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Elbaiomy RG, Luo X, Guo R, Deng S, Du M, El-Sappah AH, Bakeer M, Azzam MM, Elolimy AA, Madkour M, Li Z, Zhang Z. Antibiotic resistance in Helicobacter pylori: a genetic and physiological perspective. Gut Pathog 2025; 17:35. [PMID: 40410811 PMCID: PMC12102891 DOI: 10.1186/s13099-025-00704-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Accepted: 04/25/2025] [Indexed: 05/25/2025] Open
Abstract
The identification of Helicobacter pylori (H. pylori) infection as the primary etiology of gastroduodenal diseases represents a significant advancement in the field of gastroenterology. The management of these diseases has undergone a substantial transformation, and antibiotic treatment is now universally applicable. H. pylori has been the subject of numerous investigations to determine the prevalence of antibiotic resistance. However, many of these studies are limited, particularly regarding the number and representativeness of the strains assessed. Genetic and physiological modifications, such as gene mutations, efflux pump alterations, biofilm formation, and coccoid formation, contribute to the observed resistance. Our review focuses on the emergence of antibiotic-resistant strains, particularly emphasizing the various modifications of H. pylori that confer this resistance. In conclusion, we elucidate the challenges, potential solutions, and prospects in this field, providing researchers with the knowledge necessary to overcome the resistance exhibited by H. pylori.
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Affiliation(s)
- Rania G Elbaiomy
- Department of Biological Engineering, Sichuan University of Science & Engineering, Zigong, 643000, China
| | - Xiaoling Luo
- Department of Gastroenterology, FuShun People's Hospital, Zigong, 643000, China
| | - Rong Guo
- Department of Gastroenterology, FuShun People's Hospital, Zigong, 643000, China
| | - Shiyuan Deng
- Department of Biological Engineering, Sichuan University of Science & Engineering, Zigong, 643000, China
| | - Meifang Du
- Department of Biological Engineering, Sichuan University of Science & Engineering, Zigong, 643000, China
| | - Ahmed H El-Sappah
- School of Agriculture, Forestry and Food Engineering, Yibin University, Yibin, 644000, Sichuan, China
- Department of Genetics, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt
| | - Mohammed Bakeer
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FL, USA
- Division of Internal Medicine-Clinical Hematology, Al-Azhar University, Cairo, 11765, Egypt
| | - Mahmoud M Azzam
- Department of Animal Production, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Ahmed A Elolimy
- Department of Integrative Agriculture, College of Agriculture and Veterinary Medicine, United Arab Emirates University, Al Ain, Abu Dhabi, 15551, United Arab Emirates.
| | - Mahmoud Madkour
- Animal Production Department, National Research Centre, Dokki, 12622, Giza, Egypt
| | - Zaixin Li
- Department of Biological Engineering, Sichuan University of Science & Engineering, Zigong, 643000, China.
| | - Zhi Zhang
- Department of Biological Engineering, Sichuan University of Science & Engineering, Zigong, 643000, China.
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Umar Z, Tang JW, Marshall BJ, Tay ACY, Wang L. Rapid diagnosis and precision treatment of Helicobacter pylori infection in clinical settings. Crit Rev Microbiol 2025; 51:369-398. [PMID: 38910506 DOI: 10.1080/1040841x.2024.2364194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 05/08/2024] [Accepted: 05/25/2024] [Indexed: 06/25/2024]
Abstract
Helicobacter pylori is a gram-negative bacterium that colonizes the stomach of approximately half of the worldwide population, with higher prevalence in densely populated areas like Asia, the Caribbean, Latin America, and Africa. H. pylori infections range from asymptomatic cases to potentially fatal diseases, including peptic ulcers, chronic gastritis, and stomach adenocarcinoma. The management of these conditions has become more difficult due to the rising prevalence of drug-resistant H. pylori infections, which ultimately lead to gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. In 1994, the International Agency for Research on Cancer (IARC) categorized H. pylori as a Group I carcinogen, contributing to approximately 780,000 cancer cases annually. Antibiotic resistance against drugs used to treat H. pylori infections ranges between 15% and 50% worldwide, with Asian countries having exceptionally high rates. This review systematically examines the impacts of H. pylori infection, the increasing prevalence of antibiotic resistance, and the urgent need for accurate diagnosis and precision treatment. The present status of precision treatment strategies and prospective approaches for eradicating infections caused by antibiotic-resistant H. pylori will also be evaluated.
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Affiliation(s)
- Zeeshan Umar
- Marshall Laboratory of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, Guangdong Province, China
- Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China
| | - Jia-Wei Tang
- Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China
- The Marshall Centre for Infectious Diseases Research and Training, The University of Western Australia, Crawley, Western Australia, China
| | - Barry J Marshall
- Marshall Laboratory of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, Guangdong Province, China
- The Marshall Centre for Infectious Diseases Research and Training, The University of Western Australia, Crawley, Western Australia, China
- Marshall International Digestive Diseases Hospital, Zhengzhou University, Zhengzhou, Henan Province, China
- Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Alfred Chin Yen Tay
- Marshall Laboratory of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, Guangdong Province, China
- The Marshall Centre for Infectious Diseases Research and Training, The University of Western Australia, Crawley, Western Australia, China
- Marshall International Digestive Diseases Hospital, Zhengzhou University, Zhengzhou, Henan Province, China
- Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Liang Wang
- Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China
- Division of Microbiology and Immunology, School of Biomedical Sciences, The University of Western Australia, Crawley, Western Australia, China
- Center for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, China
- School of Agriculture and Food Sustainability, University of Queensland, Brisbane, Queensland, Australia
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Tourrette E, Torres RC, Svensson SL, Matsumoto T, Miftahussurur M, Fauzia KA, Alfaray RI, Vilaichone RK, Tuan VP, Wang D, Yadegar A, Olsson LM, Zhou Z, Yamaoka Y, Thorell K, Falush D. An ancient ecospecies of Helicobacter pylori. Nature 2024; 635:178-185. [PMID: 39415013 PMCID: PMC11541087 DOI: 10.1038/s41586-024-07991-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 08/23/2024] [Indexed: 10/18/2024]
Abstract
Helicobacter pylori disturbs the stomach lining during long-term colonization of its human host, with sequelae including ulcers and gastric cancer1,2. Numerous H. pylori virulence factors have been identified, showing extensive geographic variation1. Here we identify a 'Hardy' ecospecies of H. pylori that shares the ancestry of 'Ubiquitous' H. pylori from the same region in most of the genome but has nearly fixed single-nucleotide polymorphism differences in 100 genes, many of which encode outer membrane proteins and host interaction factors. Most Hardy strains have a second urease, which uses iron as a cofactor rather than nickel3, and two additional copies of the vacuolating cytotoxin VacA. Hardy strains currently have a limited distribution, including in Indigenous populations in Siberia and the Americas and in lineages that have jumped from humans to other mammals. Analysis of polymorphism data implies that Hardy and Ubiquitous coexisted in the stomachs of modern humans since before we left Africa and that both were dispersed around the world by our migrations. Our results also show that highly distinct adaptive strategies can arise and be maintained stably within bacterial populations, even in the presence of continuous genetic exchange between strains.
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Affiliation(s)
- Elise Tourrette
- Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China
| | - Roberto C Torres
- Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China
| | - Sarah L Svensson
- Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China
| | - Takashi Matsumoto
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
| | | | - Kartika Afrida Fauzia
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
- Universitas Airlangga, Surabaya, Indonesia
| | - Ricky Indra Alfaray
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
- Universitas Airlangga, Surabaya, Indonesia
| | - Ratha-Korn Vilaichone
- Gastroenterology Unit, Department of Medicine and Center of Excellence in Digestive Diseases, Thammasat University, Bangkok, Thailand
| | - Vo Phuoc Tuan
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
- Cho Ray Hospital, Ho Chi Minh City, Vietnam
| | - Difei Wang
- Cancer Genomics Research Lab, Frederick National Lab for Cancer Research, Rockville, MD, USA
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Lisa M Olsson
- The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Zhemin Zhou
- Pasteurien College, Suzhou Medical College, Soochow University, Suzhou, China
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan.
- Universitas Airlangga, Surabaya, Indonesia.
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX, USA.
- Research center for global and local infectious diseases, Oita University, Yufu, Japan.
| | - Kaisa Thorell
- Department of Chemistry and Molecular Biology, Faculty of Science, University of Gothenburg, Gothenburg, Sweden.
| | - Daniel Falush
- Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China.
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Elsabaawy M, Shaban A, Al-Arab AE, Elbahr O, Edrees A, Afify S. Vonoprazan a novel potassium competitive acid blocker; another leap forward. PRZEGLAD GASTROENTEROLOGICZNY 2024; 19:135-142. [PMID: 38939071 PMCID: PMC11200074 DOI: 10.5114/pg.2024.139426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Accepted: 02/10/2023] [Indexed: 06/29/2024]
Abstract
INTRODUCTION The eradication rate of Helicobacter pylori (H. pylori) has decreased due to antibiotics resistance and inadequate acid suppression. Vonoprazan is a novel potassium-competitive acid blocker (P-CAB), which has a rapid and sustained acid inhibitory effect and may be more effective than conventional proton pump inhibitors (PPIs) in H. pylori eradication. AIM to study the efficacy and safety of vonoprazan as a component of first-line H. pylori eradication treatment compared with conventional PPI-based therapy. MATERIAL AND METHODS This randomised (one to one) non-blinded study was conducted on 400 consecutive proven H. pylori infected patients, of whom 200 received vonoprazan-based triple therapy, while 200 patients received PPI-based triple therapy for 14 days. The study outcomes were evaluated as eradication rate and adverse events in both patient groups. RESULTS The eradication rate was 86% in the vonoprazan group and 74.5% in the PPI group. The vonoprazan eradication rate was significantly higher than that of PPIs (p = 0.004). There was no significant difference regarding adverse events between both patient groups. CONCLUSIONS Vonoprazan-based therapy was more effective than PPI-based therapy as a first-line H. pylori eradication treatment. Vonoprazan was generally safe and well tolerated.
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Affiliation(s)
- Maha Elsabaawy
- Depatment of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koum, Menoufia, Egypt
| | - Ahmed Shaban
- Depatment of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koum, Menoufia, Egypt
| | - Ahmed Ezz Al-Arab
- Depatment of internal Medicine, Faculty of Medicine, Menoufia University, Shebeen El-Koum, Menoufia, Egypt
| | - Osama Elbahr
- Depatment of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koum, Menoufia, Egypt
| | - Ahmed Edrees
- Depatment of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koum, Menoufia, Egypt
| | - Sameh Afify
- Depatment of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koum, Menoufia, Egypt
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Arfi S, Sharma P, Kumar M, Mehra S, Das K, Das R, Setya A. Antibiotic susceptibility pattern of Helicobacter pylori against eight antibiotics: A study from North India. Helicobacter 2024; 29:e13093. [PMID: 38757432 DOI: 10.1111/hel.13093] [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: 03/04/2024] [Revised: 05/03/2024] [Accepted: 05/06/2024] [Indexed: 05/18/2024]
Abstract
BACKGROUND The purpose of this analysis is to evaluate the antimicrobial susceptibility of eight drugs effective against Helicobacter pylori (H. pylori) strains and the genetic diversity of H. pylori virulence genes to foresee clinical outcomes in North India. MATERIALS AND METHODS Fifty-eight H. pylori strains isolated from patients suffering from various gastrointestinal (GI) diseases were included in the study. MICs of various antibiotics were determined by the agar dilution method. The chi-squared test and Fisher exact test were used to determine the p-value, which was considered significant at p-value ≤ 0.05. RStudio 4.0 was used to for the data visualization. RESULTS The prevalence of drug resistance was found to be: cefixime (CFM) (41.3%), furazolidone (FZD) (34.4%), amoxicillin (AMX) (20.7%), levofloxacin (LVFX) (70.7%), metronidazole (MTZ) (39.6%), tetracycline (TET) (20.7%), clarithromycin (CLA) (17.2%), and rifabutin (RIF) (17.2%). Out of 58 H. pylori strains, 3 were pan susceptible. There were H. pylori strains with single-drug resistance (21.8%, 12/55), dual resistance (30.9%, 17/55), triple resistance (20%, 11/55), and multidrug resistance (27.3%, 15/55). The resistance rate in MTZ, CLA and RIF were found to be significantly higher in females as compared to males (p = 0.005, p = 0.002, and p = 0.02), respectively. The resistance to TET exhibited significantly higher levels in gastritis compared to GERD, DU, and other disease groups (p = 0.04) respectively. CONCLUSION TET, AMX, CLA, and RIF were found to be more effective antibiotics against H. pylori infections, whereas more studies are required to provide evidence on increasing resistance rate of LVFX.
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Affiliation(s)
- Safiya Arfi
- Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
| | - Prateek Sharma
- Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
| | - Mithun Kumar
- Department of Gastroenterology and Hepatology, Max Super Speciality Hospital, Saket, New Delhi, India
| | - Shubham Mehra
- Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
| | - Kunal Das
- Department of Gastroenterology, Yashoda Super Specialty Hospital, Ghaziabad, Uttar Pradesh, India
| | - Rajashree Das
- Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
| | - Ashwini Setya
- Department of Gastroenterology and Hepatology, Max Super Speciality Hospital, Saket, New Delhi, India
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Alhalabi M, Almokdad R. Efficacy of a 2-week therapy with levofloxacin concomitant versus a levofloxacin sequential regimen for Helicobacter pylori infection in the Syrian population: a study protocol for randomized controlled trial. Trials 2024; 25:55. [PMID: 38225650 PMCID: PMC10789050 DOI: 10.1186/s13063-024-07906-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Accepted: 01/02/2024] [Indexed: 01/17/2024] Open
Abstract
BACKGROUND Treating Helicobacter pylori is becoming increasingly difficult with the development of bacterial resistance to many established treatment regimens. As a result, researchers are constantly looking for novel and effective treatments. This trial aims to establish the efficacy of levofloxacin-based sequential treatment regimen and concomitant levofloxacin-based regimen as empirical first-line therapy in the Syrian population. METHOD This is an open-label, prospective, single-center, parallel, active-controlled, superiority, randomized clinical trial. The recruitment will target Helicobacter pylori-positive males and females between the ages of 18 and 65 to evaluate the efficacy of empirical first-line therapy in the Syrian population. We are planning to recruit up to 300 patients which is twice the required sample size. One hundred fifty individuals will be randomly assigned to undergo either a sequential levofloxacin-based treatment regimen or a concomitant levofloxacin-based regimen. High-dose dual therapy (proton-pump inhibitor and amoxicillin) will be the rescue therapy in the event of first-line failure. The first-line eradication rate in both groups is the primary outcome, and one of the secondary outcomes is the overall eradication rate of high-dose dual therapy in the event of first-line treatment protocol failure. Intention-to-treat analysis and per-protocol analysis will be used to evaluate the eradication rates of Helicobacter pylori for first-line treatment protocols. DISCUSSION For the first time in the Syrian population, this randomized controlled trial will provide objective and accurate evidence about the efficacy of a sequential levofloxacin-based treatment regimen. TRIAL REGISTRATION ClinicalTrials.gov NCT06065267 . Registered on October 3, 2023. Prospective registered. Enrollment of the first participant has not started yet.
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Affiliation(s)
- Marouf Alhalabi
- Gastroenterology Department, Damascus Hospital, Almujtahed Street, Damascus, Syria.
| | - Rasha Almokdad
- Gastroenterology Department, Damascus Hospital, Almujtahed Street, Damascus, Syria
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Dutta S, Jain S, Das K, Verma P, Som A, Das R. Primary antibiotic resistance of Helicobacter pylori in India over the past two decades: A systematic review. Helicobacter 2024; 29:e13057. [PMID: 38415810 DOI: 10.1111/hel.13057] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Revised: 12/19/2023] [Accepted: 02/06/2024] [Indexed: 02/29/2024]
Abstract
BACKGROUND Helicobacter pylori antibiotic resistance has undergone vast changes in the last two decades. No systematic review has been done on the prevalence of antibiotic resistant H. pylori in India in the last two decades. We evaluated the pattern of resistance rates across various regions of India. MATERIALS AND METHODS A systematic review of the geographical variations in antibiotic resistance pattern of H. pylori was conducted using PubMed, Google Scholar, Web of Science, Science Direct, etc. for articles published between January 1, 2000 and May 30, 2023. Random effects-model-based Cochran's Q test, I2 statistics, and chi-squared tests were used to measure heterogeneity. RESULTS The overall resistance was highest against metronidazole (77.65%) followed by amoxicillin (37.78%), levofloxacin (32.8%), clarithromycin (35.64%), furazolidone (12.03%), and tetracycline (11.63%). 14.7% of the H. pylori isolates were multi-drug resistant. Under meta-analysis of each antibiotic, high heterogeneity levels were observed having I2 ranges from 86.53% to 97.70% at p < 0.0001. In sub-group analysis, Metronidazole has a stable rate of resistance as compared to other antibiotics. Other antibiotics have had a downtrend in the last 5 years except for levofloxacin, which has had an uptrend in the resistance rate for the past 5 years. Hence, one should avoid using metronidazole for any kind of first-line treatment. CONCLUSIONS Metronidazole resistance is high in most regions of India except Assam and Mumbai while clarithromycin is found to be ineffective in South India, Gujarat, and Kashmir. As compared to other antibiotics, resistance to amoxicillin is generally low except in certain regions (Hyderabad, Chennai, and the Gangetic belt of North India). Tetracycline and Furazolidone have the least resistance rates and should be part of anti- H. pylori regimens. The resurgence of high single and multidrug resistance to the commonly used drugs suggests the need for newer antibiotics and regular resistance surveillance studies.
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Affiliation(s)
- Spriha Dutta
- Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
| | - Surbhi Jain
- Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
| | - Kunal Das
- Department of Gastroenterology, Yashoda Superspeciality Hospital, Kausambi, Ghaziabad, Uttar Pradesh, India
| | - Prashant Verma
- Department of Statistics, University of Allahabad, Prayagraj, Uttar Pradesh, India
| | - Anup Som
- Centre of Bioinformatics, Institute of Interdisciplinary Studies, University of Allahabad, Prayagraj, Uttar Pradesh, India
| | - Rajashree Das
- Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
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Jacob TV, Doshi GM. A Mini-review on Helicobacter pylori with Gastric Cancer and Available Treatments. Endocr Metab Immune Disord Drug Targets 2024; 24:277-290. [PMID: 37622707 DOI: 10.2174/1871530323666230824161901] [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: 05/30/2023] [Revised: 07/22/2023] [Accepted: 07/26/2023] [Indexed: 08/26/2023]
Abstract
Helicobacter pylori (H. pylori) is the most thoroughly researched etiological component for stomach inflammation and malignancies. Even though there are conventional recommendations and treatment regimens for eradicating H. pylori, failure rates continue to climb. Antibiotic resistance contributes significantly to misdiagnoses, false positive results, and clinical failures, all of which raise the chance of infection recurrence. This review aims to explore the molecular mechanisms underlying drug resistance in H. pylori and discuss novel approaches for detecting genotypic resistance. Modulation of drug uptake/ efflux, biofilm, and coccoid development. Newer genome sequencing approaches capable of detecting H. pylori genotypic resistance are presented. Prolonged infection in the stomach causes major problems such as gastric cancer. The review discusses how H. pylori causes stomach cancer, recent biomarkers such as miRNAs, molecular pathways in the development of gastric cancer, and diagnostic methods and clinical trials for the disease. Efforts have been made to summarize the recent advancements made toward early diagnosis and novel therapeutic approaches for H. pylori-induced gastric cancer.
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Affiliation(s)
- Teresa V Jacob
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V.M. Road, Vile Parle (W), Mumbai, 400056, India
| | - Gaurav M Doshi
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V.M. Road, Vile Parle (W), Mumbai, 400056, India
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Borody TJ, Ng J, Dolai S. Unlocking the path to efficient H. pylori eradication: Embracing potassium-competitive acid blockers (P-CABs). Saudi J Gastroenterol 2023; 29:323-325. [PMID: 37706422 PMCID: PMC10754378 DOI: 10.4103/sjg.sjg_297_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/15/2023] Open
Affiliation(s)
- Thomas J. Borody
- Department of Gastroenterology, The Centre for Digestive Diseases (CDD), Sydney, NSW, Australia
| | - John Ng
- Axent Medical Pty Ltd., Sydney, NSW, Australia
| | - Sibasish Dolai
- Department of Gastroenterology, The Centre for Digestive Diseases (CDD), Sydney, NSW, Australia
- Axent Medical Pty Ltd., Sydney, NSW, Australia
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10
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Fatima A, Ibrahim M, Naseer A, Pervez A, Asad M, Shah AA, Hasan F, Alonazi WB, Ferheen I, Khan S. Identification, Genome Sequencing, and Characterizations of Helicobacter pylori Sourced from Pakistan. Microorganisms 2023; 11:2658. [PMID: 38004670 PMCID: PMC10673187 DOI: 10.3390/microorganisms11112658] [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: 09/24/2023] [Revised: 10/19/2023] [Accepted: 10/28/2023] [Indexed: 11/26/2023] Open
Abstract
The stomach's colonization by Helicobacter pylori (H. pylori) results in gastritis, ulcers, and stomach cancer. Frequently, pain is treated with medication, but resistant H. pylori infections are not. Therefore, it is important to find pharmacological targets and improved treatments for resistant H. pylori strains. The aim of the current study was sampling, identification, drug susceptibility testing following genome sequencing and comparative genome-wide analysis of selected H. pylori strains from Pakistan with three representative strains for virulence and drug-resistant characteristics. Based on culture, biochemistry, and molecular biology, 84 strains of H. pylori were identified, which made up 47% of the enrolled cases. Among all H. pylori strains, the highest resistance was reported for metronidazole with 82 H. pylori strains (98%), followed by clarithromycin with 62 resistant strains (74%). Among metronidazole-resistant strains, 38 strains (46%) were also resistant to clarithromycin, contributing 61% of clarithromycin resistant cases. Two strains, HPA1 and HPA2, isolated from 'gastritis' and 'gastric ulcer' patients, respectively, were further processed for WGS. The draft genome sequences of H. pylori strains HPA1 and HPA2 encode 1.66 Mbp and 1.67 Mbp genome size, 24 and 4 contiguous DNA sequences, and 1650 and 1625 coding sequences, respectively. Both the genomes showed greater than 90% similarity with the reference strain H. pylori ATCC 43504/PMSS1. The antibiotic-resistant genes were identified among all the strains with overall similarity above 95%, with minor differences in the sequence similarity. Using the virulent gene data obtained from the Virulence Factor Database, 75 to 85 virulent genes were identified in the five genome assemblies with various key genes such as cytolethal distending toxin (cdt), type IV secretion system, cag PAI, plasticity region, cell-motility- and flagellar-associated genes, neutrophil-activating protein (HP-NAP), T4SS effector cytotoxin-associated gene A (cagA), and urease-associated genes ureA and ureB, etc. Sequence similarity between the virulence factors found in this study and reference genes was at least 90%. In summary, the results of our study showed the relationship between clinical results and specific H. pylori strains' (HPA1 and HPA2) genetics such as antibiotic resistance and specific virulence factors. These findings provide valued understanding of the epidemiology of H. pylori-associated diseases. Moreover, identification and genomics analysis have provided insights into the epidemiology, genetic diversity, pathogenicity, and potential drug resistance genes of H. pylori strains, offering a foundation for developing more targeted and effective medical interventions, including anti-virulent medications.
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Affiliation(s)
- Anees Fatima
- Department of Microbiology, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad 45320, Pakistan; (A.F.); (A.A.S.); (F.H.)
- Department of Microbiology, Faculty of Health & Biological Sciences, Abbottabad University of Science & Technology, Abbottabad 22500, Pakistan
| | - Muhammad Ibrahim
- Department of Biosciences, COMSATS University Islamabad (CUI), Sahiwal Campus, Sahiwal 55000, Pakistan (M.A.)
| | - Adil Naseer
- Department of Gastroenterology, Ayub Medical College, Main Mansehra Road, Abbottabad 22020, Pakistan;
| | - Arshid Pervez
- Department of Environmental Sciences, COMSATS University Islamabad (CUI), Abbottabad Campus, University Road, Tobe Camp, Abbottabad 22010, Pakistan;
| | - Muhammad Asad
- Department of Biosciences, COMSATS University Islamabad (CUI), Sahiwal Campus, Sahiwal 55000, Pakistan (M.A.)
| | - Aamer Ali Shah
- Department of Microbiology, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad 45320, Pakistan; (A.F.); (A.A.S.); (F.H.)
| | - Fariha Hasan
- Department of Microbiology, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad 45320, Pakistan; (A.F.); (A.A.S.); (F.H.)
| | - Wadi B. Alonazi
- Health Administration Department, College of Business Administration, King Saud University, Riyadh 11587, Saudi Arabia;
| | - Ifra Ferheen
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy;
| | - Samiullah Khan
- Department of Microbiology, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad 45320, Pakistan; (A.F.); (A.A.S.); (F.H.)
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11
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Rajendran V, Ponnuraj K. High-throughput virtual screening and molecular dynamics simulation reveals NPC170742 a novel chalconoid compound as a potential inhibitor of D-glycero-D-manno-heptose-1,7-bisphosphate 7-phosphatase in Helicobacter pylori. J Biomol Struct Dyn 2023; 42:10911-10921. [PMID: 37723879 DOI: 10.1080/07391102.2023.2259483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 08/23/2023] [Indexed: 09/20/2023]
Abstract
Helicobacter pylori is a gram negative spiral shaped bacteria that causes peptic ulcer and gastric cancer. It Is the sixth most prevalent cancer in the world and the third leading cause of cancer death. The increase in reported cases of H. pylori resistance to the drugs and antibiotics shows the need for the development of new and efficient drugs against the pathogen. In the present study, D-glycero-D-manno-heptose-1,7-bisphosphate 7-phosphatase (GmhB), an enzyme involved in the biosynthesis of lipopolysaccharides that encourages bacterial adherence, self-aggregation and identifying the host cells was modelled and the active sites were predicted through POCASA which is an automated ligand binding site prediction server. Natural product activity and species source (NPASS) is a database of 96,481 natural compounds that were subjected to virtual screening workflow that includes Qikprop, Lipinski rule, filtering out reactive functional groups followed by high throughput virtual screening and the top 10 compounds were selected for further induced fit docking along with the substrate D-glycero-β-D-manno-heptose 1,7-bisphosphate. The compound NPC170742 (Alpha, Beta, 3,4,5,2',4',6'-Octahydroxy dihydrochalcone) showed higher affinity than the substrate, and both the substrate D-glycero-β-D-manno-heptose 1,7-bisphosphate and the compound NPC170742 were subjected to molecular dynamics simulation. The results exposed the compound NPC170742 could be a potential lead compound against the enzyme D-glycero-D-manno-heptose-1,7-bisphosphate 7-phosphatase of H. pylori.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Vijayakumar Rajendran
- Centre for Advanced Studies in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai, India
| | - Karthe Ponnuraj
- Centre for Advanced Studies in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai, India
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12
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Chouhan D, Retnakumar RJ, Devi TB, Dharmaseelan S, Alexander SM, Devadas K, Chattopadhyay S, Nair GB, Pillai MR. Unusually high clarithromycin resistance in Mycobacterium abscessus subsp. abscessus isolated from human gastric epithelium. Front Microbiol 2023; 14:1193380. [PMID: 37700866 PMCID: PMC10494244 DOI: 10.3389/fmicb.2023.1193380] [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: 03/24/2023] [Accepted: 08/07/2023] [Indexed: 09/14/2023] Open
Abstract
Mycobacterium abscessus subsp. abscessus is a rapidly growing facultative intracellular pathogen that usually infects human lung and skin epithelium. Recently, we and another group have shown that it also has the potential to colonize human gastric epithelium, but its significance with respect to gastric diseases remains unclear. Although Helicobacter pylori still remains the only definite gastric pathogen, recent studies have shown that M. abscessus subsp. abscessus also has the potential to colonize human gastric epithelium. M. abscessus subsp. abscessus is known to exhibit multidrug resistance and clarithromycin has been used as the drug of choice. We aimed to determine the clarithromycin resistance profile of 117 (74 rough and 43 smooth) gastric M. abscessus subsp. abscessus strains and to detect the point mutations in rrl and erm (41) genes conferring the resistance. Our data showed 79.48% (19 smooth and 74 rough) of M. abscessus subsp. abscessus strains were resistant to clarithromycin (MIC90 ≤ 512 μg/mL), while 20.51% (24 smooth) were susceptible (MIC90 ≤ 8 μg/mL). Nucleotide sequence analysis of the rrl gene with reference strains of M. abscessus subsp. abscessus did not show any mutation that is relevant to the clarithromycin resistance. However, analysis of erm (41) gene showed that M. abscessus subsp. abscessus strains, which were susceptible to clarithromycin had C, C, G, and C at their nucleotide positions 28, 159, 238, and 330, respectively, while the resistant strains showed T, T, A, and A at the same positions. Based on antibiogram and sequence analysis data we recommend further studies involving genomic analysis to identify the other genes involved in high clarithromycin resistance in gastric M. abscessus subsp. abscessus along with the mechanisms involved.
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Affiliation(s)
- Deepak Chouhan
- Pathogen Biology Group, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
- PhD Program in Biotechnology, Manipal Academy of Higher Education (MAHE), Manipal, India
| | - R. J. Retnakumar
- Pathogen Biology Group, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
- PhD Program in Biotechnology, Manipal Academy of Higher Education (MAHE), Manipal, India
| | - T. Barani Devi
- Pathogen Biology Group, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
| | - Sanjai Dharmaseelan
- Pathogen Biology Group, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
| | - Sneha Mary Alexander
- Pathogen Biology Group, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
| | - Krishnadas Devadas
- Department of Gastroenterology, Government Medical College, Thiruvananthapuram, India
| | - Santanu Chattopadhyay
- Pathogen Biology Group, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
| | - Gopinath Balakrish Nair
- Pathogen Biology Group, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
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13
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Dutta AK. Choosing optimum regimen for treating Helicobacter pylori infection: Regional data may be the quintessential guide. Indian J Gastroenterol 2023; 42:448-451. [PMID: 37466880 DOI: 10.1007/s12664-023-01425-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/20/2023]
Affiliation(s)
- Amit Kumar Dutta
- Department of Gastroenterology, Christian Medical College, Vellore, 632 004, India.
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14
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Rokkas T, Ekmektzoglou K. Advances in the pharmacological and regulatory management of multidrug resistant Helicobacter pylori. Expert Rev Clin Pharmacol 2023; 16:1229-1237. [PMID: 37937850 DOI: 10.1080/17512433.2023.2282061] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 11/07/2023] [Indexed: 11/09/2023]
Abstract
INTRODUCTION Antibiotic resistance of Helicobacter pylori (H. pylori) hampers the success of eradication and in recent years multidrug resistance (MDR) shows an increase worldwide. AREAS COVERED This review covers current aspects of pharmacological and regulatory management of MDR-resistant H. pylori infection. EXPERT OPINION MDR H. pylori is increasing worldwide and its prevalence varies both between continents and countries. High consumption and misuse of antibiotics, H. pylori treatment failures and bacterial factors such as mutations, efflux pumps and biofilms are among the factors associated with MDR. Important steps for confronting the rise of MDR H. pylori strains should follow the principles of antibiotic stewardship, i.e. eradication regimens should be optimized with regard to all aspects of therapy, including drugs, doses, formulation, frequency of administration, administration in relation to meals and duration of therapy that reliably achieve at least 90% (preferably >95%) cure rates in adherent patients with susceptible infections.
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Affiliation(s)
- Theodore Rokkas
- Gastroenterology Clinic, Henry Dunant Hospital, Athens, Greece
- Medical School, European University of Cyprus, Nicosia, Cyprus
| | - Konstantinos Ekmektzoglou
- Gastroenterology Clinic, Henry Dunant Hospital, Athens, Greece
- Medical School, European University of Cyprus, Nicosia, Cyprus
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15
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Sholeh M, Khoshnood S, Azimi T, Mohamadi J, Kaviar VH, Hashemian M, Karamollahi S, Sadeghifard N, Heidarizadeh H, Heidary M, Saki M. The prevalence of clarithromycin-resistant Helicobacter pylori isolates: a systematic review and meta-analysis. PeerJ 2023; 11:e15121. [PMID: 37016679 PMCID: PMC10066884 DOI: 10.7717/peerj.15121] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 03/03/2023] [Indexed: 04/06/2023] Open
Abstract
BACKGROUND Knowledge of global clarithromycin (CLA)-resistant rates of Helicobacter pylori (H. pylori) is crucial for decision of the most appropriate eradication therapies with good clinical outcomes. Therefore, this review and meta-analysis aimed to evaluate the global prevalence of the CLA resistance in H. pylori to provide some guidance for selecting the first-line antibiotics. METHOD A comprehensive search was performed for relevant literature until April 2021 in PubMed, Embase, and Web of Science databases. Freeman-Tukey double arcsine transformation was performed to estimate the weighted pooled prevalence of resistance. RESULTS The meta-analysis included 248 articles. The prevalence of CLA-resistant H. pylori was 27.53% (95% CI [25.41-29.69]). The heterogeneity between reports was significant (I2 = 97.80%, P < 0.01). The resistance rate increased from 24.28% in 2010-2017 to 32.14% in 2018-2021 (P < 0.01). Iran, with 38 articles, has the most report. Nevertheless, Switzerland, Portugal, and Israel had the highest resistance rates (67.16%, 48.11%, and 46.12%, respectively). The heterogeneity between the continents and the antimicrobial susceptibility methods also interpreted standard guidelines and breakpoints was insignificant (P > 0.05). CONCLUSION Overall CLA resistance rate was 27.53%, worldwide. The difference in CLA resistance rate among the included studies can be due to several reasons such as differences in antibiotic prescription rates in various geographic areas, use of different breakpoints or inaccurate criteria in performed studies, and the emergence of multidrug-resistant (MDR) strains.
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Affiliation(s)
- Mohammad Sholeh
- Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran
| | - Saeed Khoshnood
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
- Student Research Committee, Ilam University of Medical Sciences, Ilam, Iran
| | - Taher Azimi
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Jasem Mohamadi
- Department of Pediatrics, School of Medicine, Emam Khomeini Hospital, Ilam University of Medical Sciences, Ilam, Iran
| | - Vahab Hassan Kaviar
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Marzieh Hashemian
- Department of Microbiology, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Somayeh Karamollahi
- Department of Microbiology, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Nourkhoda Sadeghifard
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Hedayat Heidarizadeh
- Department of Pediatrics, School of Medicine, Emam Khomeini Hospital, Ilam University of Medical Sciences, Ilam, Iran
| | - Mohsen Heidary
- Department of Laboratory Sciences, School of Paramedical Sciences, Sabzevar University of Medical Sciences, Sabzevar, Iran
- Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Morteza Saki
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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16
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Shrestha AB, Pokharel P, Sapkota UH, Shrestha S, Mohamed SA, Khanal S, Jha SK, Mohanty A, Padhi BK, Asija A, Sedhai YR, Rijal R, Singh K, Chattu VK, Rodriguez-Morales AJ, Barboza JJ, Sah R. Drug Resistance Patterns of Commonly Used Antibiotics for the Treatment of Helicobacter pylori Infection among South Asian Countries: A Systematic Review and Meta-Analysis. Trop Med Infect Dis 2023; 8:tropicalmed8030172. [PMID: 36977173 PMCID: PMC10051479 DOI: 10.3390/tropicalmed8030172] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/17/2023] [Accepted: 02/24/2023] [Indexed: 03/18/2023] Open
Abstract
Background: In South Asia, resistance to commonly used antibiotics for the treatment of Helicobacter pylori infection is increasing. Despite this, accurate estimates of overall antibiotic resistance are missing. Thus, this review aims to analyze the resistance rates of commonly used antibiotics for the treatment of H. pylori in South Asia. Methods: The systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. We searched five medical databases for relevant studies from inception to September 2022. A random effect model with a 95% confidence interval (CI) was used to calculate the pooled prevalence of antibiotic resistance. Results: This systematic review and meta-analysis included 23 articles, 6357 patients, 3294 Helicobacter pylori isolates, and 2192 samples for antibiotic resistance. The prevalences of antibiotic resistance to common antibiotics were clarithromycin: 27% (95%CI: 0.17–0.38), metronidazole: 69% (95%CI: 0.62–0.76), tetracycline: 16% (95%CI: 0.06–0.25), amoxicillin: 23% (95%CI: 0.15–0.30), ciprofloxacin: 12% (95%CI: 0.04–0.23), levofloxacin: 34% (95%CI: 0.22–0.47), and furazolidone: 14% (95%CI: 0.06–0.22). Subgroup analysis showed antibiotic resistances were more prevalent in Pakistan, India, and Bangladesh. Furthermore, a ten-year trend analysis showed the increasing resistance prevalence for clarithromycin (21% to 30%), ciprofloxacin (3% to 16%), and tetracycline (5% to 20%) from 2003 to 2022. Conclusion: This meta-analysis showed a high prevalence of resistance among the commonly used antibiotics for H. pylori in South Asian countries. Furthermore, antibiotic resistance has been increasing over the time of 20 years. In order to tackle this situation, a robust surveillance system, and strict adherence to antibiotic stewardship are required.
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Affiliation(s)
| | - Pashupati Pokharel
- Department of Medicine, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu 1524, Nepal
| | | | - Sajina Shrestha
- Department of Internal Medicine, KIST Medical College, Imadol, Patan 284128, Nepal
| | - Shueb A. Mohamed
- School of Medicine, Alexandria University, Alexandria 21568, Egypt
| | - Surakshya Khanal
- Department of Medicine, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu 1524, Nepal
| | - Saroj Kumar Jha
- Department of Medicine, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu 1524, Nepal
| | - Aroop Mohanty
- Department of Microbiology, All India Institute of Medical Sciences, Gorakhpur 273008, India
| | - Bijaya Kumar Padhi
- Department of Community Medicine and School of Public Health, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Ankush Asija
- School of Medicine, West Virginia University, Morgantown, WV 26506, USA
| | - Yub Raj Sedhai
- Division of Pulmonary Disease and Critical Care Medicine, University of Kentucky College of Medicine, Bowling Green, KY 42101, USA
| | - Rishikesh Rijal
- Division of infectious Diseases, University of Louisville, Louisville, KY 40208, USA
| | - Karan Singh
- Division of Pulmonary Disease and Critical Care Medicine, University of Kentucky College of Medicine, Bowling Green, KY 42101, USA
| | - Vijay Kumar Chattu
- Department of Occupational Science and Occupational Therapy, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5R 0A3, Canada
- Center for Transdisciplinary Research, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600077, India
- Department of Community Medicine, Faculty of Medicine, Datta Meghe Institute of Medical Sciences, Wardha 442107, India
| | - Alfonso J. Rodriguez-Morales
- Grupo de Investigación Biomedicina, Faculty of Medicine, Fundación Universitaria Autónoma de las Américas, Pereira 660003, Colombia
- Master’s Program in Clinical Epidemiology and Biostatistics, Universidad Cientifica del Sur, Lima 15846, Peru
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut 1101, Lebanon
| | - Joshuan J. Barboza
- Escuela de Medicina, Universidad Cesar Vallejo, Trujillo 13007, Peru
- Correspondence: (J.J.B.); (R.S.)
| | - Ranjit Sah
- Department of Medicine, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu 1524, Nepal
- Department of Microbiology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune 411018, India
- Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth, Pune 411018, India
- Correspondence: (J.J.B.); (R.S.)
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17
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Srisuphanunt M, Wilairatana P, Kooltheat N, Duangchan T, Katzenmeier G, Rose JB. Molecular Mechanisms of Antibiotic Resistance and Novel Treatment Strategies for Helicobacter pylori Infections. Trop Med Infect Dis 2023; 8:163. [PMID: 36977164 PMCID: PMC10057134 DOI: 10.3390/tropicalmed8030163] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 03/06/2023] [Accepted: 03/06/2023] [Indexed: 03/18/2023] Open
Abstract
Helicobacter pylori infects approximately 50% of the world's population and is considered the major etiological agent of severe gastric diseases, such as peptic ulcers and gastric carcinoma. Increasing resistance to standard antibiotics has now led to an ever-decreasing efficacy of eradication therapies and the development of novel and improved regimens for treatment is urgently required. Substantial progress has been made over the past few years in the identification of molecular mechanisms which are conducive to resistant phenotypes as well as for efficient strategies to counteract strain resistance and to avoid the use of ineffective antibiotics. These involve molecular testing methods, improved salvage therapies, and the discovery of novel and potent antimicrobial compounds. High rates of prevalence and gastric cancer are currently observed in Asian countries, including Japan, China, Korea, and Taiwan, where concomitantly intensive research efforts were initiated to explore advanced eradication regimens aimed at reducing the risk of gastric cancer. In this review, we present an overview of the known molecular mechanisms of antibiotic resistance and discuss recent intervention strategies for H. pylori diseases, with a view of the research progress in Asian countries.
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Affiliation(s)
- Mayuna Srisuphanunt
- Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand
- Excellent Center for Dengue and Community Public Health, School of Public Health, Walailak University, Nakhon Si Thammarat 80160, Thailand
| | - Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | - Nateelak Kooltheat
- Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand
- Hematology and Transfusion Science Research Center, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand
| | - Thitinat Duangchan
- Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand
- Hematology and Transfusion Science Research Center, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand
| | - Gerd Katzenmeier
- Akkhraratchakumari Veterinary College, Walailak University, Nakhon Si Thammarat 80160, Thailand
| | - Joan B. Rose
- Department of Fisheries and Wildlife, Michigan State University, East Lansing, MI 48823, USA
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18
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Jafar M, Sajjad Ahmad Khan M, Salahuddin M, Zahoor S, Mohammed Hesham Slais H, Ibrahim Alalwan L, Radhi Alshaban H. DEVELOPMENT OF APIGENIN LOADED GASTRORETENTIVE MICROSPONGE FOR THE TARGETING OF HELICO BACTER PYLORI. Saudi Pharm J 2023; 31:659-668. [PMID: 37181149 PMCID: PMC10172626 DOI: 10.1016/j.jsps.2023.03.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 03/07/2023] [Indexed: 03/18/2023] Open
Abstract
The goal of the present work was to invent an apigenin-stacked gastroretentive microsponge to target H. pylori. The quasi-emulsion technique was used to prepare microsponges, which were then tested for various physicochemical properties, in-vivo gastric retention, and in-vitro anti-H. pylori study. The microsponge that demonstrated a comparatively good product yield (76.23 ± 0.84), excellent entrapment efficiency (97.84 ± 0.85), sustained in-vitro gastric retention period, and prolonged drug release were chosen for further investigations. The microsponge's SEM analysis showed that it had a spherical form, porous surface, and interconnected spaces. No drug-polymer interactions were detected in the FTIR investigation. Apigenin was found to be dispersed in the microsponge's polymeric matrix according to DSC & XRD investigations. Moreover, the microsponge in the rat's stomach floated for 4 h, according to the ultrasonography. The antibacterial activity of apigenin against H. pylori was nearly two folds more than the pure apigenin and had a more sustained release in the best microsponge, according to the in vitro MIC data, when compared to pure apigenin. To sum up, the developed gastroretentive microsponge with apigenin offers a viable alternative for the efficient targeting of H. pylori. But more preclinical & clinical studies of our best microsponge would yield considerably more fruitful results.
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19
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Dascălu RI, Bolocan A, Păduaru DN, Constantinescu A, Mitache MM, Stoica AD, Andronic O. Multidrug resistance in Helicobacter pylori infection. Front Microbiol 2023; 14:1128497. [PMID: 36922977 PMCID: PMC10009102 DOI: 10.3389/fmicb.2023.1128497] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 01/30/2023] [Indexed: 03/02/2023] Open
Abstract
Helicobacter pylori (Hp), a well-known human pathogen, causes one of the most common chronic bacterial infections and plays an important role in the emergence of chronic progressive gastric inflammation and a variety of gastrointestinal diseases. The prevalence of Hp infection varies worldwide and is indirectly proportional to socio-economic status, especially during childhood. The response to the eradication therapy significantly depends on the antibiotic resistance specific to each geographical region; thus, currently, given the increasing prevalence of antimicrobial resistance (especially to clarithromycin, metronidazole, and levofloxacin), successful treatment for Hp eradication has become a real challenge and a critical issue. The most incriminated factors associated with multidrug resistance (MDR) in Hp proved to be the overuse or the improper use of antibiotics, poor medication adherence, and bacterial-related factors including efflux pumps, mutations, and biofilms. Up to 30% of first-line therapy fails due to poor patient compliance, high gastric acidity, or high bacteremia levels. Hence, it is of great importance to consider new eradication regimens such as vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, requiring further studies and thorough assessment. Strain susceptibility testing is also necessary for an optimal approach.
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Affiliation(s)
| | - Alexandra Bolocan
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.,University Emergency Hospital of Bucharest, Bucharest, Romania
| | - Dan Nicolae Păduaru
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.,University Emergency Hospital of Bucharest, Bucharest, Romania
| | - Alexandru Constantinescu
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.,University Emergency Hospital of Bucharest, Bucharest, Romania
| | | | - Anca Daniela Stoica
- Babeş-Bolyai University, Cluj-Napoca, Romania.,National Institute for Research and Development of Isotopic and Molecular Technologies, Cluj-Napoca, Romania
| | - Octavian Andronic
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.,University Emergency Hospital of Bucharest, Bucharest, Romania.,Research Institute of the University of Bucharest, Bucharest, Romania
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20
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Kumar S, Mehrotra T, Talukdar D, Verma J, Chandra Karmakar B, Paul S, Chaudhuri S, Kumari Pragasam A, Bakshi S, Kumari S, Chawla M, Purohit A, Porey Karmakar S, Mutreja A, Banerjee S, Ray A, Ramamurthy T, Mukhopadyay AK, Das B. Region-specific genomic signatures of multidrug-resistant Helicobacter pylori isolated from East and South India. Gene 2022; 847:146857. [PMID: 36100116 DOI: 10.1016/j.gene.2022.146857] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 08/08/2022] [Accepted: 08/29/2022] [Indexed: 11/19/2022]
Abstract
Helicobacter pylori is a ubiquitous bacterium and contributes significantly to the burden of chronic gastritis, peptic ulcers, and gastric cancer across the world. Adaptive phenotypes and virulence factors in H. pylori are heterogeneous and dynamic. However, limited information is available about the molecular nature of antimicrobial resistance phenotypes and virulence factors of H. pylori strains circulating in India. In the present study, we analyzed the whole genome sequences of 143 H. pylori strains, of which 32 are isolated from two different regions (eastern and southern) of India. Genomic repertoires of individual strains show distinct region-specific signatures. We observed lower resistance phenotypes and genotypes in the East Indian (Kolkata) H. pylori isolates against amoxicillin and furazolidone antibiotics, whereas higher resistance phenotypes to metronidazole and clarithromycin. Also, at molecular level, a greater number of AMR genes were observed in the east Indian H. pylori isolates as compared to the southern Indian isolates. From our findings, we suggest that metronidazole and clarithromycin antibiotics should be used judicially in the eastern India. However, no horizontally acquired antimicrobial resistance gene was observed in the current H. pylori strains. The comparative genome analysis shows that the number of genes involved in virulence, disease and resistance of H. pylori isolated from two different regions of India is significantly different. Single-nucleotide polymorphisms (SNPs) based phylogenetic analysis distinguished H. pylori strains into different clades according to their geographical locations. Conditionally beneficial functions including antibiotic resistance phenotypes that are linked with faster evolution rates in the Indian isolates.
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Affiliation(s)
- Shakti Kumar
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Tanshi Mehrotra
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Daizee Talukdar
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Jyoti Verma
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Bipul Chandra Karmakar
- Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, India
| | - Sangita Paul
- Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, India
| | - Sujit Chaudhuri
- Department of Gastroenterology, AMRI Hospital, Salt Lake, Kolkata, India
| | - Agila Kumari Pragasam
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Susmita Bakshi
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Shashi Kumari
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Meenal Chawla
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Ayushi Purohit
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Sonali Porey Karmakar
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Ankur Mutreja
- Department of Medicine, Addenbrookes Hospital, University of Cambridge, Cambridge CB20QQ, United Kingdom
| | - Sayantan Banerjee
- Department of Microbiology, All India Institute of Medical Sciences, Kalyani, India
| | - Animesh Ray
- Department of Medicine, All India Institute of Medical Science, New Delhi, India
| | - Thandavarayan Ramamurthy
- Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, India
| | - Asish K Mukhopadyay
- Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, India
| | - Bhabatosh Das
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India.
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21
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Han Y, Long H, Lin Y, He Q, Chen W, Ding X, Zhou L, An P, Wang F, Zhang Z, Hu Y, Li P. Optimized dual therapy for treatment-naive patients of Helicobacter pylori infection: A large-scale prospective, multicenter, open-label, randomized controlled study. Helicobacter 2022; 27:e12922. [PMID: 35939559 PMCID: PMC9541209 DOI: 10.1111/hel.12922] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 07/09/2022] [Accepted: 07/13/2022] [Indexed: 12/19/2022]
Abstract
BACKGROUND The efficacy and safety of high-dose amoxicillin (AMX) and proton pump inhibitors (PPI) dual therapy raises much more attention in recent years. Comparative studies among the dual therapies are required to explore more suitable regimens. This study compared the efficacy, adverse events, and patient compliance of three different high-dose dual regimens in treatment-naive patients of Helicobacter pylori (H. pylori) infection. MATERIALS AND METHODS The study was a prospective, multicenter, open-label, randomized controlled trial, including H. pylori-infected treatment-naive patients at 12 tertiary hospitals in China. The eligible subjects received high-dose AMX and esomeprazole (ESO) dual therapy of different regimens. They were randomly assigned to group A (ESO 20 mg plus AMX 750 mg, Qid for 14 days), group B (ESO 40 mg Bid plus AMX 1 g Tid for 14 days), or group C (ESO 20 mg plus AMX 1 g, Tid for 14 days). The eradication rates, adverse events, and patient compliance of the three groups were compared. RESULTS Between April 2021 and January 2022, a total of 1080 subjects were screened and 945 were randomized. The eradication rates in groups A, B, and C were 88.6% (95% CI 84.5%-91.9%), 84.4% (95% CI 80.0%-88.3%), and 86.7% (95% CI 82.4%-90.2%; p = .315), respectively, based on intention-to-treat analysis; 90.3% (95% CI 86.4%-93.3%), 85.5% (95% CI 81.1%-89.2%), and 87.8% (95% CI 83.6%-91.2%; p = .197), respectively, according to modified intention-to-treat analysis; and 90.4% (95% CI 86.5%-93.5%), 85.8% (95% CI 81.4%-89.5%), and 88.3% (95% CI 84.1%-91.7%; p = .202) in per-protocol analysis. History of antibiotics use in 2 years reduced eradication effect in group B (ESO 40 mg Bid, AMX 1 g Tid). The modified intention-to-treat eradication rates were 81.4% vs 90.0% among those with or without a history of antibiotics use in group B (p = .031). The adverse event rates were 13.7%, 12.7%, and 12.1% in groups A, B, and C, respectively (p = .834). Patient compliance of the three groups was similar. CONCLUSIONS Two optimized AMX and PPI dual regimens (ESO 40 mg Bid or 20 mg Tid plus AMX 1 g Tid for 14 days) had similar efficacy, safety and compliance as compared with classical dual regimen (ESO 20 mg plus AMX 750 mg Qid for 14 days) in H. pylori-infected treatment-naive patients.
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Affiliation(s)
- Ying‐Ying Han
- Division of GastroenterologyTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Hui Long
- Department of GastroenterologyTianyou Hospital Affiliated to Wuhan University of Science and TechnologyWuhanChina
| | - Ya Lin
- Department of GastroenterologyWenchang People's HospitalWenchangChina
| | - Qiong He
- Department of GastroenterologyWuhan Red Cross HospitalWuhanChina
| | - Wei‐Gang Chen
- Department of GastroenterologyThe First Affiliated Hospital of Shihezi University Medical CollegeShiheziChina
| | - Xiang‐Wu Ding
- Department of GastroenterologyWuhan Fourth HospitalWuhanChina
| | - Lin Zhou
- Department of GastroenterologySuizhou Central HospitalSuizhouChina
| | - Ping An
- Department of GastroenterologyRenmin Hospital of Wuhan UniversityWuhanChina
| | - Fen Wang
- Department of GastroenterologyThe Third Xiangya Hospital, Central South UniversityChangshaChina
| | - Zhen‐Yu Zhang
- Department of GastroenterologyNanjing First Hospital, Nanjing Medical UniversityNanjingChina
| | - Yun‐Lian Hu
- Department of GastroenterologyHubei Provincial Hospital of Traditional Chinese MedicineWuhanChina
| | - Pei‐Yuan Li
- Division of GastroenterologyTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina,Department of GastroenterologyWenchang People's HospitalWenchangChina
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22
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Sadeghi H, Narimani T, Tabesh E, Shafiee F, Soltani R. Antibiotic resistance pattern of Helicobacter pylori strains isolated from patients in Isfahan, Iran. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2022; 27:39. [PMID: 35968205 PMCID: PMC9374139 DOI: 10.4103/jrms.jrms_829_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 12/06/2021] [Accepted: 01/31/2022] [Indexed: 11/04/2022]
Abstract
Background The objective of this study was to evaluate the antibiotic resistance pattern of Helicobacter pylori strains isolated from patients in Isfahan province. Materials and Methods Gastric antrum biopsy specimens of patients undergoing endoscopy were cultured. The samples with the growth of H. pylori underwent antibiotic susceptibility test by disk diffusion method. Reaults Of 96 samples, 50 samples (53%) were positive for H. pylori. The rates of antibiotic resistance were as follows: amoxicillin, 6%; azithromycin, 20%; furazolidone, 22%; levofloxacin, 16%; metronidazole, 20%; rifampin, 12%; and tetracycline, 22%. Conclusion H. pylori strains in our area have high rates of resistance to azithromycin, levofloxacin, metronidazole, tetracycline, and furazolidone.
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Affiliation(s)
- Hajarsadat Sadeghi
- Students Research Committee, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Tahmineh Narimani
- Department of Microbiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Elham Tabesh
- Gastroenterology and Hepatology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Fatemeh Shafiee
- Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Rasool Soltani
- Department of Clinical Pharmacy and Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran,Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran,Address for correspondence: Dr. Rasool Soltani, Department of Clinical Pharmacy and Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Hezar-Jerib Avenue, Isfahan, Iran. E-mail:
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23
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Comparative study of endoscopic rapid urease test with serology of helicobacter pylori infection in acid peptic disease. Int J Health Sci (Qassim) 2022. [DOI: 10.53730/ijhs.v6ns3.6360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Acid Peptic Disease (APD) is worldwide health issue for the surgeons, mainly due to risk and associated complications like Gastric Ulcer (GU), Duodenal Ulcer (DU), Gastro intestinal tract (GIT) perforation. This aims at early detection of disease which is caused by Helicobacter Pylori (HP) and intervention prevents the further complications. This study is Cohort study was conducted in the endoscopic unit of Department of General Surgery Tertiary care teaching Hospital over a period of 1 year with a sample size of 121. All the patients suitable for the study in regards to the inclusion and exclusion criteria are subjected to both the study until the sample size is achieved, with the prior agreement of the institutional ethical committee. All the participants are tested with RUT and ELISA and 87.60% had RUT positive and 86.78% had ELISA positive infection. RUT had sensitivity of 87.62% in predicting ELISA, specificity was 12.50%, with a total diagnostic accuracy of 77.69%. We treated 51.24% with the CMO kit and 48.76% with HP kit. O
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24
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Hallur V, Panigrahi M, Sable M, Ghosh M, Mohanty S, Purkait S, Praharaj A. Low clarithromycin resistance in virulent Helicobacter pylori from dyspeptic patients at a tertiary care centre in Odisha. Indian J Med Microbiol 2022; 40:211-216. [DOI: 10.1016/j.ijmmb.2022.02.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Revised: 02/01/2022] [Accepted: 02/26/2022] [Indexed: 11/05/2022]
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25
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Jafar M, Salahuddin M, Khan MSA, Alshehry Y, Alrwaili NR, Alzahrani YA, Imam SS, Alshehri S. Preparation and In Vitro-In Vivo Evaluation of Luteolin Loaded Gastroretentive Microsponge for the Eradication of Helicobacter pylori Infections. Pharmaceutics 2021; 13:2094. [PMID: 34959375 PMCID: PMC8705744 DOI: 10.3390/pharmaceutics13122094] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 11/26/2021] [Accepted: 11/30/2021] [Indexed: 11/17/2022] Open
Abstract
The current study aimed to develop a luteolin gastric floating microsponge for targeting Helicobacter pylori. The microsponge formulations were prepared by a quasi-emulsion method, and then evaluated for various physicochemical variables. The best microsponge was further assessed for drug-polymer interactions, surface morphology, in vivo floating, and in vitro anti H. pylori activity. The formulation which exhibited comparatively good production yield (64.45% ± 0.83), high entrapment efficiency (67.33% ± 3.79), prolonged in vitro floating time (>8 h), and sustained in-vitro drug release was selected as the best microsponge. The SEM study revealed that the best microsponge was spherical in shape and has a porous surface with interconnecting channels. DSC and XRD studies demonstrated the dispersion of luteolin in the polymeric matrix of the microsponge. Ultrasonography confirmed that the best microsponge could in the rat stomach for 4 h. The in vitro MIC results indicate that the anti H. pylori activity of the best microsponge was almost doubled and more sustained compared to pure luteolin. To conclude, it can be said that the developed luteolin gastric floating microsponge could be a better option to effectively eradicate H. pylori infections and the histopathological and pharmacodynamic assessments of our best microsponge can be expected to provide a rewarding outcome.
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Affiliation(s)
- Mohammed Jafar
- Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 34212, Saudi Arabia; (Y.A.); (N.R.A.); (Y.A.A.)
| | - Mohammed Salahuddin
- Department of Clinical Pharmacy Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 34212, Saudi Arabia;
| | - Mohd Sajjad Ahmad Khan
- Department of Basic Sciences, Deanship of Preparatory Year and Supporting Studies, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 34212, Saudi Arabia;
| | - Yasir Alshehry
- Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 34212, Saudi Arabia; (Y.A.); (N.R.A.); (Y.A.A.)
| | - Nazar Radwan Alrwaili
- Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 34212, Saudi Arabia; (Y.A.); (N.R.A.); (Y.A.A.)
| | - Yazeed Ali Alzahrani
- Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 34212, Saudi Arabia; (Y.A.); (N.R.A.); (Y.A.A.)
| | - Syed Sarim Imam
- Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; (S.S.I.); (S.A.)
| | - Sultan Alshehri
- Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; (S.S.I.); (S.A.)
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26
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Molecular Docking of Anti Helicobacter pylori Antibiotics and Proton Pump Inhibitor: A Single Center Survey. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2021. [DOI: 10.22207/jpam.15.4.33] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Helicobacter pylorus (H. pylori) is a deadly bacterium responsible for significant worldwide Gastric Cancer (GC) related mortality. The present study aimed to screen all the anti-microbial drugs used to eradicate H .pylori infection and to identify the most efficient drug by using computational methods through molecular docking analysis. The 3-D structure of protein chorismate synthase of H. pylori was downloaded from the Protein data bank (PDB) online browser. The x-ray crystallography structures of 13 common drugs used against H.pylori infection were also downloaded from the drug bank. We screened all 13 common drugs through molecular docking to know the most efficient binding interaction between the diverse ligand-protein complexes. The results were further compared with clinical survey data from the patients with diverse gastrointestinal H. pylori infected cases. Among the screened compounds, by in-silico approach we found that fluoroquinolone (FLRQ) and tetracycline (TET) manifested more significant interactions with chorismate synthase (CS) protein along with binding energies of -9.2 and -8.1 kcal/mole respectively. Further, the drugs were also corroborated with the survey data from patients with varied gastrointestinal disorders in our study. With this computational study, we could find FLRQ and TET may be the most efficient drug for H. pylori treatment, which can be tried in case of anti H. Pylori treatment failure due to resistance. Hence, effective inter-analysis between the experimental and computational approaches is crucial to build up a strong inhibitor.
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27
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Mehrotra T, Devi TB, Kumar S, Talukdar D, Karmakar SP, Kothidar A, Verma J, Kumari S, Alexander SM, Retnakumar RJ, Devadas K, Ray A, Mutreja A, Nair GB, Chattopadhyay S, Das B. Antimicrobial resistance and virulence in Helicobacter pylori: Genomic insights. Genomics 2021; 113:3951-3966. [PMID: 34619341 DOI: 10.1016/j.ygeno.2021.10.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 09/10/2021] [Accepted: 10/01/2021] [Indexed: 12/26/2022]
Abstract
Microbes evolve rapidly by modifying their genome through mutations or acquisition of genetic elements. Antimicrobial resistance in Helicobacter pylori is increasingly prevalent in India. However, limited information is available about the genome of resistant H. pylori isolated from India. Our pan- and core-genome based analyses of 54 Indian H. pylori strains revealed plasticity of its genome. H. pylori is highly heterogenous both in terms of the genomic content and DNA sequence homology of ARGs and virulence factors. We observed that the H. pylori strains are clustered according to their geographical locations. The presence of point mutations in the ARGs and absence of acquired genetic elements linked with ARGs suggest target modifications are the primary mechanism of its antibiotic resistance. The findings of the present study would help in better understanding the emergence of drug-resistant H. pylori and controlling gastric disorders by advancing clinical guidance on selected treatment regimens.
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Affiliation(s)
- Tanshi Mehrotra
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - T Barani Devi
- Microbiome Laboratory, Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India
| | - Shakti Kumar
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Daizee Talukdar
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Sonali Porey Karmakar
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Akansha Kothidar
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Jyoti Verma
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Shashi Kumari
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Sneha Mary Alexander
- Microbiome Laboratory, Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India
| | - R J Retnakumar
- Microbiome Laboratory, Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India
| | - Krishnadas Devadas
- Department of Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India
| | - Animesh Ray
- Department of Medicine, All India Institute of Medical, Science, New Delhi, India
| | - Ankur Mutreja
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India; Department of Medicine, Addenbrookes Hospital, University of Cambridge, Cambridge CB20QQ, United Kingdom
| | - G Balakrish Nair
- Microbiome Laboratory, Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India
| | - Santanu Chattopadhyay
- Microbiome Laboratory, Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India.
| | - Bhabatosh Das
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India.
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Cui R, Song Z, Suo B, Tian X, Xue Y, Meng L, Niu Z, Jin Z, Zhang H, Zhou L. Correlation Analysis Among Genotype Resistance, Phenotype Resistance and Eradication Effect of Helicobacter pylori. Infect Drug Resist 2021; 14:1747-1756. [PMID: 34012273 PMCID: PMC8127322 DOI: 10.2147/idr.s305996] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 04/15/2021] [Indexed: 12/13/2022] Open
Abstract
Background It has not been fully confirmed whether the detection of Helicobacter pylori resistance gene mutation can replace antibiotic drug sensitivity test to guide the clinical individualized treatment. Therefore, we have studied this aspect and discussed the application value of antibiotic sensitivity gene test. Materials and Methods The biopsy specimen of gastric mucosa from the patients examined by endoscopy and positive for rapid urease test were collected continuously for histopathological analysis, H. pylori culture, antibiotic drug sensitivity test (E-test drug sensitivity test), and antibiotic sensitivity gene test (high-throughput nucleotide sequencing). The participants received triple plus bismuth solution eradication treatment (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, twice daily for 14 days) for follow-up, and the eradication effect was determined. Results The 551/602 subjects, who met the inclusion criteria, were subjected to culture for H. pylori and antibiotic drug sensitivity determination; among them 506 were cultured successfully. The results showed that the resistance rates of H. pylori were 38.9% for clarithromycin and 31.0% for levofloxacin. In 489 H. pylori strains, the mutations were detected in clarithromycin and levofloxacin resistance genes, indicating the genotype resistance. The resistance genes of clarithromycin and levofloxacin were consistent with phenotype resistance with respect to sensitivity (81.2% and 69.7% for clarithromycin and levofloxacin, respectively) and specificity (88.9% and 93.7% for clarithromycin and levofloxacin, respectively). The eradication rate of H. pylori in the clarithromycin-resistant group was significantly lower than that in the sensitive group (ITT: 52.1% vs 85.0%, P < 0.001). Conclusion A correlation was established between the resistance genes of clarithromycin and levofloxacin and their phenotypic resistance and clinical efficacy. The detection of H. pylori resistance genes has a good clinical application prospect.
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Affiliation(s)
- Rongli Cui
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Zhiqiang Song
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Baojun Suo
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Xueli Tian
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Yan Xue
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Lingmei Meng
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Zhanyue Niu
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Zhu Jin
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Hejun Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Liya Zhou
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
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Bahmaninejad P, Ghafourian S, Mahmoudi M, Maleki A, Sadeghifard N, Badakhsh B. Persister cells as a possible cause of antibiotic therapy failure in Helicobacter pylori. JGH OPEN 2021; 5:493-497. [PMID: 33860100 PMCID: PMC8035453 DOI: 10.1002/jgh3.12527] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 02/12/2021] [Accepted: 02/22/2021] [Indexed: 01/31/2023]
Abstract
Background and Aim Due to the failure of antibiotic treatment and recurrence of infection in patients with Helicobacter pylori, this study was designed to find the possible cause of treatment failure and recurrence of the H. pylori infections in Ilam, Iran. Methods One hundred patients with specific symptoms of H. pylori infection were selected, and after taking a biopsy specimen, identification of H. pylori, antibiotic susceptibility assay, and persister cell assay were performed. In addition, after treatment, patients with persister cells were followed for possible recurrence of infection. Furthermore, an antibiotic susceptibility assay was performed. Results Our results demonstrated that, among 100 patients, 50% (n = 50) showed positive results for the existence of H. pylori. Among the susceptible isolates, 18% (n = 9) were persister cells that were sensitive to clarithromycin as confirmed by a 5 folds higher than the Minimal Inhibitory Concentration (MIC) of clarithromycin. The data were confirmed by following up the suspected patients. Conclusion Our results demonstrated that persister cells in H. pylori infections may be responsible to recurrent infection and antibiotic treatment failure. However, more research is needed to obtain more information in this area.
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Affiliation(s)
- Parvin Bahmaninejad
- Department of Microbiology, Faculty of Medicine Ilam University of Medical Sciences Ilam Iran
| | - Sobhan Ghafourian
- Department of Microbiology, Faculty of Medicine Ilam University of Medical Sciences Ilam Iran
| | - Mina Mahmoudi
- Department of Microbiology, Faculty of Medicine Ilam University of Medical Sciences Ilam Iran
| | - Abbas Maleki
- Clinical Microbiology Research Center Ilam University of Medical Sciences Ilam Iran
| | - Nourkhoda Sadeghifard
- Department of Microbiology, Faculty of Medicine Ilam University of Medical Sciences Ilam Iran
| | - Behzad Badakhsh
- Department of Gastroenterology, Faculty of Medicine Ilam University of Medical Sciences Ilam Iran
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30
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Qumar S, Nguyen TH, Nahar S, Sarker N, Baker S, Bulach D, Ahmed N, Rahman M. A comparative whole genome analysis of Helicobacter pylori from a human dense South Asian setting. Helicobacter 2021; 26:e12766. [PMID: 33073485 PMCID: PMC7816255 DOI: 10.1111/hel.12766] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 08/31/2020] [Accepted: 09/20/2020] [Indexed: 12/23/2022]
Abstract
Helicobacter pylori, a Gram-negative bacterium, is associated with a wide range of gastric diseases such as gastritis, duodenal ulcer, and gastric cancer. The prevalence of H pylori and risk of disease vary in different parts of the world based on the prevailing bacterial lineage. Here, we present a contextual and comparative genomics analysis of 20 clinical isolates of H pylori from patients in Bangladesh. Despite a uniform host ethnicity (Bengali), isolates were classified as being part of the HpAsia2 (50%) or HpEurope (50%) population. Out of twenty isolates, eighteen isolates were cagA positive, with two HpEurope isolates being cagA negative, three EPIYA motif patterns (AB, AB-C, and ABC-C) were observed among the cagA-positive isolates. Three vacA genotypes were observed with the s1m1i1dic1 genotype observed in 75% of isolates; the s1m2i1d1c2 and s2m2i2d2c2 genotypes were found to be 15% and 10% of isolates, respectively. The non-virulent genotypes s2m2i2d2c2 was only observed in HpEurope population isolates. Genotypic analysis of oipA gene, present in all isolates, revealed five different patterns of the CT repeat; all HpAsia2 isolates were in "ON" while 20% of HpEurope isolates were genotypically "OFF." The three blood group antigen binding adhesins encoded genes (bab genes) examined and we observed that the most common genotype was (babA/babB/-) found in eight isolates, notably six were HpAsia2 isolates. The babA gene was found in all HpAsia2 isolates but present in only half of the HpEurope isolates. In silico antibiotic susceptibility analysis revealed that 40% of the strains were multi-drug resistant. Mutations associated with resistance to metronidazole, fluoroquinolone, and clarithromycin were detected 90%, 45%, and 5%, respectively, in H pylori strain. In conclusion, it is evident that two populations of H pylori with similar antibiotic profiles are predominant in Bangladesh, and it appears that genotypically the HpAisa2 isolates are potentially more virulent than the HpEurope isolates.
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Affiliation(s)
- Shamsul Qumar
- Department of Biotechnology and BioinformaticsUniversity of HyderabadHyderabadIndia
| | - Trang Hoa Nguyen
- The Hospital for Tropical DiseasesOxford University Clinical Research UnitHo Chi Minh CityVietnam
| | - Shamsun Nahar
- International Center for Diarrhoeal Disease Research BangladeshDhakaBangladesh
| | - Nishat Sarker
- International Center for Diarrhoeal Disease Research BangladeshDhakaBangladesh
| | - Stephen Baker
- Cambridge Institute of Therapeutic Immunology & Infectious DiseaseCambridge UniversityCambridgeUK
| | - Dieter Bulach
- The University of Melbourne and The Peter Doherty Institute for Infection and ImmunityMelbourneVICAustralia
| | - Niyaz Ahmed
- Department of Biotechnology and BioinformaticsUniversity of HyderabadHyderabadIndia,International Center for Diarrhoeal Disease Research BangladeshDhakaBangladesh
| | - Motiur Rahman
- The Hospital for Tropical DiseasesOxford University Clinical Research UnitHo Chi Minh CityVietnam,Centre for Tropical Medicine and Global HealthNuffield Department of Clinical MedicineOxford UniversityOxfordUK
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Zhou JJ, Shi X, Zheng SP, Tang D, Cai T, Yao Y, Wang F. Efficacy of bismuth-based quadruple therapy for eradication of Helicobacter pylori infection based on previous antibiotic exposure: A large-scale prospective, single-center clinical trial in China. Helicobacter 2020; 25:e12755. [PMID: 32914914 DOI: 10.1111/hel.12755] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 07/29/2020] [Accepted: 08/06/2020] [Indexed: 01/30/2023]
Abstract
OBJECTIVE This study aims to evaluate the efficacy and safety of three bismuth-based quadruple regimens for eradication of Helicobacter pylori (H pylori) infection in a large number of H pylori-positive patients with or without previous eradication therapy. METHODS Consecutive adult patients with H pylori infection, regardless of previous eradication therapy, were eligible for the present study. Three bismuth-based quadruple regimens were selected according to the past history of antibiotics use: (A) esomeprazole, amoxicillin, clarithromycin, and colloidal bismuth tartrate; (B) esomeprazole, amoxicillin, furazolidone, and colloidal bismuth tartrate; and (C) esomeprazole, doxycycline, furazolidone, and colloidal bismuth tartrate. All patients received a 14-day course of treatment, and 13 C/14 C urea breath test was utilized at four weeks after the completion of treatment to determine the H pylori eradication. Then, the eradication rates were calculated in terms of intention-to-treat (ITT) and per-protocol (PP) analyses. Adverse events (AEs) were recorded during the treatment. RESULTS Overall, 1,226 patients were recruited, and 331, 57, and 838 patients were allocated to receive regimens A, B, and C, respectively. The H pylori eradication rates were 84.0%, 82.5%, and 82.9% (ITT) and 94.6%, 92.2%, and 93.7% (PP), respectively, in regimens A, B, and C. However, there was no significant difference among these three regimens. The incidence of AEs was 4.6% for all patients during the study, that is, 3.3%, 10.5%, and 4.7% for regimens A, B, and C, respectively. All AEs were mild and recovered at the follow-up visit. CONCLUSION All three bismuth-based quadruple regimens based on the previous antibiotic use can achieve satisfactory eradication rates for H pylori infection and are safe.
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Affiliation(s)
- Jing-Jing Zhou
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.,Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Xiao Shi
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.,Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Shao-Peng Zheng
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.,Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Dan Tang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.,Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Ting Cai
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.,Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Yao Yao
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.,Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Fen Wang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.,Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, China
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The Potential Benefits of Vonoprazan as Helicobacter pylori Infection Therapy. Pharmaceuticals (Basel) 2020; 13:ph13100276. [PMID: 32998241 PMCID: PMC7600708 DOI: 10.3390/ph13100276] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 09/24/2020] [Accepted: 09/24/2020] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori infection is a severe global health problem that is closely associated with acid-related diseases and gastric malignancies. Eradicating H. pylori is strongly recommended for lowering peptic ulcer recurrence and preventing gastric cancer. The current approved H. pylori eradication regimen combines a proton pump inhibitor (PPI) with two antibiotics. Unfortunately, this regimen failed to meet expectations mostly due to antibiotic resistance and insufficient gastric acid suppression. Vonoprazan, a novel potassium-competitive acid blocker, showed promising results as a PPI replacement. Vonoprazan inhibits gastric acid secretion by acting as a reversible competitive inhibitor against potassium ions and forming disulfide bonds with the cysteine molecule of H+/K+-ATPase. Vonoprazan has superior pharmacological characteristics over PPI, such as no requirement for acid activation, stability in acidic conditions, shorter optimum acid suppression period, and resistance to cytochrome P (CYP)2C19 polymorphism. Several comparative randomized controlled trials and meta-analyses revealed the superiority of vonoprazan in eradicating H. pylori, notably the resistant strains. The adverse effect caused by vonoprazan is long-term acid suppression that may induce elevated gastrin serum, hypochlorhydria, and malabsorption. All vonoprazan studies have only been conducted in Japan. Further studies outside Japan are necessary for universally conclusive results.
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O'Connor A, Furuta T, Gisbert JP, O'Morain C. Review - Treatment of Helicobacter pylori infection 2020. Helicobacter 2020; 25 Suppl 1:e12743. [PMID: 32918350 DOI: 10.1111/hel.12743] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
This review summarizes important studies regarding Helicobacter pylori therapy published from April 2019 to April 2020. The main themes that emerge involve studies assessing antibiotic resistance, and there is also growing momentum behind the utility of vonoprazan as an alternative to proton pump inhibitor (PPI) therapy and also bismuth-based regimens as a first-line regimen. Antibiotic resistance is rising wherever it is being assessed, and clarithromycin resistance in particular has reached a point where it may no longer be a viable therapy without previous testing in many regions of the world. The evidence for the efficacy of a bismuth-based quadruple therapy as a first-line therapy is now very clearly established, and there is substantial evidence that it is the best performing first-line therapy. The utility of vonoprazan as an alternative to PPI therapy, especially in resistant and difficult-to-treat groups, has also been considered in great detail this year, and it may offer an opportunity in the near future to reduce the problem of antibiotic resistance.
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Affiliation(s)
- Anthony O'Connor
- Department of Gastroenterology, Tallaght University Hospital/Trinity College, Dublin, Ireland
| | - Takahisa Furuta
- The Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Colm O'Morain
- Department of Gastroenterology, Tallaght University Hospital/Trinity College, Dublin, Ireland
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Lok CH, Zhu D, Wang J, Ren YT, Jiang X, Li SJ, Zhao XY. Phenotype and Molecular Detection of Clarithromycin and Levofloxacin Resistance in Helicobacter pylori Clinical Isolates in Beijing. Infect Drug Resist 2020; 13:2145-2153. [PMID: 32753910 PMCID: PMC7352368 DOI: 10.2147/idr.s249370] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Accepted: 06/15/2020] [Indexed: 12/12/2022] Open
Abstract
Introduction Understanding drug resistance is important in drug selection for Helicobacter pylori (H. pylori) eradication, and drug resistance data are lacking in Beijing. Purpose This cross-sectional study aimed to isolate H. pylori from patients with gastroduodenal diseases and to analyze drug resistance to clarithromycin (CLA) and levofloxacin (LEV), which are used frequently in China. Patients and Methods One hundred and seventy-six patients with gastroduodenal diseases undergoing gastroduodenoscopy were selected by convenient sampling. Gastric mucosa samples were cultured and sub-cultured using a new medium broth. Active H. pylori strains were confirmed by microscopy observation as Gram-negative curved bacilli with positive test results for urease, oxidase, and catalase, and H. pylori 16S rRNA amplification by polymerase chain reaction (PCR). CLA and LEV resistance was identified by minimum inhibitory concentration (MIC) tests and sequencing of 23S rRNA, gyrA, and gyrB genes. Results From the 176 clinical samples, 112 (112/176, 63.6%) were confirmed with H. pylori infection and 65 (65/176, 36.9%) active H. pylori strains were obtained and further confirmed by MIC assay. Overall, the rates of CLA-resistant and LEV-resistant mutations in the 112 samples were 50.9% and 33.0%, respectively. Mutation related to CLA resistance was A2143G in the 23S rRNA gene and mutations associated with LEV resistance were N87K, D91G, and D91Y in the gyrA gene. Of 112 samples, 22 (19.6%) presented dual resistance to CLA and LEV. Resistance of the H. pylori strains to CLA (r=0.846, P<0.001) and LEV (r=0.936, P<0.001) had a strong correlation in phenotypic and genotypic level. Conclusion The results indicated that resistance of CLA and LEV is severe among patients with gastroduodenitis. A good consistency could be found as to drug resistance between genotypic or phenotypic assay, suggested extending the detection of H. pylori drug resistance from the MIC method to a genotypic assay.
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Affiliation(s)
- Chong-Hou Lok
- Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People's Republic of China
| | - Dong Zhu
- Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People's Republic of China
| | - Jia Wang
- Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People's Republic of China
| | - Yu-Tang Ren
- Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People's Republic of China
| | - Xuan Jiang
- Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People's Republic of China
| | - Shu-Jun Li
- Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People's Republic of China
| | - Xiu-Ying Zhao
- Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People's Republic of China
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Mori H, Suzuki H. Update on quinolone-containing rescue therapies for Helicobacter pylori infection. World J Gastroenterol 2020; 26:1733-1744. [PMID: 32351290 PMCID: PMC7183861 DOI: 10.3748/wjg.v26.i15.1733] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 03/05/2020] [Accepted: 04/04/2020] [Indexed: 02/06/2023] Open
Abstract
Third generation of quinolones, such as levofloxacin and moxifloxacin, -containing regimens are often used in second-line or rescue treatment of Helicobacter pylori infection. However, the increasing antibiotic resistance to quinolones affects the efficacies of quinolones-containing therapies in recent years. Therefore, there is a need to enhance the effectiveness of quinolones-containing therapies. Sitafloxacin, a fourth-generation quinolone, and vonoprazan, a novel potassium-competitive acid blocker, are now available as more effective treatment options. The aim of this paper is to summarize the current evidence of quinolone-containing therapies in rescue treatments, and to discuss the importance of drug sensitivity tests or analysis of gyrA mutation before treatments.
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Affiliation(s)
- Hideki Mori
- Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven 3000, Belgium
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara 259-1193, Japan
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Boyanova L, Hadzhiyski P, Kandilarov N, Markovska R, Mitov I. Multidrug resistance in Helicobacter pylori: current state and future directions. Expert Rev Clin Pharmacol 2019; 12:909-915. [PMID: 31424296 DOI: 10.1080/17512433.2019.1654858] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Introduction: Helicobacter pylori antibiotic resistance has increased worldwide and multidrug resistance (MDR), which seriously hampers eradication success of the frequent chronic infection, has often been reported. Areas covered: H. pylori MDR rates are discussed, mostly from recent articles published since 2015. Present approaches and future directions to counteract the MDR are outlined. Expert opinion: Alarming presence of triple, quadruple and, in some studies, quintuple and sextuple resistance was detected. Primary MDR rates ranged from <10% in most European countries to >40% in Peru. Post-treatment or overall MDR rates were >23-36% in about half of the studies. MDR prevalence has varied both among and within the countries. Factors linked to the MDR are national antibiotic consumption, antibiotic misuse, treatment failures and bacterial factors such as mutations, efflux pumps, and biofilms. Important directions to counteract the MDR increase can be optimization of present and new eradication regimens, wider use of bismuth-containing regimens, assessment of benefit of vonoprazan, new antibiotics such as newer fluoroquinolones and oxazolidinone analogues, adjuvants involving N-acetylcysteine and probiotics, anti-biofilm approaches using anti-biofilm peptides and rhamnolipid and development of vaccines and non-invasive tests for resistance detection. However, more efforts and studies are required. Strain susceptibility testing is increasingly important.
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Affiliation(s)
- Lyudmila Boyanova
- Department of Medical Microbiology, Medical University of Sofia , Sofia , Bulgaria
| | - Petyo Hadzhiyski
- Specialized Hospital for Active Pediatric Treatment, Medical University of Sofia , Sofia , Bulgaria
| | - Nayden Kandilarov
- Department of General and Hepatobiliary Pancreatic Surgery, Department of Surgery, Medical University , Sofia , Bulgaria
| | - Rumyana Markovska
- Department of Medical Microbiology, Medical University of Sofia , Sofia , Bulgaria
| | - Ivan Mitov
- Department of Medical Microbiology, Medical University of Sofia , Sofia , Bulgaria
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