H. pylori, and the assay showed a high degree of specificity compared with other common pathogens. Our detection system can screen H. pylori with a limit of 2.2 copies/μL within 30 mins after PCR amplification. Using a coincidence analysis with traditional methods, our method exhibited 100% accuracy for the detection of H. pylori. Furthermore, its diagnostic performance was compared, in parallel with a q-PCR. The PCR-Cas13a demonstrates 98% sensitivity and 100% specificity. Moreover, our approach had a lower limit of detection (LOD) than q-PCR. Herein, we present a diagnostic system for the highly sensitive screening of H. pylori and distinguish it from other pathogens. All the results demonstrated that this PCR-based CRISPR assay has wide application prospects for the detection of H. pylori and other slow-growth pathogens.
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Affiliation(s)
- Yaxuan Wang
- Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Liyang Liu
- Department of Gastroenterology, Jingdong Medical Area, General Hospital of Chinese PLA, Beijing 101149, China
| | - Xiaochuan Liu
- Department of Gastroenterology, Emergency General Hospital, Beijing 100028, China
| | - Kai Wu
- Department of Gastroenterology, The Eighth Medical Center of PLA General Hospital, Beijing 100091, China
| | - Xiaoyan Zhu
- Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
| | - Liyan Ma
- Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Jianrong Su
- Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
- Correspondence:
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16
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Ansari S, Yamaoka Y. Helicobacter pylori Infection, Its Laboratory Diagnosis, and Antimicrobial Resistance: a Perspective of Clinical Relevance. Clin Microbiol Rev 2022; 35:e0025821. [PMID: 35404105 PMCID: PMC9491184 DOI: 10.1128/cmr.00258-21] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Despite the recent decrease in overall prevalence of Helicobacter pylori infection, morbidity and mortality rates associated with gastric cancer remain high. The antimicrobial resistance developments and treatment failure are fueling the global burden of H. pylori-associated gastric complications. Accurate diagnosis remains the opening move for treatment and eradication of infections caused by microorganisms. Although several reports have been published on diagnostic approaches for H. pylori infection, most lack the data regarding diagnosis from a clinical perspective. Therefore, we provide an intensive, comprehensive, and updated description of the currently available diagnostic methods that can help clinicians, infection diagnosis professionals, and H. pylori researchers working on infection epidemiology to broaden their understanding and to select appropriate diagnostic methods. We also emphasize appropriate diagnostic approaches based on clinical settings (either clinical diagnosis or mass screening), patient factors (either age or other predisposing factors), and clinical factors (either upper gastrointestinal bleeding or partial gastrectomy) and appropriate methods to be considered for evaluating eradication efficacy. Furthermore, to cope with the increasing trend of antimicrobial resistance, a better understanding of its emergence and current diagnostic approaches for resistance detection remain inevitable.
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Affiliation(s)
- Shamshul Ansari
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu City, Oita, Japan
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu City, Oita, Japan
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas, USA
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
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17
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Gareayaghi N, Kocazeybek B. Detection of A2143G, A2142C, and A2142G Point Mutations with Real-Time PCR in Stool Specimens from Children Infected with Helicobacter pylori. Diagnostics (Basel) 2022; 12:2119. [PMID: 36140521 PMCID: PMC9497693 DOI: 10.3390/diagnostics12092119] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/26/2022] [Accepted: 08/29/2022] [Indexed: 11/16/2022] Open
Abstract
Reports have indicated an increasing prevalence of clarithromycin resistance in children relative to adults. Thus, it is important to investigate primary clarithromycin resistance before therapy to avoid treatment failure. A2142G, A2143G, and A2142C point mutations in the peptidyltransferase region of the 23S ribosomal RNA (rRNA) of Helicobacter pylori (H. pylori) strains isolated from children with gastrointestinal symptoms and asymptomatic children were evaluated via real-time polymerase chain reaction (RT-PCR) using fecal DNA samples. The presence of H. pylori was determined using a fecal H. pylori antigen enzyme-linked immunosorbent assay (ELISA) kit from the stools of children (n = 543). A2143G, A2142C, and A2142G point mutations were detected via RT-PCR and confirmed by sequencing the 23S rDNA. Fecal H. pylori antigen testing was positive in 101 symptomatic (49) and asymptomatic (52) children. A significant difference was found between the 0-5- and 5-18-year-old groups in terms of the A2143G and A2142G point mutations (p = 0.001). The A2142C mutation was not detected. There was a significant difference in the A2143G mutation between the symptomatic and asymptomatic 5-18-year-old children (p = 0.019). Macrolides are frequently used to treat upper respiratory tract infections in children due to their selective pressure effect. We suggest that H. pylori strains carrying mutations in the 23S RNA subunit conferring clarithromycin resistance may lead to an intense inflammatory response in the gastric epithelial cells, allowing them to proliferate more rapidly and causing possible diarrhea, halitosis, or abdominal pain in children.
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Affiliation(s)
- Nesrin Gareayaghi
- Istanbul Sisli Hamidiye Etfal Training and Research Hospital, Center for Blood, University of Health Sciences, Istanbul 34098, Turkey
| | - Bekir Kocazeybek
- Department of Medical Microbiology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey
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18
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Fernandez-Caso B, Miqueleiz A, Valdez VB, Alarcón T. Are molecular methods helpful for the diagnosis of Helicobacter pylori infection and for the prediction of its antimicrobial resistance? Front Microbiol 2022; 13:962063. [PMID: 36016780 PMCID: PMC9396220 DOI: 10.3389/fmicb.2022.962063] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 07/18/2022] [Indexed: 11/13/2022] Open
Abstract
Infections produced by Helicobacter pylori (H. pylori), a spiral Gram-negative bacterium, can cause chronic gastritis, peptic ulcer, and gastric cancer. Antibiotic therapy is the most effective treatment for H. pylori infection at present. However, owing to the increasing antibiotic resistance of H. pylori strains, it has become a serious threat to human health. Therefore, the accurate diagnosis of H. pylori infections and its antibiotic resistance markers is of great significance. Conventional microbiological diagnosis of H. pylori is based on culture; however, successful isolation of H. pylori from gastric biopsy specimens is a challenging task affected by several factors and has limitations in terms of the time of response. To improve conventional methods, some molecular techniques, such as PCR, have been recently used in both invasive and non-invasive H. pylori diagnosis, enabling simultaneous detection of H. pylori and point mutations responsible for frequent antibiotic resistance. The advantages and disadvantages of molecular methods, mainly PCR, versus conventional culture for the H. pylori identification and the detection of antibiotic resistance are discussed. As expected, the combination of both diagnostic methods will lead to the most efficient identification of the H. pylori strains and the resistance patterns.
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Affiliation(s)
| | - Ana Miqueleiz
- Department of Microbiology, Hospital Universitario de Navarra, Navarra, Spain
| | - Verónica B. Valdez
- Department of Microbiology, Instituto de Investigación Sanitaria Princesa, Hospital Universitario La Princesa, Madrid, Spain
| | - Teresa Alarcón
- Department of Microbiology, Instituto de Investigación Sanitaria Princesa, Hospital Universitario La Princesa, Madrid, Spain
- *Correspondence: Teresa Alarcón,
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19
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Li H, Shen Y, Song X, Tang X, Hu R, Marshall BJ, Tang H, Benghezal M. Need for standardization and harmonization of Helicobacter pylori antimicrobial susceptibility testing. Helicobacter 2022; 27:e12873. [PMID: 35151236 DOI: 10.1111/hel.12873] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 12/23/2021] [Accepted: 12/27/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIMS As with other infectious diseases, Helicobacter pylori eradication regimens should be guided by susceptibility testing to achieve excellent success rate, especially in the era of high antibiotic resistance. However, susceptibility testing for H. pylori is rarely performed, which can be partly ascribed to the current lack of standardization of testing methods and the lack of unified consensus on the antibiotic resistance breakpoints. The aim of this review was to call for an international consensus on standardization and harmonization of H. pylori susceptibility testing. METHODS We summarize and compare the advantages and disadvantages of four different phenotypic antimicrobial susceptibility testing (AST) methods (agar dilution, E-test, disk diffusion, and broth microdilution) and the molecular susceptibility testing method for H. pylori. RESULTS The standard phenotypic testing methods and the molecular testing methods have their own advantages and disadvantages. Compared to the standard phenotypic methods, the molecular testing method does not require successful H. pylori culture, and therefore, is much more rapid and convenient for clinical use. However, the currently available molecular testing method is only suitable for detecting clarithromycin and quinolone susceptibility profiles in H. pylori. Although the standard AST is time-consuming, it is currently the only way to test the susceptibility of H. pylori to all the commonly used antibiotics. CONCLUSION To make H. pylori susceptibility testing become a clinical routine, an international consensus on standardization and harmonization of H. pylori AST is needed. Future efforts are needed for optimizing broth culture of H. pylori, and developing commercial AST plates for achieving high throughput and automated susceptibility testing for H. pylori.
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Affiliation(s)
- Hong Li
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Yalin Shen
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaona Song
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoqiong Tang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Renwei Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Barry James Marshall
- Helicobacter pylori Research Laboratory, School of Biomedical Sciences, Marshall Centre for Infectious Disease Research and Training, University of Western Australia, Nedlands, Australia
| | - Hong Tang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Mohammed Benghezal
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
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20
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Qiu E, Li Z, Han S. Methods for detection of Helicobacter pylori from stool sample: current options and developments. Braz J Microbiol 2021; 52:2057-2062. [PMID: 34392499 PMCID: PMC8578210 DOI: 10.1007/s42770-021-00589-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 08/03/2021] [Indexed: 01/19/2023] Open
Abstract
Accurate detection of Helicobacter pylori infection and determination of antibiotics have significant meaning in clinical practice. The detection methods can be categorized into two types, invasive and non-invasive, but nowadays we use the urease breath test most frequently which is non-invasive. However, many developing countries cannot meet the requirements for having specialized equipment and they lack trained personnel. Also, for the children, it is difficult to make them cooperate for the test. Methods that detect Helicobacter pylori from stool sample can be a promising alternative for detection used in children and mass screening. Stool antigen tests have several advantages such as rapidity, simplicity, and cheapness, though their results may be influenced by the heterogenicity of antigens, the nature of biochemical techniques, and the amount of antigen presented in the stool. PCR-based methods can specifically detect Helicobacter pylori infection and antibiotic resistance by targeting specific gene sequence, but they also are limited by the requirements of facilities and experts, the existence of inhibitory substance, and interference from the dead bacteria. Some novel methods also deserve our attention. Here we summarized the results of researches about methods using stool sample and we hope our work can help clinicians choose the appropriate test in clinical practice.
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Affiliation(s)
- Enming Qiu
- General Surgery Center, Department of Gastrointestinal Surgery, Zhujiang Hospital, Southern Medical University, Haizhu District, No.253. Gongye Middle Avenue, Guangzhou, Guangdong, 510280 China
| | - Zhou Li
- General Surgery Center, Department of Gastrointestinal Surgery, Zhujiang Hospital, Southern Medical University, Haizhu District, No.253. Gongye Middle Avenue, Guangzhou, Guangdong, 510280 China
| | - Shuai Han
- General Surgery Center, Department of Gastrointestinal Surgery, Zhujiang Hospital, Southern Medical University, Haizhu District, No.253. Gongye Middle Avenue, Guangzhou, Guangdong, 510280 China
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21
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Ru C, Yin L, Tian L, Wang L, Yao Y, Kang L, Li J. Correlation Analysis between the Characteristics of Helicobacter pylori Resistance and the Antibiotic Use Density in a Hospital from 2012 to 2018. JOURNAL OF HEALTHCARE ENGINEERING 2021; 2021:5031667. [PMID: 34804452 PMCID: PMC8601808 DOI: 10.1155/2021/5031667] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 10/11/2021] [Indexed: 01/16/2023]
Abstract
Objective To explore the correlation between the resistance characteristics of Helicobacter pylori (HP) and antibiotic use density (AUD) in a hospital from 2012 to 2018. Methods HP strains isolated from Chinese PLA General Hospital from 2012 to 2018 were collected to analyze the drug resistance of clarithromycin, levofloxacin, amoxicillin, and metronidazole, and their correlation with the AUD of the outpatient department and inpatient department was analyzed, respectively. Results From 2012 to 2018, metronidazole-resistant strains accounted for the largest proportion, followed by clarithromycin and levofloxacin, and amoxicillin-resistant strains accounted for the least. In 2012-2018, the resistance rate of clarithromycin, levofloxacin, amoxicillin, and metronidazole has basically increased year by year; from 2012 to 2018, the highest outpatient AUD in a hospital was amoxicillin, followed by clarithromycin and levofloxacin, metronidazole was the lowest, and the inpatient AUD from high to low was levofloxacin, metronidazole, amoxicillin, and clarithromycin. The drug resistance rate of HP in the hospital from 2012 to 2018 was positively correlated with the AUD of clarithromycin (r = 0.884, P=0.017) and levofloxacin (r = 0.934, P=0.002) in the outpatient department. Conclusions Helicobacter pylori has the strongest resistance to metronidazole and the worst resistance to amoxicillin in the hospital from 2012 to 2018, being related to the intensity of clarithromycin and levofloxacin in the outpatient department. It may provide certain reference significance for the clinical treatment of Helicobacter pylori.
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Affiliation(s)
- Chenglin Ru
- Department of Ultrasound, The Eighth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Li Yin
- Western Medical Distict of Chinese PLA General Hospital, Beijing, China
| | - Lixia Tian
- Department of Emergency Medicine, The Eighth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Lanxiang Wang
- Department of Xiangshan Road Clinic, The Eighth Medical Center, Chinese PLA General Hospital, Xiangshan Road, Beijing, China
| | - Yi Yao
- Department of Gastroenterology, The Eighth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Lin Kang
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Jinping Li
- Department of Xiangshan Road Clinic, The Eighth Medical Center, Chinese PLA General Hospital, Xiangshan Road, Beijing, China
- Department of Gastroenterology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
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22
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Hulten KG, Genta RM, Kalfus IN, Zhou Y, Zhang H, Graham DY. Comparison of Culture With Antibiogram to Next-Generation Sequencing Using Bacterial Isolates and Formalin-Fixed, Paraffin-Embedded Gastric Biopsies. Gastroenterology 2021; 161:1433-1442.e2. [PMID: 34293298 PMCID: PMC9047521 DOI: 10.1053/j.gastro.2021.07.012] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 07/10/2021] [Accepted: 07/14/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The decline in Helicobacter pylori cure rates emphasizes the need for readily available methods to determine antimicrobial susceptibility. Our aim was to compare targeted next-generation sequencing (NGS) and culture-based H pylori susceptibility testing using clinical isolates and paired formalin-fixed, paraffin-embedded (FFPE) gastric biopsies. METHODS H pylori isolates and FFPE tissues were tested for susceptibility to amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifabutin using agar dilution and NGS targeted to 23S rRNA, gyrA, 16S rRNA, pbp1, rpoB and rdxA. Agreement was quantified using κ statistics. RESULTS Paired comparisons included 170 isolates and FFPE tissue for amoxicillin, clarithromycin, metronidazole, and rifabutin and 57 isolates and FFPE tissue for levofloxacin and tetracycline. Agreement between agar dilution and NGS from culture isolates was very good for clarithromycin (κ = 0.90012), good for levofloxacin (κ = 0.78161) and fair for metronidazole (κ = 0.55880), and amoxicillin (κ = 0.21400). Only 1 isolate was resistant to tetracycline (culture) and 1 to rifabutin (NGS). Comparison of NGS from tissue blocks and agar dilution from isolates from the same stomachs demonstrated good accuracy to predict resistance for clarithromycin (94.1%), amoxicillin (95.9%), metronidazole (77%), levofloxacin (87.7%), and tetracycline (98.2%). Lack of resistance precluded comparisons for tetracycline and rifabutin. CONCLUSIONS Compared with agar dilution, NGS reliably determined resistance to clarithromycin, levofloxacin, rifabutin, and tetracycline from clinical isolates and formalin-fixed gastric tissue. Consistency was fair for metronidazole and amoxicillin. Culture-based testing can predict treatment outcomes with clarithromycin and levofloxacin. Studies are needed to compare the relative ability of both methods to predict treatment outcomes for other antibiotics.
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Affiliation(s)
| | - Robert M. Genta
- Inform Diagnostics, Irving, Texas,Department of Pathology, Baylor College of Medicine, Houston, Texas
| | | | - Yi Zhou
- American Molecular Laboratories, Vernon Hills, Illinois
| | - Hongjun Zhang
- American Molecular Laboratories, Vernon Hills, Illinois
| | - David Y. Graham
- Department of Medicine, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, Texas
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23
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Gingold-Belfer R, Niv Y, Schmilovitz-Weiss H, Levi Z, Boltin D. Susceptibility-guided versus empirical treatment for Helicobacter pylori infection: A systematic review and meta-analysis. J Gastroenterol Hepatol 2021; 36:2649-2658. [PMID: 34114673 DOI: 10.1111/jgh.15575] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 05/10/2021] [Accepted: 06/08/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM Empirical therapy for Helicobacter pylori infection is limited by increasing antibiotic resistance and suboptimal eradication rates. Studies of the relative effectiveness of susceptibility-guided therapy have produced conflicting results. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine whether susceptibility-guided therapy is superior to empirical therapy for H. pylori infection. METHODS We searched articles listed in PubMed, MEDLINE, EMBASE, and Web of Science through May 25, 2020, RCTs comparing susceptibility-guided versus empirical therapy for H. pylori infection. Outcomes, including effectiveness and safety, were analyzed in a meta-analysis. RESULTS Our final analysis included 16 studies, comprising 2374 patients who received susceptibility-guided therapy and 2451 patients who received empirical treatment. In previously untreated subjects, susceptibility-guided therapy was slightly more effective than empirical therapy (intent to treat risk ratio [RR], 1.14; 95% confidence interval [CI], 1.07-1.21; P < 0.0001, I2 = 75%). Susceptibility-guided therapy was superior to first-line clarithromycin-based triple therapy only when clarithromycin resistance exceeded 20% (RR, 1.18; 95% CI, 1.07-1.30; P = 0.001, I2 = 81%). Susceptibility-guided therapy was not more effective than empirical quadruple therapy (RR, 1.02; 95% CI, 0.92-1.13; P = 0.759, I2 = 80%). Three RCTs were performed exclusively among previously treated subjects, and were highly heterogeneous. CONCLUSIONS Our findings suggest that susceptibility-guided treatment may be slightly superior to empirical first line triple therapy. Susceptibility- guided treatment does not appear to be superior to empirical first-line quadruple therapy or empirical rescue therapy.
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Affiliation(s)
- Rachel Gingold-Belfer
- Division of Gastroenterology, , Rabin Medical Center, Petah Tikva, Israel.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yaron Niv
- Division of Patient Safety and Quality Improvement, Ministry of Health, Jerusalem, Israel
| | - Hemda Schmilovitz-Weiss
- Division of Gastroenterology, , Rabin Medical Center, Petah Tikva, Israel.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Zohar Levi
- Division of Gastroenterology, , Rabin Medical Center, Petah Tikva, Israel.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Doron Boltin
- Division of Gastroenterology, , Rabin Medical Center, Petah Tikva, Israel.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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24
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White B, Sterrett JD, Grigoryan Z, Lally L, Heinze JD, Alikhan H, Lowry CA, Perez LJ, DeSipio J, Phadtare S. Characterization of gut microbiome and metabolome in Helicobacter pylori patients in an underprivileged community in the United States. World J Gastroenterol 2021; 27:5575-5594. [PMID: 34588753 PMCID: PMC8433610 DOI: 10.3748/wjg.v27.i33.5575] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 07/02/2021] [Accepted: 08/13/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori), a bacterium that infects approximately half of the world's population, is associated with various gastrointestinal diseases, including peptic ulcers, non-ulcer dyspepsia, gastric adenocarcinoma, and gastric lymphoma. As the burden of antibiotic resistance increases, the need for new adjunct therapies designed to facilitate H. pylori eradication and reduce negative distal outcomes associated with infection has become more pressing. Characterization of the interactions between H. pylori, the fecal microbiome, and fecal fatty acid metabolism, as well as the mechanisms underlying these interactions, may offer new therapeutic approaches. AIM To characterize the gut microbiome and metabolome in H. pylori patients in a socioeconomically challenged and underprivileged inner-city community. METHODS Stool samples from 19 H. pylori patients and 16 control subjects were analyzed. 16S rRNA gene sequencing was performed on normalized pooled amplicons using the Illumina MiSeq System using a MiSeq reagent kit v2. Alpha and beta diversity analyses were performed in QIIME 2. Non-targeted fatty acid analysis of the samples was carried out using gas chromatography-mass spectrometry, which measures the total content of 30 fatty acids in stool after conversion into their corresponding fatty acid methyl esters. Multi-dimensional scaling (MDS) was performed on Bray-Curtis distance matrices created from both the metabolomics and microbiome datasets and a Procrustes test was performed on the metabolomics and microbiome MDS coordinates. RESULTS Fecal microbiome analysis showed that alpha diversity was lowest in H. pylori patients over 40 years of age compared to control subjects of similar age group. Beta diversity analysis of the samples revealed significant differences in microbial community structure between H. pylori patients and control subjects across all ages. Thirty-eight and six taxa had lower and higher relative abundance in H. pylori patients, respectively. Taxa that were enriched in H. pylori patients included Atopobium, Gemellaceae, Micrococcaceae, Gemellales and Rothia (R. mucilaginosa). Notably, relative abundance of the phylum Verrucomicrobia was decreased in H. pylori patients compared to control subjects. Procrustes analysis showed a significant relationship between the microbiome and metabolome datasets. Stool samples from H. pylori patients showed increases in several fatty acids including the polyunsaturated fatty acids (PUFAs) 22:4n6, 22:5n3, 20:3n6 and 22:2n6, while decreases were noted in other fatty acids including the PUFA 18:3n6. The pattern of changes in fatty acid concentration correlated to the Bacteroidetes:Firmicutes ratio determined by 16S rRNA gene analysis. CONCLUSION This exploratory study demonstrates H. pylori-associated changes to the fecal microbiome and fecal fatty acid metabolism. Such changes may have implications for improving eradication rates and minimizing associated negative distal outcomes.
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Affiliation(s)
- Brian White
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
| | - John D Sterrett
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, United States
| | - Zoya Grigoryan
- Department of Internal Medicine, Lenox Hill Hospital, NYC, NY 10075, United States
| | - Lauren Lally
- Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, United States
| | - Jared D Heinze
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, United States
| | - Hyder Alikhan
- Department of Biological Sciences, Rowan University, Glassboro, NJ 08028, United States
| | - Christopher A Lowry
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, United States
| | - Lark J Perez
- Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ 08028, United States
| | - Joshua DeSipio
- Department of Gastroenterology, Cooper University Hospital, Camden, NJ 08103, United States
| | - Sangita Phadtare
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
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25
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Akeel M, Elhafey A, Shehata A, Elmakki E, Aboshouk T, Ageely H, Mahfouz MS. Efficacy of immunohistochemical staining in detecting <em>Helicobacter pylori</em> in Saudi patients with minimal and atypical infection. Eur J Histochem 2021; 65. [PMID: 34284564 PMCID: PMC8314390 DOI: 10.4081/ejh.2021.3222] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 05/05/2021] [Indexed: 12/21/2022] Open
Abstract
Gastric Helicobacter pylori infection is diagnosed based on histopathological evaluation of gastric mucosal biopsies, urease test, urea breath test, H. pylori culturing, or direct detection using polymerase chain reaction (PCR). This study aimed to evaluate the efficacy of immunohistochemical (IHC) staining in detecting H. pylori in gastric biopsies from patients with chronic gastritis and minimal or atypical infection. Gastric biopsies from 50 patients with chronic gastritis were subjected to routine haematoxylin and eosin (H-E), modified Giemsa, and IHC staining. The results of staining were compared with those of quantitative real-time PCR (qRT-PCR). The qRT-PCR analysis identified 32 (64%) H. pylori-positive cases, whereas IHC, H-E, and modified Giemsa staining identified 29 (58%), 27 (54%), and 21 (42%) positive cases. The sensitivity of IHC staining (87.50%) was higher than that of H-E (59.38%) and modified Giemsa (43.75%) staining. The specificity of H-E, modified Giemsa, and IHC staining was 55.56%, 61.11%, and 94.44%, respectively. IHC staining exhibited the highest diagnostic accuracy (90%), followed by H-E (58%) and modified Giemsa (50%) staining. Active gastritis, intestinal metaplasia, and lymphoid follicles were detected in 32 (64%), 4 (8%), and 22 (44%) cases, respectively, and all of these cases were H. pylori positive. In contrast to routine H-E and modified Giemsa staining, IHC allows for the accurate H. pylori detection in cases with minimal or atypical infection. Moreover, IHC can be an alternative diagnostic method to qRT-PCR for detection of H. pylori in such cases.
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Affiliation(s)
- Mohammed Akeel
- Department of Anatomy, Faculty of Medicine, Jazan University.
| | - Ahmed Elhafey
- Department of Pathology, Faculty of Medicine, Jazan University.
| | - Atef Shehata
- Department of Microbiology and Immunology, Faculty of Medicine, Jazan University.
| | - Erwa Elmakki
- Department of Internal Medicine, Faculty of Medicine, Jazan University.
| | - Thanaa Aboshouk
- Department of Biochemistry, Faculty of Medicine, Jazan University.
| | - Hussein Ageely
- Department of Internal Medicine, Faculty of Medicine, Jazan University.
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26
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Dore MP, Pes GM. What Is New in Helicobacter pylori Diagnosis. An Overview. J Clin Med 2021; 10:jcm10102091. [PMID: 34068062 PMCID: PMC8152493 DOI: 10.3390/jcm10102091] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 05/05/2021] [Accepted: 05/11/2021] [Indexed: 12/12/2022] Open
Abstract
Helicobacter pylori infection remains one of the most prevalent infections worldwide, especially in low-resource countries, and the major risk factor for peptic ulcer and gastric cancer. The “test-and-treat” strategy is recommended by several guidelines and consensus. The choice of testing method is based on patient age, presence of alarm signs and/or symptoms, use of non-steroidal anti-inflammatory drugs, as well as local availability, test reliability, and cost. Culture is the gold standard to detect H. pylori and, possibly, to perform susceptibility testing, however, it requires upper endoscopy and dedicated labs. Recent advances in molecular biology have provided new strategies in detecting infection and antimicrobial resistance without invasive tests. In this review we attempt to offer a comprehensive panorama on the new diagnostic tools and their potential use in clinical settings, in order to accomplish specific recommendations.
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Affiliation(s)
- Maria Pina Dore
- Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, University of Sassari, 07100 Sassari, Italy;
- Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
- Correspondence: ; Tel.: +39-079-229-886
| | - Giovanni Mario Pes
- Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, University of Sassari, 07100 Sassari, Italy;
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Domanovich-Asor T, Craddock HA, Motro Y, Khalfin B, Peretz A, Moran-Gilad J. Unraveling antimicrobial resistance in Helicobacter pylori: Global resistome meets global phylogeny. Helicobacter 2021; 26:e12782. [PMID: 33491828 DOI: 10.1111/hel.12782] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 12/25/2020] [Accepted: 12/31/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Antimicrobial resistance (AMR) in Helicobacter pylori is increasing globally and can result in treatment failure and inappropriate antibiotic usage. This study used whole genome sequencing (WGS) to conduct an analysis of the H. pylori resistome and phylogeny. MATERIALS/METHODS A total of 1040 H. pylori isolate sequences were retrieved. Analysis was conducted via an in-house bioinformatics pipeline targeting point mutations in selected genes frequently associated with AMR (pbp1A, 23S rRNA, gyrA, rdxA, frxA, and rpoB) and phylogenomic analyses using core genome multilocus sequence typing (cgMLST). RESULTS Phylogenomic analysis revealed a notable geographical clustering of H. pylori genomes across world regions, but large distances of more than 1000 loci between isolates on individual branches were observed. Resistome analysis revealed the prevalence of common mutations which have previously been found to correlate with phenotypic antibiotic resistance; the most common point mutations for each gene were S589G (pbp1A, 48.8% of perfect aligned sequences), A2143G (23S rRNA, 27.4% of perfectly aligned sequences), N87 K\I\Y (gyrA, 14.7% of perfectly aligned sequences), R131K (rdxA, 65.7% of perfectly aligned sequences), and C193S (frxA, 62.6% of perfectly aligned sequences). CONCLUSIONS This is the largest study to date featuring the global phylogeny of H. pylori in conjunction with a global snapshot of the H. pylori resistome based on >1000 genomes. Further analyses that combine WGS and phenotypic methods will provide further understanding of the association between the mutations and resistance.
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Affiliation(s)
- Tal Domanovich-Asor
- MAGICAL Group, Department of Health Systems Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Hillary A Craddock
- MAGICAL Group, Department of Health Systems Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Yair Motro
- MAGICAL Group, Department of Health Systems Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Boris Khalfin
- MAGICAL Group, Department of Health Systems Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Avi Peretz
- Clinical Microbiology Laboratory, Baruch Padeh Medical Center, Poriyah and Azrieli Faculty of Medicine, Bar-Ilan University, Galilee, Israel
| | - Jacob Moran-Gilad
- MAGICAL Group, Department of Health Systems Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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Singh H, Chung H, Awan I, Mone A, Cooper R, Patel S, Grigoryan Z, Ishida Y, Papachristou C, Judge T, DeSipio J, Phadtare S. Designing strategies for eradication of Helicobacter pylori based on prevalence patterns of infection and antibiotic resistance in a low-income, medically underserved community in the United States. Helicobacter 2021; 26:e12769. [PMID: 33167084 DOI: 10.1111/hel.12769] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 10/05/2020] [Accepted: 10/10/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Regional variation in Helicobacter pylori resistance patterns is a significant contributing factor for the ineffectiveness of traditional treatments. To improve treatment outcomes, we sought to create an individualized, susceptibility-driven therapeutic approach among our patient population, which is one of the poorest in the nation. It is medically underserved, minority-predominant and has high incidence of H pylori infection. METHODS We compiled various factors involved in the antibiotic resistance of H pylori from literature. We then created a predictive model to customize therapies based on analyzed data from 2,014 H pylori patients with respect to several of these factors. The predictions of the model were further tested with analysis of patient stool samples. RESULTS A clear pattern of H pylori prevalence and antibiotic resistance was observed in our patients. We observed that majority of H pylori patients were women (62%) and over the age of 40 years (80%). 30% and 36% of the H pylori patients were African American and Hispanic, respectively. A median household income of less than $54,000, past H pylori infection, previous use of certain antibiotics for any infection decreased the chance of eradication. Results of the stool testing were consistent with model predictions (90% accuracy). CONCLUSION This model demonstrates the predictive accuracy of H pylori infection and antibiotic resistance based on patient attributes and previous treatment history. It will be useful to formulate customized treatments with predicted outcomes to minimize failures. Our community attributes may contribute toward broad applicability of model for other similar communities.
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Affiliation(s)
- Harpreet Singh
- Cooper Medical School of Rowan University, Camden, NJ, USA
| | - Hansol Chung
- Cooper Medical School of Rowan University, Camden, NJ, USA
| | - Imad Awan
- Cooper Medical School of Rowan University, Camden, NJ, USA
| | | | - Robert Cooper
- Digestive Disease Associates, LTD, Wyomissing, PA, USA
| | | | | | - Yojiro Ishida
- St Jude children's research hospital, Philadelphia, PA, USA
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30
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Domanovich-Asor T, Motro Y, Khalfin B, Craddock HA, Peretz A, Moran-Gilad J. Genomic Analysis of Antimicrobial Resistance Genotype-to-Phenotype Agreement in Helicobacter pylori. Microorganisms 2020; 9:E2. [PMID: 33374988 PMCID: PMC7822022 DOI: 10.3390/microorganisms9010002] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 12/11/2020] [Accepted: 12/15/2020] [Indexed: 02/07/2023] Open
Abstract
Antimicrobial resistance (AMR) in Helicobacter pylori is increasing and can result in treatment failure and inappropriate antibiotic usage. This study used whole genome sequencing (WGS) to comprehensively analyze the H. pylori resistome and phylogeny in order to characterize Israeli H. pylori. Israeli H. pylori isolates (n = 48) underwent antimicrobial susceptibility testing (AST) against five antimicrobials and WGS analysis. Literature review identified 111 mutations reported to correlate with phenotypic resistance to these antimicrobials. Analysis was conducted via our in-house bioinformatics pipeline targeting point mutations in the relevant genes (pbp1A, 23S rRNA, gyrA, rdxA, frxA, and rpoB) in order to assess genotype-to-phenotype correlation. Resistance rates of study isolates were as follows: clarithromycin 54%, metronidazole 31%, amoxicillin 10%, rifampicin 4%, and levofloxacin 2%. Genotype-to-phenotype correlation was inconsistent; for every analyzed gene at least one phenotypically susceptible isolate was found to have a mutation previously associated with resistance. This was also observed regarding mutations commonly used in commercial kits to diagnose AMR in H. pylori cases. Furthermore, 11 novel point mutations associated with a resistant phenotype were detected. Analysis of a unique set of H. pylori isolates demonstrates that inferring resistance phenotypes from WGS in H. pylori remains challenging and should be optimized further.
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Affiliation(s)
- Tal Domanovich-Asor
- MAGICAL Group, Department of Health Systems Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel; (T.D.-A.); (Y.M.); (B.K.); (H.A.C.)
| | - Yair Motro
- MAGICAL Group, Department of Health Systems Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel; (T.D.-A.); (Y.M.); (B.K.); (H.A.C.)
| | - Boris Khalfin
- MAGICAL Group, Department of Health Systems Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel; (T.D.-A.); (Y.M.); (B.K.); (H.A.C.)
| | - Hillary A. Craddock
- MAGICAL Group, Department of Health Systems Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel; (T.D.-A.); (Y.M.); (B.K.); (H.A.C.)
| | - Avi Peretz
- Clinical Microbiology Laboratory, Baruch Padeh Medical Center, Poriyah and Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel;
| | - Jacob Moran-Gilad
- MAGICAL Group, Department of Health Systems Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel; (T.D.-A.); (Y.M.); (B.K.); (H.A.C.)
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Egli K, Wagner K, Keller PM, Risch L, Risch M, Bodmer T. Comparison of the Diagnostic Performance of qPCR, Sanger Sequencing, and Whole-Genome Sequencing in Determining Clarithromycin and Levofloxacin Resistance in Helicobacter pylori. Front Cell Infect Microbiol 2020; 10:596371. [PMID: 33392106 PMCID: PMC7773895 DOI: 10.3389/fcimb.2020.596371] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 11/17/2020] [Indexed: 12/21/2022] Open
Abstract
Helicobacter pylori antibiotic resistance is increasing worldwide, emphasizing the urgent need for more rapid resistance detection prior to the administration of H. pylori eradication regimens. Macrolides and fluoroquinolones are widely used to treat H. pylori. In this study, we aimed to compare the diagnostic performance of A) 23SrDNA qPCR (with melting curve analysis) and an in-house developed gyrA qPCR followed by Sanger sequencing with a commercial IVD-marked hybridization probe assay (for 23SrDNA and gyrA) using 142 gastric biopsies (skipping culturing) and B) the same two qPCR for 23SrDNA and gyrA (including Sanger sequencing) with whole-genome sequencing (WGS) and phenotypic characterization of clarithromycin and levofloxacin resistance using 76 cultured isolates. The sensitivity of both qPCRs was 100% compared to that of the commercial IVD-marked hybridization probe assay for the detection of H. pylori in gastric biopsies (without resistance testing). The specificity of the qPCR gyrA followed by Sanger sequencing was 100%, indicating that the best sequence identity was always H. pylori. The results show good agreement between molecular tests, especially between qPCR (inclusive Sanger sequencing) and WGS. Discrepancies (concerning mutated or wild type of positive H. pylori gastric biopsies) were observed between Sanger sequencing of the gyrA gene and the corresponding commercial hybridization probe assay, mostly because the high sequence diversity of the gyrA gene even at positions adjacent to the relevant codons of 87 and 91 interfered with obtaining correct results from the hybridization probe assay. Interestingly, we found several mixed sequences, indicating mixed populations in the gastric biopsies (direct detection without culturing). There was a high percentage of both levofloxacin and clarithromycin resistance in gastric biopsies (both between 22% and 29%, direct detection in gastric biopsies). Therefore, we recommend analyzing both targets in parallel. We confirmed that phenotypic resistance is highly correlated with the associated mutations. We concluded that the two qPCR followed by Sanger sequencing of the gyrA gene is a fast, cost-effective and comprehensive method for resistance testing of H. pylori directly in gastric biopsies.
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Affiliation(s)
- Konrad Egli
- Labormedizinisches zentrum Dr Risch, Buchs, Switzerland
| | - Karoline Wagner
- Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.,Laboratory Medicine, University Hospital of Basel, Basel, Switzerland
| | - Peter M Keller
- Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.,Institute for Infectious Diseases, University of Bern, Bern, Switzerland
| | - Lorenz Risch
- Labormedizinisches zentrum Dr Risch, Buchs, Switzerland.,Private University of the Principality of Liechtenstein, Triesen, Liechtenstein
| | - Martin Risch
- Labormedizinisches zentrum Dr Risch, Buchs, Switzerland
| | - Thomas Bodmer
- Labormedizinisches zentrum Dr Risch, Buchs, Switzerland
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Yusibova M, Hasman H, Clausen PTLC, Imkamp F, Wagner K, Andersen LP. CRHP Finder, a webtool for the detection of clarithromycin resistance in Helicobacter pylori from whole-genome sequencing data. Helicobacter 2020; 25:e12752. [PMID: 32844531 DOI: 10.1111/hel.12752] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 07/08/2020] [Accepted: 07/22/2020] [Indexed: 01/23/2023]
Abstract
BACKGROUND Resistance to clarithromycin in Helicobacter pylori (H pylori) is mediated by mutations in the domain V of the 23S rRNA gene (A2142G, A2143G, A2142C). Other polymorphisms in the 23S rRNA gene have been reported to cause low-level clarithromycin resistance but their importance is still under debate. In this study, we aimed to develop and evaluate the CRHP Finder webtool for detection of the most common mutations mediating clarithromycin resistance from whole-genome sequencing (WGS) data. Moreover, we included an analysis of 23 H pylori strains from Danish patients between January 2017 and September 2019 in Copenhagen, Denmark. MATERIALS AND METHODS The CRHP Finder detects the fraction of each of the four nucleotides in nucleotide positions 2142, 2143, 2182, 2244 and 2712 of the 23S rRNA gene in H pylori (E coli numbering) by aligning raw sequencing reads (fastq format) with k-mer alignment (KMA). The nucleotide distribution in each position is compared to previously described point mutations mediating clarithromycin resistance in H pylori, and a genotypic prediction of the clarithromycin resistance phenotype is presented as output. For validation of the CRHP webtool, 137 fastq paired-end sequencing datasets originating from a well-characterized strain collection of H pylori were analyzed. RESULTS The CRHP Finder correctly identified all resistance mutations reported in the sequencing data of 137 H pylori strains. In the 23 Danish H pylori strains, CRHP Finder detected A2143G (13%) in all resistant strains, and T2182C (13%) and C2244T (4,3%) nucleotide exchanges in only susceptible strains. CONCLUSION In this study, we present the validation of the first webtool for H pylori resistance prediction based on the detection of 23S rRNA mutations (A2142C, A2142G, A2143G, T2182C, C2244T, T2712C) from WGS data of H pylori.
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Affiliation(s)
- Melodi Yusibova
- Department of Clinical Microbiology, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark
| | - Henrik Hasman
- Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark
| | | | - Frank Imkamp
- Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland
| | - Karoline Wagner
- Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.,Clinical Virology Division, University Hospital Basel, Basel, Switzerland
| | - Leif Percival Andersen
- Department of Clinical Microbiology, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark
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Yin G, Bie S, Gu H, Shu X, Zheng W, Peng K, Zhao H, Li F, Chen B, Botchway BOA, Fang M, Jiang M. Application of gene chip technology in the diagnostic and drug resistance detection of Helicobacter pylori in children. J Gastroenterol Hepatol 2020; 35:1331-1339. [PMID: 31930581 DOI: 10.1111/jgh.14980] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 10/08/2019] [Accepted: 01/05/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Helicobacter pylori (HP) culture for diagnosing HP infection is time-consuming and technologically complex. This study evaluated the clinical significance of gastric mucosal gene chip technology in the rapid diagnosis of HP infection and detection of drug resistance in children. METHODS Patients (between the age of 2.5 and 16.0 years old) manifesting gastrointestinal symptoms were enrolled in this study. HP culture of gastric mucosa and drug sensitivity test were performed. A gene chip of gastric mucosa was used to detect the presence of HP infection, some single nucleotide polymorphisms in HP drug resistance genes, or associated gene mutation. DNA sequencing was investigated and compared with the gene chip test results. RESULTS Out of 267 cases, HP culture was positive in 169 cases and negative in 98 cases. HP detection by the gene chip method was positive in 208 cases and negative in 59 cases. The sensitivity, specificity, and accuracy of the gene chip technology for diagnosing HP infection were 96.1, 85.0, and 93.6%, respectively. HP resistance gene locus using the gene chip showed the main mutation locus of clarithromycin to be 2143A/G, levofloxacin at locus GyrA 91 and GyrA 87, and amoxicillin at PBP1 556ser. Concordance rates between gene chip and DNA sequencing for VacA-S/M, 16S rRNA, 23S rRNA, and GyrA were greater than 95%, and that of PBP1 was greater than 82%. CONCLUSION Gastric mucosal gene chip technology can be used for rapid diagnosis and drug resistance detection of HP infection in children.
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Affiliation(s)
- Guofeng Yin
- Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.,Department of Pediatrics, Shaoxing Women and Children's Hospital, Shaoxing, China
| | - Shuxian Bie
- Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Hongdan Gu
- Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Xiaoli Shu
- Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Wei Zheng
- Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Kerong Peng
- Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Hong Zhao
- Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Fubang Li
- Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Bo Chen
- Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Benson O A Botchway
- Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, China
| | - Marong Fang
- Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, China
| | - Mizu Jiang
- Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
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Abstract
PURPOSE OF REVIEW Helicobacter pylori eradication has become more challenging over the past decade due to increasing antimicrobial resistance, especially to clarithromycin and levofloxacin. We identified 508 recent publications on H. pylori treatment (published between January 2018 and June 2019), focusing on the most highly clinically relevant for this review. RECENT FINDINGS Declining H. pylori eradication rates with clarithromycin triple therapy have led to most guidelines recommending 14 days bismuth-based quadruple therapy or concomitant therapy as the best initial empiric regimen. Substituting amoxicillin for tetracycline or metronidazole in quadruple therapy, and a three-in-one pill version of the regimen, also appear effective. Vonoprazan, a potent acid inhibitor, can overcome much clarithromycin resistance in triple therapy. High-dose dual therapy (proton pump inhibitor with amoxicillin) is a promising alternative approach. Reviewing resistance patterns to select suitable first-line empiric therapies is important in high resistance regions. Molecular methods to evaluate H. pylori antimicrobial susceptibility promise to be simpler than standard microbiological culture. The cost-effectiveness of antimicrobial susceptibility testing in refractory cases remains unproven. SUMMARY Updating clinicians treating H. pylori is important to combat the emerging problems of multidrug antimicrobial resistance in H. pylori strains. Truly novel approaches to H. pylori eradication are needed.
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Pohl D, Keller PM, Bordier V, Wagner K. Review of current diagnostic methods and advances in Helicobacter pylori diagnostics in the era of next generation sequencing. World J Gastroenterol 2019; 25:4629-4660. [PMID: 31528091 PMCID: PMC6718044 DOI: 10.3748/wjg.v25.i32.4629] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 06/25/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is highly prevalent in the human population and may lead to severe gastrointestinal pathology including gastric and duodenal ulcers, mucosa associated tissue lymphoma and gastric adenocarcinoma. In recent years, an alarming increase in antimicrobial resistance and subsequently failing empiric H. pylori eradication therapies have been noted worldwide, also in many European countries. Therefore, rapid and accurate determination of H. pylori’s antibiotic susceptibility prior to the administration of eradication regimens becomes ever more important. Traditionally, detection of H. pylori and its antimicrobial resistance is done by culture and phenotypic drug susceptibility testing that are cumbersome with a long turn-around-time. Recent advances in diagnostics provide new tools, like real-time polymerase chain reaction (PCR) and line probe assays, to diagnose H. pylori infection and antimicrobial resistance to certain antibiotics, directly from clinical specimens. Moreover, high-throughput whole genome sequencing technologies allow the rapid analysis of the pathogen’s genome, thereby allowing identification of resistance mutations and associated antibiotic resistance. In the first part of this review, we will give an overview on currently available diagnostic methods for detection of H. pylori and its drug resistance and their implementation in H. pylori management. The second part of the review focusses on the use of next generation sequencing technology in H. pylori research. To this end, we conducted a literature search for original research articles in English using the terms “Helicobacter”, “transcriptomic”, “transcriptome”, “next generation sequencing” and “whole genome sequencing”. This review is aimed to bridge the gap between current diagnostic practice (histology, rapid urease test, H. pylori culture, PCR and line probe assays) and new sequencing technologies and their potential implementation in diagnostic laboratory settings in order to complement the currently recommended H. pylori management guidelines and subsequently improve public health.
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Affiliation(s)
- Daniel Pohl
- Division of Gastroenterology, University Hospital of Zurich, Zurich 8006, Switzerland
| | - Peter M Keller
- Institute for Infectious Diseases, University of Bern, Bern 3010, Switzerland
| | - Valentine Bordier
- Division of Gastroenterology, University Hospital of Zurich, Zurich 8006, Switzerland
| | - Karoline Wagner
- Institute of Medical Microbiology, University of Zurich, Zurich 8006, Switzerland
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Abd albagi SO, aldayem Altayeb HN, Khalil Abuzeid NM. Molecular detection and characterization of mutation on 23S rRNA gene associated with clarithromycin resistant in Helicobacter pylori.. [DOI: 10.1101/650432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
Abstract
AbstractBackgroundHelicobacter pylori consider as pathogenic resistant bacterium was colonized mainly in stomach and causing a prolonged gastritis with gastric ulcers were progressing to gastric carcinoma. Also its resistance to antibiotic considered as the main reason for failure to eradicate of this pathogen has been difficult when this resistance occurred as mutant on protein binding site in 23s ribosomal RNA. The highest cure rates have required multidrug antimicrobial therapies including combinations of omeprazole, clarithromycin and metronidazole.ResultBacterial DNA sequence from gastritis patients with confirmed previous positive ICT samples (Stool and Bloo) were used to obtain co-related between phenotypic & genotypic variant outcome have been observed as SNPs carried on nucleotides which could be altered protein prediction as result of that caused chronic gastritis incline to gastric carcinoma due to abnormal consequence on genetic level in H. species (23s rRNA) was referred to clarithromycin resistance, was achieved on this cross-sectional studies by running two different primers were amplify in PCR machine, first one for urease producing gene (Glm as universal primer) and second one for 23s rRNA as specific primer (rp1/fp1). Two samples out of Four samples were amplified as final isolate in the first cycle and have a specific band in 23s rRNA (NO.11, NO.24) as further DNA samples investigation were sent to get our target sequence.ConclusionBioinformatics tools used to confirm a specific types of mutations give specific position responsible for bacteriostatic activity of macrolides such as clarithromycin depends on capacity to inhibit protein synthesis by binding to the 23S ribosomal subunit (23S rRNA) as resistant gene. The detection tools as MSA (multiple sequence alignment) for our nucleotides sequence to (11&24) samples with Genbank accession number 24_MK208582 and 11_MK208583. One type of mutation has been observed in nucleotide sequence (sample-24) in position 2516 (1344 _complementary) sequence result compared with reference sequence standard reference strain (H. pylori U27270) was confirmed which consider it as novel mutation in database for 23S rRNA Gene of H. pylori associated with Clarithromycin Resistance gene in Sudanese patients.
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Genetic Determinants and Prediction of Antibiotic Resistance Phenotypes in Helicobacter pylori. J Clin Med 2019; 8:jcm8010053. [PMID: 30621024 PMCID: PMC6351930 DOI: 10.3390/jcm8010053] [Citation(s) in RCA: 89] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 12/29/2018] [Accepted: 12/31/2018] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori is a major human pathogen. Diagnosis of H. pylori infection and determination of its antibiotic susceptibility still mainly rely on culture and phenotypic drug susceptibility testing (DST) that is time-consuming and laborious. Whole genome sequencing (WGS) has recently emerged in medical microbiology as a diagnostic tool for reliable drug resistance prediction in bacterial pathogens. The aim of this study was to compare phenotypic DST results with the predictions based on the presence of genetic determinants identified in the H. pylori genome using WGS. Phenotypic resistance to clarithromycin, metronidazole, tetracycline, levofloxacin, and rifampicin was determined in 140 clinical H. pylori isolates by E-Test®, and the occurrence of certain single nucleotide polymorphisms (SNPs) in target genes was determined by WGS. Overall, there was a high congruence of >99% between phenotypic DST results for clarithromycin, levofloxacin, and rifampicin and SNPs identified in the 23S rRNA, gyrA, and rpoB gene. However, it was not possible to infer a resistance phenotype for metronidazole based on the occurrence of distinct SNPs in frxA and rdxA. All 140 H. pylori isolates analysed in this study were susceptible to tetracycline, which was in accordance with the absence of double or triple nucleotide substitutions in the 16S rRNA gene.
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Abstract
PURPOSE OF REVIEW Helicobacter pylori eradication rates have fallen in recent years, mainly because of the emergence of antibiotic-resistant infections. Indeed the WHO has recently designated clarithromycin-resistant H. pylori infection a high priority for antibiotic resistance research and development. This review aims to discuss the most up-to-date information on the methods to detect H. pylori antibiotic resistance, the recent data on resistance rates, and the most appropriate treatment strategies to overcome antibiotic resistance. RECENT FINDINGS There has been active research into the development and assessment of genotypic diagnostic assays for both the invasive and noninvasive detection of antibiotic-resistant infection. There are regional variations in the prevalence of H. pylori antibiotic resistance. Primary resistance rates in general are on the rise and high rates of clarithromycin resistance (>15%) have been reported in many parts of the world. SUMMARY Optimizing antimicrobial susceptibility testing by both invasive and noninvasive means is crucial to accurately evaluate resistance rates for the optimization of both regional and personalized H. pylori treatment strategies.
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Affiliation(s)
- Sinéad M Smith
- School of Medicine, Trinity College Dublin, Dublin 2, Ireland
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Genotyping and antimicrobial resistance patterns of Helicobacter pylori in human and dogs associated with A2142G and A2143G point mutations in clarithromycin resistance. Microb Pathog 2018; 123:330-338. [PMID: 30031039 DOI: 10.1016/j.micpath.2018.07.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Revised: 07/12/2018] [Accepted: 07/13/2018] [Indexed: 02/07/2023]
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Abstract
The progress this year in Helicobacter pylori diagnosis concerned essentially endoscopy and molecular techniques. New endoscopy techniques such as blue laser imaging and magnifying narrow band imaging allow the visualization of mucosal aspects representing H. pylori infection, intestinal metaplasia, and even ambiguous early gastric cancer. Several real-time PCRs have also been used either to quantify H. pylori or to detect mutations associated with clarithromycin resistance in gastric biopsies or applied on gastric juice, stool specimens, or the oral cavity. The presence of H. pylori in free-living amebae purified from wastewater and drinking water was also determined by PCR and sequencing, as well as culture from a few wastewater samples. Among the noninvasive methods, the urea breath test was used in different conditions, including with a new test meal, which is claimed to avoid the proton-pump inhibitor washout period before testing. Several articles concerning antibody detection and stool antigen test were also published.
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Affiliation(s)
- Sabine Skrebinska
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
| | - Francis Mégraud
- Bacteriology Laboratory, Bordeaux University Hospital, French National Reference Centre for Campylobacters and Helicobacters, Bordeaux, France.,University of Bordeaux, INSERM U1053 BaRITOn, Bordeaux, France
| | - Emilie Bessède
- Bacteriology Laboratory, Bordeaux University Hospital, French National Reference Centre for Campylobacters and Helicobacters, Bordeaux, France.,University of Bordeaux, INSERM U1053 BaRITOn, Bordeaux, France
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Sun T, Chen ZX, Li P, He XL. Drug resistance of Helicobacter pylori in Zhejiang: Comparison of three methods for detection of drug resistance. Shijie Huaren Xiaohua Zazhi 2018; 26:1111-1118. [DOI: 10.11569/wcjd.v26.i18.1111] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the antibiotic resistance of Helicobacter pylori (H. pylori) in Zhejiang, and to compare the consistency of different methods for antibiotic resistance detection.
METHODS From June 2017 to September 2017, 127 H. pylori strains were isolated from gastric mucosa tissues of 305 patients who underwent gastroscopy. The sensitivity of these strains to six kinds of antibiotics was determined by the agar dilution method. The related gene mutations in 23S rRNA and gyrA were determined by quantitative real-time polymerase chain reaction (RT- PCR) and gene sequencing.
RESULTS Of the 127 H. pylori strains isolated, 124 were resistant strains and three were sensitive strains. There was no strain that was resistant to amoxicillin, tetracycline, and furazolidone. The resistance rates to clarithromycin, levofloxacin, or metronidazole were 33.86% (43/127), 44.88% (57/127), and 91.34% (116/127), respectively, and the resistance rates to the triple antibiotics was 33.86% (43/127). The main gene mutations associated with antibiotic resistance were 23S rRNA (A2143G) and gyrA (C261A/G), with mutation frequencies of 42.5% (54/127) and 15% (19/127), respectively. The drug resistance detected by RT-PCR method was consistent with that by sequencing method, but had low consistency with traditional culture method.
CONCLUSION The antibiotic resistance rates of H. pylori to clarithromycin and levofloxacin in Zhejiang Province are remarkably high. In clinical treatment, it is necessary to test antibiotic resistance to choose proper antibiotics individually to improve the eradication efficiency.
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Affiliation(s)
- Ting Sun
- Department of Pathology, Zhejiang Provincial People's Hospital, People′s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
| | - Ze-Xin Chen
- Department of Science and Education, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Peng Li
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, People′s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
| | - Xiang-Lei He
- Department of Pathology, Zhejiang Provincial People's Hospital, People′s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
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Talebi Bezmin Abadi A. Diagnosis of Helicobacter pylori Using Invasive and Noninvasive Approaches. J Pathog 2018; 2018:9064952. [PMID: 29951318 PMCID: PMC5987299 DOI: 10.1155/2018/9064952] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 04/12/2018] [Indexed: 01/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) as gram-negative and spiral microorganism is responsible for colonization in the gastric microniche for more than 50% of world population. Recent studies have shown a critical role of H. pylori in the development of peptic ulcers, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. Over the past decade, there has been a sharp interest to use noninvasive tests in diagnosis of the H. pylori infection. During the years after discovery by Marshall and Warren, it has been frequently declared that the rapid urease test (RUT) is one of the cheapest and rapid diagnostic approaches used in detecting the infection. Although the specificity and sensitivity are durable for this test, clinical experiences had shown that the ideal results are only achieved only if we take biopsies from both corpus and antrum at the same time. Given the diagnosis of the H. pylori in clinical samples, gastroenterologists are facing a long list of various molecular and nonmolecular tests. We need more in-depth researches and investigations to correctly generalize rapid and accurate molecular tests determining both bacterial identity and antibiotic resistance profile.
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Affiliation(s)
- Amin Talebi Bezmin Abadi
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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