|
1
|
Rocha GR, Lemos FFB, Silva LGDO, Luz MS, Correa Santos GL, Rocha Pinheiro SL, Calmon MS, de Melo FF. Overcoming antibiotic-resistant Helicobacter pylori infection: Current challenges and emerging approaches. World J Gastroenterol 2025; 31:102289. [PMID: 40093672 PMCID: PMC11886534 DOI: 10.3748/wjg.v31.i10.102289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 11/28/2024] [Accepted: 01/17/2025] [Indexed: 02/26/2025] Open
Abstract
Recent studies have shown a noticeable increase in global Helicobacter pylori (H. pylori) resistance, with clarithromycin resistance surpassing 15% in various areas. However, inadequate epidemiological monitoring, especially in developing countries, and the absence of uniform testing methods lead to discrepancies between regions and a possible underestimation of resistance levels. The complexity of treating H. pylori is driven by its highly dynamic genome, which is prone to frequent mutations contributing to phenotypical resistance. The usual course of action in empirical treatment involves using a combination of various drugs simultaneously, leading to significant resistance selection pressure and potential side effects. The emergence of H. pylori strains resistant to multiple drugs is closely tied to failures in first-line treatment, highlighting the need to prevent further resistance by using optimal initial empirical therapy or regimens guided by antibiotic susceptibility testing, requiring a collection of mixed samples and multiple isolates for accurate assessment. The emergence of new treatments like potassium-competitive acid blockers offers a hopeful approach to decrease antimicrobial usage while still ensuring effectiveness in comparison to traditional therapies with proton pump inhibitors. Additionally, the use of probiotics is under investigation to identify specific strains and formulations that may mitigate therapy-associated adverse effects.
Collapse
Affiliation(s)
- Gabriel Reis Rocha
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Fabian Fellipe Bueno Lemos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | | | - Marcel Silva Luz
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Gabriel Lima Correa Santos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Samuel Luca Rocha Pinheiro
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Mariana Santos Calmon
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| |
Collapse
|
|
2
|
Bharathi P, Wang SF. Rare earth orthovanadate (REM-VO 4; REM = Pr, Gd, and Sm)-based sensors for selective and simultaneous detection of furazolidone and metronidazole. NANOSCALE 2025; 17:5907-5924. [PMID: 39907024 DOI: 10.1039/d4nr04594g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
Abstract
Antibiotics are vital tools in the fight against bacterial infections, with furazolidone (FD) and metronidazole (MD) being widely used to target pathogens like G. lamblia and H. pylori. However, overuse of these antibiotics can lead to serious health complications, highlighting the urgent need for accurate, real-time detection of these drugs at precise levels. In this study, we explore the use of differential pulse voltammetry (DPV) for detecting FD and MD with high sensitivity, employing a dual detection method. To enhance detection, we developed a sensor using rare earth metal-based orthovanadates (REM-VO4, where REM = Pr, Gd, and Sm) as electrode modifiers. These materials offer exceptional surface control, boosting the sensor's sensitivity and selectivity. Among the different configurations, the SmVO4-modified glassy carbon electrode (SmV/GCE) stands out, demonstrating the lowest charge transfer resistance (Rct = 56.82 Ω) and the largest electrochemical surface area (A = 0.11 cm2). SmVO4's unique nanostructure, with its high electrochemically active surface area and hollow structure, is key to its impressive performance. This sensor not only provides the lowest limits of detection (0.0009 μM for FD and 0.0036 μM for MD individually, and 0.0015 μM and 0.0049 μM for simultaneous detection) but also shows excellent anti-interference, repeatability, and reproducibility. Furthermore, SmV/GCE has been successfully applied for real-time analysis of biological and environmental samples, offering recoveries between 97.33 to 99.60%, demonstrating its practical potential for precise antibiotic monitoring.
Collapse
Affiliation(s)
- Pandiyan Bharathi
- Department of Materials and Mineral Resources Engineering, National Taipei University of Technology, Taipei 106, Taiwan.
| | - Sea-Fue Wang
- Department of Materials and Mineral Resources Engineering, National Taipei University of Technology, Taipei 106, Taiwan.
| |
Collapse
|
|
3
|
Abdulrahman MS, Mansy MS, Al-Ghreib KA, Johar D, Zaky S. PCR-based RFLP and ERIC-PCR patterns of Helicobacter pylori strains linked to multidrug resistance in Egypt. Sci Rep 2024; 14:22273. [PMID: 39333134 PMCID: PMC11436738 DOI: 10.1038/s41598-024-72289-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: 10/21/2023] [Accepted: 09/05/2024] [Indexed: 09/29/2024] Open
Abstract
H. pylori infects approximately 50% of the world's population that causes chronic gastritis, and may lead to peptic ulcer disease (PUD). H. pylori-induced chronic infections are associated with gastric adenocarcinoma and low-grade gastric lymphoma. In Egypt, H. pylori strains are widespread and became resistant to antimicrobial agents, thus advanced typing methods are needed to differentiate infectious strains that are resistant to antibiotics, and therefore earlier prognosis and infection control. The main objectives were (i) to determine susceptibility of infectious H. pylori strains to some antimicrobial agents that are currently used in eradication therapy in Egypt; (ii) to identify diverse strains commonly detected in the gastrointestinal (GIT) endoscopy units in Egypt through phenotypic and genotypic analyses. In this observational study we isolated 167 isolates from 232 gastric biopsies (antrum and corpus) of patients who were admitted to the upper GIT endoscopy units in five governmental Egyptian hospitals. Antimicrobial susceptibility patterns were investigated using Kirby Bauer disc diffusion and agar dilution Minimum Inhibitory Concentrations (MICs) methods. Phenotypic characterization was based on biotyping and antibiogram typing techniques. Genotypic characterization was carried out using PCR-based Restriction Fragment Length Polymorphism (RFLP) and Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR analyses. H. pylori isolates were highly resistant to diverse antimicrobial agents including Metronidazole, Fluoroquinolones, Macrolides, Amoxycillin, Tetracycline and Gentamicin. Two factors contributed to the increased resistance of H. pylori to the conventional therapy seen in Egypt: (i) Metronidazole and Amoxycillin are inexpensive and available drugs being abused by patients; (ii) the regional prescribing practice of Macrolids commonly used to treat upper respiratory and urinary tract infections. Five different biotypes were identified depending on the ability of the isolates to synthesize different enzymes. Nine antibiogram types were identified. PCR-RFLP analysis revealed fifteen different fingerprints while ERIC-PCR revealed 22 fingerprints. Biotyping alone or in combination with antibiogram typing are highly useful molecular tools in the prognosis of strain relatedness. PCR-RFLP and ERIC-PCR acquired good discriminatory power for identifying H. pylori infectious sub-types.
Collapse
Affiliation(s)
- Mohammed S Abdulrahman
- Microbiology and Immunology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
| | - Moselhy S Mansy
- Microbiology and Immunology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
| | - Kamel A Al-Ghreib
- Microbiology and Immunology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
| | - Dina Johar
- Department of Biochemistry and Nutrition, Faculty of Women for Arts, Sciences and Education, Ain Shams University, Heliopolis, Cairo, Egypt.
| | - Samy Zaky
- Hepatogastroenterology and Infectious Diseases Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| |
Collapse
|
|
4
|
Pan Z, Zhou C, Bai X, Wang F, Hong J, Fang JY, Huang Y, Sheng C. Discovery of New Fusobacterium nucleatum Inhibitors to Attenuate Migratory Capability of Colon Cancer Cells by the Drug Repositioning Strategy. J Med Chem 2023; 66:15699-15714. [PMID: 37983010 DOI: 10.1021/acs.jmedchem.3c00281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2023]
Abstract
Recent studies revealed that intestinal microbiota played important roles in colorectal cancer (CRC) carcinogenesis. Particularly, Fusobacterium nucleatum was confirmed to promote the proliferation and metastasis of CRC. Therefore, targeting F. nucleatum may be a potential preventive and therapeutic approach for CRC. Herein, 2,272 off-patent drugs were screened inhibitory activity against F. nucleatum. Among the hits, nitisinone was identified as a promising anti-F. nucleatum lead compound. Further optimization of nitisinone led to the discovery of more potent derivatives. Particularly, compounds 19q and 22c showed potent anti-F. nucleatum activity (MIC50 = 1 and 2 μg/mL, respectively) with low cytotoxicity. Among them, compound 19q effectively attenuated the migratory ability of MC-38 cells induced by F. nucleatum. Preliminary mechanism studies suggested that nitisinone and its derivatives might act by downregulating nitroreductase and tryptophanase. Thus, the development of small molecule F. nucleatum inhibitors represents an effective strategy to treat CRC.
Collapse
Affiliation(s)
- Zhizhi Pan
- College of Pharmacy, Dali University, Xueren Road 2, Dali 671000, China
| | - Chenchen Zhou
- College of Pharmacy, Dali University, Xueren Road 2, Dali 671000, China
| | - Xuexin Bai
- The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China
| | - Fangfang Wang
- The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China
| | - Jie Hong
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Jing-Yuan Fang
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Yahui Huang
- The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China
| | - Chunquan Sheng
- The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China
| |
Collapse
|
|
5
|
Buzás GM, Birinyi P. Newer, Older, and Alternative Agents for the Eradication of Helicobacter pylori Infection: A Narrative Review. Antibiotics (Basel) 2023; 12:946. [PMID: 37370265 DOI: 10.3390/antibiotics12060946] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 05/10/2023] [Accepted: 05/19/2023] [Indexed: 06/29/2023] Open
Abstract
Although discovered 40 years ago, Helicobacter pylori infection is still raising diagnostic and therapeutic problems today. The infection is currently managed based on statements in several guidelines, but implementing them in practice is a long process. Increasing antibiotic resistance and weak compliance of the patients limit the efficacy of eradication regimens, leaving much room for improvement. Third-generation proton pump inhibitors have added little to the results of the first two generations. Potassium-competitive acid blockers have a stronger and longer inhibitory action of acid secretion, increasing the intragastric pH. They obtained superior results in eradication when compared to proton pump inhibitors. Instead of innovative antibiotics, derivatives of existing antimicrobials were developed; some new fluoroquinolones and nitazoxanide seem promising in practice, but they are not recommended by the guidelines. Carbonic anhydrase inhibitors have both anti-secretory and bactericidal effects, and some researchers are expecting their revival in the treatment of infection. Capsules containing components of the eradication regimens have obtained excellent results, but are of limited availability. Probiotics, if containing bacteria with anti-Helicobacter pylori activity, may be useful, increasing the rates of eradication and lowering the prevalence and severity of the side effects.
Collapse
Affiliation(s)
- György Miklós Buzás
- Ferencváros Health Centre, Gastroenterology, Mester utca 45, 1095 Budapest, Hungary
- Medoc Health Centre, Gastroenterology, Lehel út 8, 1137 Budapest, Hungary
| | - Péter Birinyi
- Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Szentkirályi utca 46, 1086 Budapest, Hungary
| |
Collapse
|
|
6
|
Bordin DS, Voynovan IN, Sarsenbaeva AS, Zaytsev OV, Abdulkhakov RA, Bakulina NV, Bakulin IG, Osipenko MF, Livzan MA, Alekseenko SA, Tarasova LV, Tarasova GN, Bogomolov PO, Maev IV, Andreev DN, Abdulkhakov SR, Starostin BD, Bakanova NV, Kononova AG, Kolbasnikov SV, Bueverova EL, Moreira L, Megraud F, O'Morain C, Perez Nyssen O, Gisbert J. [Effectiveness of empirical Helicobacter pylori eradication therapy with furazolidone in Russia: results from the European Registry on Helicobacter pylori Management (Hp-EuReg)]. TERAPEVT ARKH 2023; 95:120-129. [PMID: 37167127 DOI: 10.26442/00403660.2023.02.202107] [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: 03/29/2023] [Accepted: 03/29/2023] [Indexed: 05/13/2023]
Abstract
BACKGROUND First-line therapy does not always provide a high level of Helicobacter pylori eradication due to the increase of H. pylori resistance to antibiotics; therefore, it remains necessary to identify the most effective rescue treatments. The purpose of this study was to evaluate the efficacy and safety of empirical H. pylori furazolidone-containing regimens. MATERIALS AND METHODS Adult H. pylori infected patients empirically treated with furazolidone-containing eradication regimens were registered in an international, prospective, multicenter non-intervention European registry on H. pylori management (Hp-EuReg). Data were collected at AEG-REDCap e-CRF from 2013 to 2021 and the quality was reviewed. Modified intention-to-treat (mITT) effectiveness analyses were performed. RESULTS Overall 106 patients received empirical furazolidone-containing therapy in Russia. Furazolidone was prescribed in a sequential scheme along with amoxicillin, clarithromycin and a proton pump inhibitor in 68 (64%) cases, triple regimens were prescribed in 28 (26%) patients and quadruple regimens in 10 (9.4%). Treatment duration of 7 days was assigned to 2 (1.9%) patients, 10-day eradication therapy in case of 80 (75%) and 14 days - in 24 (23%) patients. Furazolidone was mainly used in first- (79%) and second-line (21%) regimens. The methods used to diagnose H. pylori infection were: histology (81%), stool antigen test (64%), 13C-urea breath test (6.6%), and rapid urease test (1.9%). The mITT effectiveness of sequential therapy was 100%; 93% with the triple therapy and 75.5% with quadruple therapy. Compliance was reported in 98% of cases. Adverse events were revealed in 5.7% of patients, mostly nausea (3.8%). No serious adverse events were reported. CONCLUSION Furazolidone containing eradication regimens appear to be an effective and safe empirical therapy in Russia.
Collapse
Affiliation(s)
- D S Bordin
- Loginov Moscow Clinical Scientific Center
- Yevdokimov Moscow State University of Medicine and Dentistry
- Tver State Medical University
| | | | | | | | | | - N V Bakulina
- Mechnikov North-Western State Medical University
| | - I G Bakulin
- Mechnikov North-Western State Medical University
| | | | | | | | | | | | - P O Bogomolov
- Yevdokimov Moscow State University of Medicine and Dentistry
- Private Medical Center "Universal"
- Vladimirsky Moscow Regional Clinical Research Institute
| | - I V Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - D N Andreev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | | | | | | | | | | | - E L Bueverova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - L Moreira
- Hospital Clínic de Barcelona
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd)
- University of Barcelona
| | | | | | - O Perez Nyssen
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)
- Universidad Autónoma de Madrid (UAM)
| | - J Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)
- Universidad Autónoma de Madrid (UAM)
| |
Collapse
|
|
7
|
Celiberto F, Losurdo G, Pricci M, Girardi B, Marotti A, Di Leo A, Ierardi E. The State of the Art of Molecular Fecal Investigations for Helicobacter pylori ( H. pylori) Antibiotic Resistances. Int J Mol Sci 2023; 24:4361. [PMID: 36901792 PMCID: PMC10002064 DOI: 10.3390/ijms24054361] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/18/2023] [Accepted: 02/21/2023] [Indexed: 02/25/2023] Open
Abstract
A new paradigm shift for the treatment of Helicobacter pylori (H. pylori) infection would be timely due to a progressive increase in antibiotic resistance. Such a shift in the perspective of the H. pylori approach should include the preliminary assessment of antibiotic resistance. However, the availability of sensitivity tests is not widespread and the guidelines have always indicated empirical treatments without taking into account the need to make sensitivity tests accessible, i.e., the necessary starting point for improving results in different geographical areas. Currently, the traditional tools for this purpose (culture) are based on performing an invasive investigation (endoscopy) and often involve technical difficulties; thus, they were only confined to the settings where multiple attempts at eradication have failed. In contrast, genotypic resistance testing of fecal samples using molecular biology methods is much less invasive and more acceptable to patients. The purpose of this review is to update the state of the art of molecular fecal susceptibility testing for the management of this infection and to extensively discuss the potential benefits of their large-scale deployment, i.e., novel pharmacological opportunities.
Collapse
Affiliation(s)
- Francesca Celiberto
- Section of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, Italy
- Course in Organs and Tissues Transplantation and Cellular Therapies, Department of Precision Medicine Jonic Area, University “Aldo Moro” of Bari, 70124 Bari, Italy
| | - Giuseppe Losurdo
- Section of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, Italy
| | | | | | - Angela Marotti
- Section of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, Italy
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, Italy
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, Italy
| |
Collapse
|
|
8
|
Seyedmajidi MR, Hosseini SA, Vafaeimanesh J. Comparing the Effect of Two Low-dose and High-dose Four-drug Regimens of Furazolidone in Eradicating Helicobacter Pylori. Middle East J Dig Dis 2021; 13:131-138. [PMID: 34712451 PMCID: PMC8531922 DOI: 10.34172/mejdd.2021.216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 02/07/2021] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Antibiotic resistance is a major cause of Helicobacter pylori (H. pylori ) treatment failures. The increased resistance to clarithromycin and metronidazole has reduced the ability of this therapeutic regimen and prompted researchers to look for other drugs. One of the antibiotics of interest in this regard is furazolidone because of its low drug resistance. The aim of this study is compare two-drug regimens including low-dose and high-dose furazolidone in the treatment of H. pylori. METHODS This study is a clinical trial in which the studied subjects were categorized into two groups. The first group underwent treatment with amoxicillin 1000 mg-BD, furazolidone 100 mg-BD, omeprazole 20 mg-BD, and bismuth subcitrate 240 mg-BD for two weeks (low-dose OFAB). The second group received furazolidone 200 mg-BD (high-dose OFAB). Then eight weeks after completion of the treatment, they were examined in terms of eradication via the UBT test. RESULTS 85 participants completed the study in each group. The response to treatment was 76% and 83% in the low and high-dose groups, respectively, based on intention to treat analysis. Based on per protocol analysis the response to treatment was 78% and 84%, respectively, if excluded patients had completed their protocol and had response to treatment, and 72% and 79%, respectively, if excluded patients had completed their protocol and did not have response to treatment (p = 0.298). In the low-dose and high-dose groups, 16.5% and 24.7% of the participants suffered the complications of treatment with furazolidone (p = 0.18), respectively. Three patients in the high-dose group and one in the low-dose group did not complete the treatment because of the medication's bad taste (p = 0.03). CONCLUSION Low doses of furazolidone had a comparable therapeutic effect compared with high doses, but patients experienced significantly lower levels of bad taste, which was a major cause of reluctance to continue treatment. Therefore, we think four-drug low-dose furazolidone treatment is a good choice in eradicating H. pylori.
Collapse
Affiliation(s)
- Mohammad Reza Seyedmajidi
- Golestan Research Center of Gastroenterology and Hepatology-GRCGH (GOUMS), Golestan University of Medical Sciences, Gorgan, Iran
| | - Seyed Ashkan Hosseini
- Golestan Research Center of Gastroenterology and Hepatology-GRCGH (GOUMS), Golestan University of Medical Sciences, Gorgan, Iran
| | - Jamshid Vafaeimanesh
- Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Sciences, Qom, Iran Clinical Research Development Center, Shahid Beheshti Hospital, Qom University of Medical Sciences, Qom, Iran
| |
Collapse
|
|
9
|
Tshibangu-Kabamba E, Yamaoka Y. Helicobacter pylori infection and antibiotic resistance - from biology to clinical implications. Nat Rev Gastroenterol Hepatol 2021; 18:613-629. [PMID: 34002081 DOI: 10.1038/s41575-021-00449-x] [Citation(s) in RCA: 277] [Impact Index Per Article: 69.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/31/2021] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori is a major human pathogen for which increasing antibiotic resistance constitutes a serious threat to human health. Molecular mechanisms underlying this resistance have been intensively studied and are discussed in this Review. Three profiles of resistance - single drug resistance, multidrug resistance and heteroresistance - seem to occur, probably with overlapping fundamental mechanisms and clinical implications. The mechanisms that have been most studied are related to mutational changes encoded chromosomally and disrupt the cellular activity of antibiotics through target-mediated mechanisms. Other biological attributes driving drug resistance in H. pylori have been less explored and this could imply more complex physiological changes (such as impaired regulation of drug uptake and/or efflux, or biofilm and coccoid formation) that remain largely elusive. Resistance-related attributes deployed by the pathogen cause treatment failures, diagnostic difficulties and ambiguity in clinical interpretation of therapeutic outcomes. Subsequent to the increasing antibiotic resistance, a substantial drop in H. pylori treatment efficacy has been noted globally. In the absence of an efficient vaccine, enhanced efforts are needed for setting new treatment strategies and for a better understanding of the emergence and spread of drug-resistant bacteria, as well as for improving diagnostic tools that can help optimize current antimicrobial regimens.
Collapse
Affiliation(s)
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Oita, Japan. .,Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX, USA.
| |
Collapse
|
|
10
|
Resina E, Gisbert JP. Rescue Therapy with Furazolidone in Patients with at Least Five Eradication Treatment Failures and Multi-Resistant H. pylori infection. Antibiotics (Basel) 2021; 10:antibiotics10091028. [PMID: 34572610 PMCID: PMC8467492 DOI: 10.3390/antibiotics10091028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 08/12/2021] [Accepted: 08/18/2021] [Indexed: 12/21/2022] Open
Abstract
Helicobacter pylori infection may persist after multiple eradication treatments. The aim of this study was to evaluate the efficacy and safety of a furazolidone-based rescue regimen in hyper-refractory patients. A unicentre, prospective study was designed. Patients in whom five or more treatments had consecutively failed were included. All patients had previously received bismuth and key antibiotics, such as amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifabutin, and had positive H. pylori culture, demonstrating resistance to clarithromycin, metronidazole, and levofloxacin. A quadruple regimen with furazolidone (200 mg), amoxicillin (1 g), bismuth (240 mg), and esomeprazole (40 mg) was prescribed twice a day for 14 days. Eradication was confirmed by the stool antigen test. Compliance was determined through questioning, and adverse effects using a questionnaire. Eight patients (mean age 56 years, 63% men, 38% peptic ulcer disease, 12% gastric cancer precursor lesions, and 50% functional dyspepsia) were included. Per-protocol and intention-to-treat eradication rates were 63%. Compliance was 100%. Adverse effects were reported in two (25%) patients, and all were mild. Even after five or more previous H. pylori eradication failures, and a multi-resistant infection, rescue treatment with furazolidone may be effective in approximately two-thirds of the cases, constituting a valid strategy after multiple previous eradication failures with key antibiotics such as clarithromycin, metronidazole, tetracycline, levofloxacin, and rifabutin.
Collapse
|
|
11
|
Singh SP, Ahuja V, Ghoshal UC, Makharia G, Dutta U, Zargar SA, Venkataraman J, Dutta AK, Mukhopadhyay AK, Singh A, Thapa BR, Vaiphei K, Sathiyasekaran M, Sahu MK, Rout N, Abraham P, Dalai PC, Rathi P, Sinha SK, Bhatia S, Patra S, Ghoshal U, Poddar U, Mouli VP, Kate V. Management of Helicobacter pylori infection: The Bhubaneswar Consensus Report of the Indian Society of Gastroenterology. Indian J Gastroenterol 2021; 40:420-444. [PMID: 34219211 DOI: 10.1007/s12664-021-01186-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 04/20/2021] [Indexed: 02/04/2023]
Abstract
The Indian Society of Gastroenterology (ISG) felt the need to organize a consensus on Helicobacter pylori (H. pylori) infection and to update the current management of H. pylori infection; hence, ISG constituted the ISG's Task Force on Helicobacter pylori. The Task Force on H. pylori undertook an exercise to produce consensus statements on H. pylori infection. Twenty-five experts from different parts of India, including gastroenterologists, pathologists, surgeons, epidemiologists, pediatricians, and microbiologists participated in the meeting. The participants were allocated to one of following sections for the meeting: Epidemiology of H. pylori infection in India and H. pylori associated conditions; diagnosis; treatment and retreatment; H. pylori and gastric cancer, and H. pylori prevention/public health. Each group reviewed all published literature on H. pylori infection with special reference to the Indian scenario and prepared appropriate statements on different aspects for voting and consensus development. This consensus, which was produced through a modified Delphi process including two rounds of face-to-face meetings, reflects our current understanding and recommendations for the diagnosis and management of H. pylori infection. These consensus should serve as a reference for not only guiding treatment of H. pylori infection but also to guide future research on the subject.
Collapse
Affiliation(s)
- Shivaram Prasad Singh
- Department of Gastroenterology, Srirama Chandra Bhanja Medical College and Hospital, Cuttack, 753 007, India.
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226 014, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Usha Dutta
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Showkat Ali Zargar
- Department of Gastroenterology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, 190 011, India
| | - Jayanthi Venkataraman
- Department of Hepatology, Sri Ramachandra Medical Centre, No. 1 Ramachandra Nagar, Porur, Chennai, 600 116, India
| | - Amit Kumar Dutta
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore, 632 004, India
| | - Asish K Mukhopadhyay
- Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, 700 010, India
| | - Ayaskanta Singh
- Department of Gastroenterology, IMS and Sum Hospital, Bhubaneswar, 756 001, India
| | - Babu Ram Thapa
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Superspeciality of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Kim Vaiphei
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160 012, India
| | - Malathi Sathiyasekaran
- Department of Pediatric Gastroenterology, Kanchi Kamakoti Childs Trust Hospital, Chennai, 600 034, India
| | - Manoj K Sahu
- Department of Gastroenterology, IMS and Sum Hospital, Bhubaneswar, 756 001, India
| | - Niranjan Rout
- Department of Pathology, Acharya Harihar Post Graduate Institute of Cancer, Manglabag, Cuttack, 753 007, India
| | - Philip Abraham
- P D Hinduja Hospital and Medical Research Centre, Veer Savarkar Marg, Cadel Road, Mahim, Mumbai, 400 016, India
| | - Prakash Chandra Dalai
- Gastro and Kidney Care Hospital, IRC Village, Nayapalli, Bhubaneswar, 751 015, India
| | - Pravin Rathi
- Department of Gastroenterology, Topiwala National Medical College and B Y L Nair Charitable Hospital, Dr Anandrao Laxman Nair Marg, Mumbai, 400 008, India
| | - Saroj K Sinha
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Shobna Bhatia
- Department of Gastroenterology and Hepatobiliary Sciences, Sir HN Reliance Foundation Hospital and Research Centre, Raja Rammohan Roy Road, Prarthana Samaj, Girgaon, Mumbai, 400 004, India
| | - Susama Patra
- Department of Pathology, All India Institute of Medical Sciences, Patrapada, Bhubaneswar, 751 019, India
| | - Ujjala Ghoshal
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226 014, India
| | - Ujjal Poddar
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | | | - Vikram Kate
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, 605 006, India
| |
Collapse
|
|
12
|
Rasi-Bonab F, Jafari-Sales A, Shaverdi MA, Navidifar T, Saki M, Ghorbani A, Adekanmbi AO, Jafari B, Naebi S. Antibiotic resistance pattern and frequency of cagA and vacA genes in Helicobacter pylori strains isolated from patients in Tabriz city, Iran. BMC Res Notes 2021; 14:216. [PMID: 34059110 PMCID: PMC8165783 DOI: 10.1186/s13104-021-05633-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Accepted: 05/25/2021] [Indexed: 01/14/2023] Open
Abstract
Objective Helicobacter pylori is one of the most common causes of gastric infections in humans. It is estimated that approximately 50% of people around the world are infected with this bacterium. This study aimed to determine the antibiotic resistance pattern, as well as the frequency of cagA and vacA genes in H. pylori isolates obtained from patients in the clinical centers in Tabriz city, Iran. Results The culture method detected 100 (45.25%) H. pylori isolates from 221 biopsy samples during 3 years. The results showed that 63% and 81% of the isolates were positive for cagA and vacA genes, respectively. The highest resistance of isolates was seen against metronidazole (79%) and amoxicillin (36%), respectively. Also, the isolates showed the least resistance to tetracycline (8%).
Collapse
Affiliation(s)
- Farnaz Rasi-Bonab
- Department of Microbiology, Marand Branch, Islamic Azad University, Marand, Iran
| | - Abolfazl Jafari-Sales
- Department of Microbiology, School of Basic Sciences, Kazerun Branch, Islamic Azad University, Kazerun, Iran.
| | - Mohammad Amin Shaverdi
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran. .,Khuzestan Blood Transfusion Center, Abadan, Iran.
| | | | - Morteza Saki
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Atosa Ghorbani
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Abimbola Olumide Adekanmbi
- Environmental Microbiology and Biotechnology Laboratory, Department of Microbiology, University of Ibadan, Ibadan, Nigeria
| | - Behboud Jafari
- Department of Microbiology, Ahar Branch, Islamic Azad University, Ahar, Iran
| | - Sara Naebi
- Department of Microbiology, Ahar Branch, Islamic Azad University, Ahar, Iran
| |
Collapse
|
|
13
|
Allegra A, Imbesi C, Bitto A, Ettari R. Drug Repositioning for the Treatment of Hematologic Disease: Limits, Challenges and Future Perspectives. Curr Med Chem 2021; 28:2195-2217. [PMID: 33138750 DOI: 10.2174/0929867327999200817102154] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 07/21/2020] [Accepted: 07/21/2020] [Indexed: 11/22/2022]
Abstract
Drug repositioning is a strategy to identify new uses for approved or investigational drugs that are used off-label outside the scope of the original medical indication. In this review, we report the most relevant studies about drug repositioning in hematology, reporting the signalling pathways and molecular targets of these drugs, and describing the biological mechanisms which are responsible for their anticancer effects. Although the majority of studies on drug repositioning in hematology concern acute myeloid leukemia and multiple myeloma, numerous studies are present in the literature on the possibility of using these drugs also in other hematological diseases, such as acute lymphoblastic leukemia, chronic myeloid leukemia, and lymphomas. Numerous anti-infectious drugs and chemical entities used for the therapy of neurological or endocrine diseases, oral antidiabetics, statins and medications used to treat high blood pressure and heart failure, bisphosphonate and natural substance such as artemisin and curcumin, have found a place in the treatment of hematological diseases. Moreover, several molecules drastically reversed the resistance of the tumor cells to the chemotherapeutic drugs both in vitro and in vivo.
Collapse
Affiliation(s)
- Alessandro Allegra
- Department of Human Pathology in Adulthood and Childhood, University of Messina, Messina, Italy
| | - Chiara Imbesi
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Alessandra Bitto
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Roberta Ettari
- Department of Chemical, Biological, Pharmaceutical and Environmental Chemistry, University of Messina, Messina, Italy
| |
Collapse
|
|
14
|
Abinaya M, Muthuraj V. Bi-functional catalytic performance of silver manganite/polypyrrole nanocomposite for electrocatalytic sensing and photocatalytic degradation. Colloids Surf A Physicochem Eng Asp 2020. [DOI: 10.1016/j.colsurfa.2020.125321] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
|
|
15
|
Kim SJ, Chung JW, Woo HS, Kim SY, Kim JH, Kim YJ, Kim KO, Kwon KA, Park DK. Two-week bismuth-containing quadruple therapy and concomitant therapy are effective first-line treatments for Helicobacter pylori eradication: A prospective open-label randomized trial. World J Gastroenterol 2019; 25:6790-6798. [PMID: 31857780 PMCID: PMC6920663 DOI: 10.3748/wjg.v25.i46.6790] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 12/01/2019] [Accepted: 12/06/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Increasing levels of antibiotic resistance have reduced the Helicobacter pylori (H. pylori) eradication rates afforded by the standard triple therapy. Thus, 2-wk first-line four-drug regimens must be considered.
AIM To analyze the eradication rates of modified bismuth-containing quadruple therapy (mBCQT) and concomitant therapy (CT), the associated adverse events, and compliance.
METHODS Patients infected with H. pylori were prospectively randomized to receive mBCQT or CT for 2 wk. mBCQT featured a proton pump inhibitor (PPI), bismuth, metronidazole, and tetracycline, taken twice daily. CT included a PPI, clarithromycin, metronidazole, and amoxicillin, taken twice daily. The 13C-urea breath test was performed no earlier than 4 wk after therapy concluded to confirm eradication. If either the histological or rapid urease test was positive, H. pylori infection was diagnosed.
RESULTS The demographic characteristics of 68 patients who received mBCQT and 68 who received CT did not differ significantly. On intention-to-treat analysis, the eradication rate was 88.2% (60/68) in the mBCQT group and 79.4% (54/68) in the CT group (P = 0.162). By per-protocol analysis, the respective eradication rates were 98.4% (60/61) and 93.1% (54/58) (P = 0.199). More CT than mBCQT patients experienced adverse events [33.8% (23/68) mBCQT vs 51.5% (35/58) CT patients, respectively, P = 0.037]. All patients showed good compliance [85.3% (58/68) mBCQT vs 82.4% (56/68) CT patients, P = 0.641].
CONCLUSION The H. pylori eradication rates of the 2-wk mBCQT and CT regimens are high. Most patients show good compliance, and more CT than mBCQT patients experience adverse events.
Collapse
Affiliation(s)
- So Jeong Kim
- College of Medicine, Gachon University Graduate School of Medicine, Incheon 21936, South Korea
| | - Jun-Won Chung
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, South Korea
| | - Hyun Sun Woo
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, South Korea
| | - Su Young Kim
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, South Korea
| | - Jung Ho Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, South Korea
| | - Yoon Jae Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, South Korea
| | - Kyoung Oh Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, South Korea
| | - Kwang An Kwon
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, South Korea
| | - Dong Kyun Park
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, South Korea
| |
Collapse
|
|
16
|
Concomitant and controlled release of furazolidone and bismuth(III) incorporated in a cross-linked sodium alginate-carboxymethyl cellulose hydrogel. Int J Biol Macromol 2019; 126:359-366. [DOI: 10.1016/j.ijbiomac.2018.12.136] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 12/12/2018] [Accepted: 12/16/2018] [Indexed: 02/08/2023]
|
|
17
|
Zhang YW, Hu WL, Cai Y, Zheng WF, Du Q, Kim JJ, Kao JY, Dai N, Si JM. Outcomes of furazolidone- and amoxicillin-based quadruple therapy for Helicobacter pylori infection and predictors of failed eradication. World J Gastroenterol 2018; 24:4596-4605. [PMID: 30386109 PMCID: PMC6209572 DOI: 10.3748/wjg.v24.i40.4596] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2018] [Revised: 08/16/2018] [Accepted: 10/05/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the outcomes of furazolidone- and amoxicillin-based quadruple therapy for treatment of Helicobacter pylori (H. pylori) infection and identify predictors of failed eradication.
METHODS Patients with H. pylori infection treated with furazolidone, amoxicillin, bismuth, and proton pump inhibitor therapy (January 2015 to December 2015) who received the 13C-urea breath test > 4 wk after treatment were evaluated. Demographic and clinical data including prior H. pylori treatment attempts, medication adherence, alcohol and cigarette consumption during therapy, and treatment-related adverse events were recorded by reviewing medical records and telephone surveys. H. pylori eradication rates for overall and subgroups were evaluated. Multivariate analysis was performed to identify independent predictors of failed H. pylori eradication.
RESULTS Of the 992 patients treated and retested for H. pylori infection, the overall eradication rate was 94.5% [95% confidence interval (CI): 94.1%-95.9%]. H. pylori eradication rate of primary therapy was 95.0% (95%CI: 93.5%-96.5%), while that of rescue therapy was 91.3% (95%CI: 86.8%-95.8%). Among the 859 patients who completed the study protocol, 144 (17%) reported treatment-related adverse events including 24 (3%) leading to premature discontinuation. On multivariate analysis, poor medication adherence [adjusted odds ratio (AOR) = 6.7, 95%CI: 2.8-15.8], two or more previous H. pylori treatments (AOR = 7.4, 95%CI: 2.2-24.9), alcohol consumption during therapy (AOR = 4.4, 95%CI: 1.5-12.3), and possibly smoking during therapy (AOR = 1.9, 95%CI: 0.9-4.3) were associated with failed H. pylori eradication.
CONCLUSION Furazolidone- and amoxicillin-based quadruple therapy for H. pylori infection in an area with a high prevalence of clarithromycin resistance demonstrated high eradication rates as primary and rescue therapies with a favorable safety profile. Patient education targeting abstinence from alcohol during therapy and strict medication adherence may further optimize H. pylori eradication.
Collapse
Affiliation(s)
- Ya-Wen Zhang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
- Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Wei-Ling Hu
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
- Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Yuan Cai
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Wen-Fang Zheng
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
- Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Qin Du
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
| | - John J Kim
- Division of Gastroenterology, Loma Linda University, Loma Linda, CA 92354, United States
| | - John Y Kao
- Division of Gastroenterology, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, United States
| | - Ning Dai
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Jian-Min Si
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
- Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| |
Collapse
|
|
18
|
Zhuge L, Wang Y, Wu S, Zhao RL, Li Z, Xie Y. Furazolidone treatment for Helicobacter Pylori infection: A systematic review and meta-analysis. Helicobacter 2018; 23:e12468. [PMID: 29480532 DOI: 10.1111/hel.12468] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Antibiotic resistance is a major cause of Helicobacter pylori (H. pylori) treatment failures. Because the resistance rate of H. pylori to furazolidone is low, we aimed to assess the efficacy and safety of furazolidone. We searched the PubMed, Web of Science, Cochrane Library, and Embase databases and included randomized controlled trials (RCT) that either compared furazolidone to other antibiotics or changed the administered dose of furazolidone. A total of 18 articles were included in the meta-analysis. According to the intention-to-treat (ITT) analysis, the total eradication rates of furazolidone-containing therapy were superior to those of other antibiotic-containing therapies (relative risk [RR] 1.07, 95% confidence interval [CI] 1.01-1.14) (13 RCTs). Specifically, the eradication rates of furazolidone-containing therapy were better than those for metronidazole-containing therapy (RR 1.10, 95% CI: 1.01-1.21 for ITT). The eradication rate of furazolidone-containing bismuth-containing quadruple therapy was 92.9% (95% CI: 90.7%-95.1%) (PP). In addition, a higher daily dose of furazolidone increased the eradication rate (RR 1.17, 95% CI: 1.05-1.31). And the incidence of some adverse effects, such as fever and anorexia, was higher in the furazolidone group than in the control group, the overall incidences of total side effects and severe side effects showed no significant differences between the groups. Furazolidone-containing treatments could achieve satisfactory eradication rates and did not increase the incidence of total or severe adverse effects, but the incidence of milder side effects, such as fever and anorexia, should be considered when prescribing furazolidone-containing treatments to patients.
Collapse
Affiliation(s)
- Liya Zhuge
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Youhua Wang
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Shuang Wu
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Ru-Lin Zhao
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.,Department of Biochemistry and Molecular Biology, Jiangxi Academy of Medical Science, Jiangxi, China
| | - Zhen Li
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.,The Medical College of Nanchang University, Nanchang, Jiangxi Province, China
| | - Yong Xie
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| |
Collapse
|
|
19
|
Mohammadi M, Attaran B, Malekzadeh R, Graham DY. Furazolidone, an Underutilized Drug for H. pylori Eradication: Lessons from Iran. Dig Dis Sci 2017; 62:1890-1896. [PMID: 28577244 PMCID: PMC5527993 DOI: 10.1007/s10620-017-4628-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Accepted: 05/23/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Treatment success of H. pylori eradication therapy has declined worldwide largely because of increased antimicrobial resistance. New therapeutic approaches are needed, especially for countries like Iran, where resistance to commonly used drugs is already widespread and traditional H. pylori therapies produce poor cure rates. AIM To review the results of quadruple therapy trials containing bismuth and furazolidone in Iran. METHODS We searched PubMed, Google scholar as well as the references of all published papers for studies conducted in Iran, utilizing furazolidone in the treatment of H. pylori infections. The target population was four drug studies that utilized a combination of bismuth, furazolidone, amoxicillin, or tetracycline plus a proton pump inhibitor. RESULTS Eighteen studies with 22 arms including 1713 subjects were found. The weighted mean cure rate for 14-day studies (six studies) using 200 mg b.i.d. furazolidone was 80% intention to treat (ITT) and 87% per protocol (PP). Studies using 100 mg b.i.d. (three studies) were less effective (weighted mean ITT cure rate = 67%). One small 14-day study with furazolidone 100 mg q.i.d. achieved cure rates of 94.5% ITT and PP. CONCLUSIONS Although furazolidone-bismuth quadruple therapy proved relatively effective in Iran, furazolidone-containing regimens remain to be optimized. Based on these data and results from China, it appears likely that 14-day therapy containing furazolidone 100 mg t.i.d. or q.i.d. is likely to provide the highest cure rates with lowest side effects; this remains to be experimentally tested. Detailed suggestions for further development of furazolidone-containing regimens are provided.
Collapse
Affiliation(s)
- Marjan Mohammadi
- HPGC Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran Tehran, Iran
| | - Bahareh Attaran
- HPGC Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran Tehran, Iran
| | - Reza Malekzadeh
- Digestive Disease Research Center, Digestive Disease Research Institute Tehran University of Medical Sciences
| | - David Y. Graham
- Department of Medicine, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, TX USA
| |
Collapse
|
|
20
|
Dai C, Li D, Gong L, Xiao X, Tang S. Curcumin Ameliorates Furazolidone-Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells by Inhibiting ROS Production and Mitochondrial Pathway. Molecules 2016; 21:E1061. [PMID: 27556439 PMCID: PMC6272881 DOI: 10.3390/molecules21081061] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2016] [Revised: 08/08/2016] [Accepted: 08/10/2016] [Indexed: 12/11/2022] Open
Abstract
Furazolidone (FZD), a synthetic nitrofuran derivative, has been widely used as an antibacterial and antiprotozoal agent. Recently, the potential toxicity of FZD has raised concerns, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on FZD-induced cytotoxicity and the underlying mechanism in human hepatocyte L02 cells. The results showed that curcumin pre-treatment significantly ameliorated FZD-induced oxidative stress, characterized by decreased reactive oxygen species (ROS) and malondialdehyde formation, and increased superoxide dismutase, catalase activities and glutathione contents. In addition, curcumin pre-treatment significantly ameliorated the loss of mitochondrial membrane potential, the activations of caspase-9 and -3, and apoptosis caused by FZD. Alkaline comet assay showed that curcumin markedly reduced FZD-induced DNA damage in a dose-dependent manner. Curcumin pre-treatment consistently and markedly down-regulated the mRNA expression levels of p53, Bax, caspase-9 and -3 and up-regulated the mRNA expression level of Bcl-2. Taken together, these results reveal that curcumin protects against FZD-induced DNA damage and apoptosis by inhibiting oxidative stress and mitochondrial pathway. Our study indicated that curcumin may be a promising combiner with FZD to reduce FZD-related toxicity in clinical applications.
Collapse
Affiliation(s)
- Chongshan Dai
- College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China.
| | - Daowen Li
- College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China.
| | - Lijing Gong
- Sport Science Research Center, Beijing Sport University, 48 Xinxi Road, Haidian District, Beijing 100084, China.
| | - Xilong Xiao
- College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China.
| | - Shusheng Tang
- College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China.
| |
Collapse
|
|
21
|
|
|
22
|
Talebi Bezmin Abadi A. Furazolidone and Helicobacter pylori Treatment. Middle East J Dig Dis 2015; 7:110-111. [PMID: 26106473 PMCID: PMC4430792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Accepted: 02/08/2014] [Indexed: 11/21/2022] Open
Affiliation(s)
- Amin Talebi Bezmin Abadi
- Assistant Professor, Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| |
Collapse
|
|
23
|
Abstract
Helicobacter pylori (H. pylori) infection has been associated with gastric disorders. The situation of H. pylori infection in China-where a high prevalence of H. pylori infection, a high incidence of gastric cancer, and widespread resistance to clarithromycin, metronidazole, and levofloxacin exist-is quite different from that in Western countries. In order for Chinese clinicians to better manage H. pylori infection, a Chinese Study Group on H. pylori published four consensus reports regarding the management of H. pylori infection in China between 1999 and 2012. The eradication rate with standard triple therapy was <80% in most areas of China. Bismuth is available in China, and bismuth-containing quadruple therapy has been shown to produce a high eradication rate; thus, bismuth quadruple therapy could be recommended both as an initial and as a rescue therapy in China. There is no advantage of sequential therapy over triple therapy in Chinese patients, but the efficacy of concomitant therapy must be studied further. This review introduces the epidemiology, diagnosis, indicators, and therapies for the eradication of H. pylori in China in recent years.
Collapse
Affiliation(s)
- Chuan Xie
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China
| | | |
Collapse
|
|
24
|
Ergun M, Dengiz C, Özer MS, Şahin E, Balci M. Synthesis of thio- and furan-fused heterocycles: furopyranone, furopyrrolone, and thienopyrrolone derivatives. Tetrahedron 2014. [DOI: 10.1016/j.tet.2014.05.071] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
|
|
25
|
Furazolidone-Based Quadruple Therapy for Eradication of Helicobacter pylori Infection in Peptic Ulcer Disease. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2014. [DOI: 10.5812/archcid.18549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
|
|
26
|
Bang CS, Baik GH. Attempts to enhance the eradication rate of Helicobacter pylori infection. World J Gastroenterol 2014; 20:5252-5262. [PMID: 24833855 PMCID: PMC4017040 DOI: 10.3748/wjg.v20.i18.5252] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Revised: 10/17/2013] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
Increasing rates of antimicrobial resistance to clarithromycin and metronidazole present challenges in maintaining optimal eradication rates. Knowledge of local antibiotic resistance and consumption pattern is important in selecting a reliable regimen. In addition, adverse effect profiles of therapeutic regimens are important and must be addressed to enhance compliance rates. Various methods of enhancing the eradication rates of Helicobacter pylori (H. pylori) have been investigated, including changing combinations or durations of established drugs, adding adjuvant drugs, or development of new molecules or agents. Bismuth-containing quadruple, sequential, concomitant, and levofloxacin-based triple therapies are replacing the long-standing standard of the triple regimen. Despite the encouraging results of these regimens, individualized approaches like treatment after antibiotics resistance test or CYP2C19 genotyping would be the mainstream of future therapy. Because scientific, economic, and technical problems make these advance therapies unfit for widespread use, future development for H. pylori therapy should be directed to overcome individualized antibiotic resistance. Although various novel regimens and additive agents have indicated favorable outcomes, more studies or validations are needed to become a mainstream H. pylori therapy.
Collapse
|
|
27
|
Navidifar T, Eslami G, Akhondi M, Baghbanian M, Fallah Zadeh H, Zandi H. Antibacterial Resistance Patterns of Helicobacter pylori Clinical Isolates From Gastric Biopsy of Patients in Yazd. INTERNATIONAL JOURNAL OF ENTERIC PATHOGENS 2014. [DOI: 10.17795/ijep17791] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
|
|
28
|
Kanizaj TF, Kunac N. Helicobacter pylori: Future perspectives in therapy reflecting three decades of experience. World J Gastroenterol 2014; 20:699-705. [PMID: 24574743 PMCID: PMC3921479 DOI: 10.3748/wjg.v20.i3.699] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 12/05/2013] [Accepted: 01/02/2014] [Indexed: 02/06/2023] Open
Abstract
The rising prevalence of antibiotic resistance has created a need to reassess the established Helicobacter pylori (H. pylori) eradication protocols, and to develop new ones. Various bacterial and host factors are evaluated, and their contribution to eradication failure is estimated. For a long time being considered the cornerstone eradication scheme, the standard triple therapy has been replaced with novel, more efficient regimens, namely sequential and concomitant, along with the emergence of a new design of bismuth quadruple therapy. A rescue levofloxacin based regimen has overcome the fear of therapy failure due to higher prevalence of dual resistant (clarithromycin and metronidazole) H. pylori. Culture-free and efficient susceptibility test are reestablishing the concept of tailored therapy, making eradication success close to originally desirable rates. Alleviating therapy side effects and improving patient compliance are as important as choosing appropriate eradication schemes, so various probiotic compound supplements are taken into consideration. Finally, we summarize the emerging efforts and obstacles in creating efficient H. pylori vaccine.
Collapse
|
|
29
|
Ierardi E, Giorgio F, Losurdo G, Di Leo A, Principi M. How antibiotic resistances could change Helicobacter pylori treatment: A matter of geography? World J Gastroenterol 2013; 19:8168-8180. [PMID: 24363506 PMCID: PMC3857438 DOI: 10.3748/wjg.v19.i45.8168] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Revised: 10/18/2013] [Accepted: 11/03/2013] [Indexed: 02/06/2023] Open
Abstract
Therapeutic management of Helicobacter pylori (H. pylori) remains an unsolved issue. Indeed, no therapeutic regimen is able to cure the infection in all treated patients, and in many the infection persists despite the administration of several consecutive standard therapies. Although antibiotic resistance reports describe alarming results, the outcome of therapeutic regimens does not seem to parallel this scenario in most cases, since a successful performance is often reached in more than 80% of cases. However, the phenomenon of increasing antibiotic resistance is being closely studied, and the results show controversial aspects even in the same geographic area. For the continents of Europe, America, Asia, Africa, and Oceania, minimal and maximal values of resistance to the main antibiotics (clarithromycin, amoxicillin, metronidazole, and levofloxacin) feature wide ranges in different countries. The real enigma is therefore linked to the several different therapeutic regimens, which show results that often do not parallel the in vitro findings even in the same areas. A first aspect to be emphasized is that some regimens are limited by their use in very small geographic districts. Moreover, not all therapeutic trials have considered bacterial and host factors affecting the therapeutic outcome. The additional use of probiotics may help to reduce adverse events, but their therapeutic impact is doubtful. In conclusion, the "ideal therapy", paradoxically, appears to be a "utopia", despite the unprecedented volume of studies in the field and the real breakthrough in medical practice made by the discovery and treatment of H. pylori. The ample discrepancies observed in the different areas do not encourage the development of therapeutic guidelines that could be valid worldwide. On these bases, one of the main challenges for the future might be identifying a successful solution to overcome antibiotic resistances. In this context, geography must be considered a relevant matter.
Collapse
|
|
30
|
Jiang X, Sun L, Qiu JJ, Sun X, Li S, Wang X, So CWE, Dong S. A novel application of furazolidone: anti-leukemic activity in acute myeloid leukemia. PLoS One 2013; 8:e72335. [PMID: 23951311 PMCID: PMC3739762 DOI: 10.1371/journal.pone.0072335] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2013] [Accepted: 07/08/2013] [Indexed: 12/11/2022] Open
Abstract
Acute myeloid leukemia (AML) is the most common malignant myeloid disorder of progenitor cells in myeloid hematopoiesis and exemplifies a genetically heterogeneous disease. The patients with AML also show a heterogeneous response to therapy. Although all-trans retinoic acid (ATRA) has been successfully introduced to treat acute promyelocytic leukemia (APL), it is rather ineffective in non-APL AML. In our present study, 1200 off-patent marketed drugs and natural compounds that have been approved by the Food and Drug Administration (FDA) were screened for anti-leukemia activity using the retrovirus transduction/transformation assay (RTTA). Furazolidone (FZD) was shown to inhibit bone marrow transformation mediated by several leukemia fusion proteins, including AML1-ETO. Furazolidone has been used in the treatment of certain bacterial and protozoan infections in human and animals for more than sixty years. We investigated the anti-leukemic activity of FZD in a series of AML cells. FZD displayed potent antiproliferative properties at submicromolar concentrations and induced apoptosis in AML cell lines. Importantly, FZD treatment of certain AML cells induced myeloid cell differentiation by morphology and flow cytometry for CD11b expression. Furthermore, FZD treatment resulted in increased stability of tumor suppressor p53 protein in AML cells. Our in vitro results suggest furazolidone as a novel therapeutic strategy in AML patients.
Collapse
MESH Headings
- Animals
- Antineoplastic Agents/pharmacology
- Antitrichomonal Agents/pharmacology
- Apoptosis/drug effects
- Biological Assay
- Cell Differentiation/drug effects
- Cell Line, Tumor
- Dose-Response Relationship, Drug
- Drug Repositioning
- Furazolidone/pharmacology
- Gene Expression
- Humans
- Leukemia, Myeloid, Acute/drug therapy
- Leukemia, Myeloid, Acute/genetics
- Leukemia, Myeloid, Acute/pathology
- Oncogene Proteins, Fusion/genetics
- Oncogene Proteins, Fusion/metabolism
- Retroviridae/genetics
- Tumor Suppressor Protein p53/genetics
- Tumor Suppressor Protein p53/metabolism
Collapse
Affiliation(s)
- Xueqing Jiang
- Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Wuhan, Hubei, China
- Department of Medicine and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America
| | - Lin Sun
- Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Wuhan, Hubei, China
- Department of Medicine and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America
| | - Jihui Julia Qiu
- Department of Medicine and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America
- Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, United States of America
| | - Xiujing Sun
- Department of Medicine and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America
| | - Sen Li
- Department of Medicine and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America
| | - Xiyin Wang
- Department of Medicine and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America
| | - Chi Wai Eric So
- Department of Haematological Medicine, King’s College London, Denmark Hill, London, United Kingdom
| | - Shuo Dong
- Department of Medicine and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America
| |
Collapse
|
|
31
|
Coelho LG, Maguinilk I, Zaterka S, Parente JM, do Carmo Friche Passos M, Moraes-Filho JPP. 3rd Brazilian Consensus on Helicobacter pylori. ARQUIVOS DE GASTROENTEROLOGIA 2013; 50:S0004-28032013005000113. [PMID: 23748591 DOI: 10.1590/s0004-28032013005000001] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2013] [Accepted: 02/14/2013] [Indexed: 12/11/2022]
Abstract
Signicant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.
Collapse
Affiliation(s)
- Luiz Gonzaga Coelho
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
| | | | | | | | | | | |
Collapse
|
|
32
|
Modified sequential therapy regimens for Helicobacter pylori eradication: a systematic review. Dig Liver Dis 2013; 45:18-22. [PMID: 23022424 DOI: 10.1016/j.dld.2012.08.025] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2012] [Revised: 08/23/2012] [Accepted: 08/29/2012] [Indexed: 02/08/2023]
Abstract
BACKGROUND Different modified sequential therapies have been proposed for Helicobacter pylori eradication. However, the efficacy of these regimens is controversial. METHODS We performed a systematic review of the literature and pooled-data analysis to assess: (a) the efficacy of different modified sequential therapies for H. pylori eradication, (b) the eradication rates achieved by these regimens as compared to either standard triple therapies or standard sequential regimen when available. RESULTS Overall 21 trials met inclusion criteria. The most used modified sequential therapy was the seven plus seven tetracycline-based regimen which achieved an overall 73.3% eradication rate (6 trials). Such therapy was more effective than the 14-day triple therapy (77.2% vs. 63.6%; 3 trials). The most used five plus five levofloxacin-based sequential therapy achieved a 95.8% and 90% cure rates when 250 mg and 500 mg levofloxacin twice daily were used, respectively. These success rates were higher as compared to that of either standard sequential or triple therapies. Other modified sequential therapies did not achieved acceptably high cure rates. Contradictory results emerged from 2 studies assessing the efficacy of a levofloxacin-based sequential regimen as a second-line therapy. CONCLUSIONS Both levofloxacin- and tetracycline-based sequential therapies have been proved to be more effective than standard triple therapies, confirming that the 'sequential' administration of drugs is a successful therapeutic procedure for H. pylori infection.
Collapse
|
|
33
|
Tay CY, Windsor HM, Thirriot F, Lu W, Conway C, Perkins TT, Marshall BJ. Helicobacter pylori eradication in Western Australia using novel quadruple therapy combinations. Aliment Pharmacol Ther 2012; 36:1076-83. [PMID: 23072648 DOI: 10.1111/apt.12089] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2012] [Revised: 06/05/2012] [Accepted: 09/26/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND Helicobacter pylori eradication rates with standard triple therapy are declining worldwide. The optimal management of H. pylori is evolving and new treatment combinations for antibiotic resistant H. pylori strains are required, especially for patients with penicillin allergy. AIM To review the effectiveness of alternative antibiotic combinations and necessity of pre-antibiotic sensitivity testing. METHODS A total of 310 consecutive patients who had failed at least one course of standard 7-day triple therapy initially prescribed by their physicians were included in this study between year 2007 and 2011. Antibiotics were prescribed based on pre-antibiotic sensitivity tests and, if any, patient's allergy to penicillin. RESULTS In 98.7% of the patients' samples, H. pylori was successfully cultured. The proportion resistant to clarithromycin and metronidazole was 94.1% and 67.6% respectively, with 65% resistant to both. For the in-house primary quadruple therapy, with Proton pump inhibitor, Amoxicillin, Rifabutin and Ciprofloxacin (PARC), H. pylori was successfully eradicated in 95.2% of patients. For patients allergic to amoxicillin, an alternative quadruple therapy using Proton pump inhibitor, Bismuth subcitrate, Rifabutin and Ciprofloxacin (PBRC) gave an eradication rate of 94.2%. Patients needing alternative salvage therapy were given novel personalised combinations consisting of bismuth, rifabutin, tetracycline or furazolidone; the eradication rate was 73.8%. CONCLUSIONS Patients who present with antibiotic resistant H. pylori can be confidently treated with PARC, PBRC or other personalised salvage therapies. These regimens can be used when treatment options are limited by penicillin allergy. Pre-treatment H. pylori antibiotic sensitivity tests contributed to the high eradication rate in this study.
Collapse
Affiliation(s)
- C Y Tay
- School of Pathology and Laboratory Medicine M502, University of Western Australia, Nedlands, WA, Australia.
| | | | | | | | | | | | | |
Collapse
|
|
34
|
Abstract
Helicobacter pylori resistance rates to antibiotics vary in different countries and even in different regions of the same country. Choice of treatment is strongly dependent on antibiotic resistance rates. In some countries, triple therapy with a proton-pump inhibitor, amoxicillin, and clarithromycin is still the best option, but eradication results fall short of what would be desired (90-95%) in countries with clarithromycin resistance >20%, bismuth-containing quadruple therapy, or nonbismuth sequential or concomitant therapies may then be the preferred option. Newer antibiotic regimens are awaited. Vaccination would be the best option, especially for developing countries, but little progress has been made in designing a vaccine.
Collapse
Affiliation(s)
- Bojan Tepes
- Department of Gastroenterology, Medical Centre Rogaska, Rogaska Slatina, Slovenia
| | | | | | | |
Collapse
|
|
35
|
Roesler BM, Costa SCB, Zeitune JMR. Eradication Treatment of Helicobacter pylori Infection: Its Importance and Possible Relationship in Preventing the Development of Gastric Cancer. ISRN GASTROENTEROLOGY 2012; 2012:935410. [PMID: 22778979 PMCID: PMC3384894 DOI: 10.5402/2012/935410] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/11/2012] [Accepted: 03/17/2012] [Indexed: 12/18/2022]
Abstract
Helicobacter pylori is the most important carcinogen for gastric adenocarcinoma. Bacterial virulence factors are essential players in modulating the immune response involved in the initiation of carcinogenesis in the stomach; host genetic factors contribute to the regulation of the inflammatory response and to the aggravation of mucosal damage. In terms of environmental factors, salt intake and smoking contribute to the development of lesions. Various therapeutic schemes are proposed to eradicate H. pylori infection, which could potentially prevent gastric cancer, offering the greatest benefit if performed before premalignant changes of the gastric mucosa have occurred.
Collapse
Affiliation(s)
- Bruna Maria Roesler
- Department of Clinical Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), 13.081-970 Campinas, SP, Brazil
- Center of Diagnosis of Digestive Diseases, Faculty of Medical Sciences, State University of Campinas (UNICAMP), 13.081-970 Campinas, SP, Brazil
| | - Sandra Cecília Botelho Costa
- Department of Clinical Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), 13.081-970 Campinas, SP, Brazil
| | - José Murilo Robilotta Zeitune
- Department of Clinical Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), 13.081-970 Campinas, SP, Brazil
- Center of Diagnosis of Digestive Diseases, Faculty of Medical Sciences, State University of Campinas (UNICAMP), 13.081-970 Campinas, SP, Brazil
| |
Collapse
|
|
36
|
Graham DY, Lu H. Furazolidone in Helicobacter pylori therapy: misunderstood and often unfairly maligned drug told in a story of French bread. Saudi J Gastroenterol 2012; 18:1-2. [PMID: 22249084 PMCID: PMC3271686 DOI: 10.4103/1319-3767.91724] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
- David Y. Graham
- Department of Medicine, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, TX USA and GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai, PR China. E-mail:
| | - Hong Lu
- Department of Medicine, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, TX USA and GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai, PR China. E-mail:
| |
Collapse
|