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Kouhsari E, Roshandel G, Hosseinzadeh S, Besharat S, Khori V, Amiriani T. Molecular Characterization of Antimicrobial Resistance and Virulence Genotyping among Helicobacter pylori-Positive Dyspeptic Patients in North Iran. Infect Disord Drug Targets 2025; 25:e090724231788. [PMID: 38984569 DOI: 10.2174/0118715265294927240617201332] [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: 12/30/2023] [Revised: 04/03/2024] [Accepted: 04/27/2024] [Indexed: 07/11/2024]
Abstract
BACKGROUND Iran has a relatively high prevalence of H. pylori, which correlates with high-risk areas for gastric cancer worldwide. METHODS Our study aimed to investigate the underlying genetic mechanisms associated with resistance to metronidazole (frxA, rdxA), clarithromycin (23S rRNA), tetracycline (16S rRNA), and fluoroquinolone (gyrA) in H. pylori-positive dyspeptic patients using PCR and sequencing. We further examined the potential correlation between resistance profiles and various virulence genotypes. RESULTS The rates of genetic mutations associated with resistance to metronidazole, fluoroquinolone, clarithromycin, and tetracycline were found to be 68%, 32.1%, 28.4%, and 11.1%, respectively. Well-documented multiple antibiotic resistance mutations were detected, such as rdxA and frxA (with missense and frameshift alterations), gyrA (Asp91, Asn87), 23S rRNA (A2142G, A2143G), and 16S rRNA (triple-base-pair substitutions AGA926-928→TTC). The cagA+ and vacA s1/m1 types were the predominant genotypes in our study. With the exception of metronidazole and tetracycline, no significant correlation was observed between the cagA+ and cagL+ genotypes and resistance-associated mutations. CONCLUSION The prevalence of antibiotic resistance-associated mutations in H. pylori was remarkably high in this region, particularly to metronidazole, ciprofloxacin, and clarithromycin. By conducting a simultaneous screening of virulence and resistance genotypes, clinicians can make informed decisions regarding the appropriate therapeutic regimen to prevent the escalation of antibiotic resistance against H. pylori infection in this specific geographical location.
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Affiliation(s)
- Ebrahim Kouhsari
- Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran
- Department of Laboratory Sciences, Faculty of Paramedicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Gholamreza Roshandel
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Sara Hosseinzadeh
- Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Sima Besharat
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Vahid Khori
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Taghi Amiriani
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
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Ou J, Li J, Liu Y, Su X, Li W, Zheng X, Zhang L, Chen J, Pan H. Quality appraisal of clinical guidelines for Helicobacter pylori infection and systematic analysis of the level of evidence for recommendations. PLoS One 2024; 19:e0301006. [PMID: 38598539 PMCID: PMC11006150 DOI: 10.1371/journal.pone.0301006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 03/09/2024] [Indexed: 04/12/2024] Open
Abstract
OBJECTIVES To systematically assess the quality of clinical practice guidelines (CPGs) for Helicobacter pylori (HP) infection and identify gaps that limit their development. STUDY DESIGN AND SETTING CPGs for HP infection were systematically collected from PubMed, Embase, the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, and six online guideline repositories. Three researchers independently used the AGREE Ⅱ tool to evaluate the methodological quality of the eligible CPGs. In addition, the reporting and recommendation qualities were appraised by using the RIGHT and AGREE-REX tools, respectively. The distribution of the level of evidence and strength of recommendation among evidence-based CPGs was determined. RESULTS A total of 7,019 records were identified, and 24 CPGs met the eligibility criteria. Of the eligible CPGs, 19 were evidence-based and 5 were consensus-based. The mean overall rating score of AGREE II was 50.7% (SD = 17.2%). Among six domains, the highest mean score was for scope and purpose (74.4%, SD = 17.7%) and the lowest mean score was for applicability (24.3%, SD = 8.9). Only three of 24 CPGs were high-quality. The mean overall score of recommendation quality was 35.5% (SD = 12.2%), and the mean scores in each domain of AGREE-REX and RIGHT were all ≤ 60%, with values and preferences scoring the lowest (16.6%, SD = 11.9%). A total of 505 recommendations were identified. Strong recommendations accounted for 64.1%, and only 34.3% of strong recommendations were based on high-quality evidence. CONCLUSION The overall quality of CPGs for HP infection is poor, and CPG developers tend to neglect some domains, resulting in a wide variability in the quality of the CPGs. Additionally, CPGs for HP infection lack sufficient high-quality evidence, and the grading of recommendation strength should be based on the quality of evidence. The CPGs for HP infection have much room for improvement and further researches are required to minimize the evidence gap.
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Affiliation(s)
- Jiayin Ou
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jiayu Li
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yang Liu
- The Second Clinical Medicine College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiaohong Su
- The People’s Hospital of Gaozhou, Gaozhou, China
| | - Wanchun Li
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiaojun Zheng
- Clinical Medical College of Acupuncture, Moxibustion, and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Lang Zhang
- The Second Clinical Medicine College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jing Chen
- School of Public Health and Management, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Huafeng Pan
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
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Temido MJ, Mbanze D, Almeida N, Oliveiros B, Gravito-Soares E, Figueiredo P. Is hybrid therapy more efficient in the eradication of Helicobacter pylori infection? A systematic review and meta-analysis. Ann Clin Microbiol Antimicrob 2023; 22:54. [PMID: 37403171 DOI: 10.1186/s12941-023-00582-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Accepted: 04/11/2023] [Indexed: 07/06/2023] Open
Abstract
INTRODUCTION Hybrid therapy (HT) is a non-bismuth quadruple therapy created to surpass Helicobacter pylori's (H. pylori) resistance rates to antibiotics. HT has excellent eradication rates, as well as a very good compliance and safety profile. We aim to compare HT with sequential therapy (ST) and concomitant therapy (CT) for the eradication of H. pylori. METHODS This systematic review was conducted following the principles of the PRISMA guidelines. Literature was electronically searched on the CENTRAL library, PubMed, Embase, Scopus, LILACS, and ClinicalTrials.gov. Only randomized controlled trials were included. The primary outcome evaluated was eradication rate of H. pylori. The secondary outcomes evaluated were adverse events and compliance rates. Meta-analyses were performed with Cochrane Review Manager 5.4. The Mantel-Haenszel method was used to estimate the pooled relative risk and 95% confidence interval of the eradication rates between HT and other regimens, as well as the secondary outcomes. RESULTS 10 studies were included, comprising 2993 patients. The mean eradication rates achieved by HT with intention-to-treat (ITT) and per-protocol (PP) analyses were, respectively, 86% (range: 79.2-90.8%) and 91.7% (range: 82.6-96.1%). No statistically significant difference was found in ITT eradication rate between HT and CT (relative risk: 1; 95% CI: 0.96- 1.03) and between HT and ST (relative risk: 1.02; 95% CI: 0.92-1.14). PP analysis revealed similar results. HT was associated with higher compliance rates than CT and slightly lower than ST. As far as adverse events are concerned, this meta-analysis demonstrated a higher occurrence of adverse events on the group of patients treated with CT when compared with HT. HT and ST showed similar results. CONCLUSION HT has similar eradication, compliance and adverse event rates when compared to ST, but a better safety profile than the CT.
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Affiliation(s)
- Maria José Temido
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3004-561, Coimbra, Portugal
| | - Dara Mbanze
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
- Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3004-561, Coimbra, Portugal
| | - Nuno Almeida
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3004-561, Coimbra, Portugal.
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
| | | | - Elisa Gravito-Soares
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3004-561, Coimbra, Portugal
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Pedro Figueiredo
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3004-561, Coimbra, Portugal
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
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Correia C, Almeida N, Leal C, Branquinho D, Fernandes A, Gravito-Soares E, Calhau C, Bastos I, Vasconcelos H, Figueiredo P. Single-capsule bismuth-based quadruple therapy as a rescue therapy for Helicobacter pylori eradication. Scand J Gastroenterol 2023; 58:227-231. [PMID: 36189844 DOI: 10.1080/00365521.2022.2119097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Helicobacter pylori (H. pylori) infection is highly prevalent in Portugal and its eradication is formally recommended. However, the indiscriminate use of antimicrobials has led to a drastic rise in antibiotic resistance, with the failure of traditional eradication schemes. A single-capsule bismuth-based quadruple therapy became recently available in Portugal. This study aims to evaluate the efficacy and safety of a bismuth-based quadruple therapy as a second-line or rescue therapy. PATIENTS AND METHODS This was a multicentric study. All consecutive patients that were treated with bismuth-based quadruple therapy, as second-line or salvage treatment between July 2017 and April 2019 were enrolled. Their medical records were reviewed and clinical and laboratorial parameters, as well as data on treatment efficacy and adverse events were retrieved. Patients were also contacted by phone after treatment to confirm compliance, adverse events, and global satisfaction with this specific therapy. RESULTS A total of 151 subjects were included (female-68.9%; mean age-56 ± 13.5 years). Patients were previously submitted to 212 eradication schemes (Median-1; 1-5; IQR:4): 33.5% triple clarithromycin-based, 25% sequential, 7.5% concomitant, 5.2% others, and in 28.8% it was not possible to know the previous eradication scheme(s) followed by the patient. The PPI of choice was esomeprazole (39.7%), followed by omeprazole (27.8%). Compliance was achieved in 93.4% and the overall eradication rate was 90.1% (95% CI: 84.6-94.2). Treatment-related adverse effects were experienced by 63 patients (41.7%; 95% CI: 34-49.7), being mild in 29, moderate in 19, and severe in 15. The main drawbacks of the treatment, from the patient's perspective, were the high price (47%) and the adverse effects (16.6%). Failure to eradicate H. pylori was correlated with the following: previous rifabutin-based scheme (0 vs. 100%; p = 0.010) and a higher number of previous treatment schemes (1.5 ± 0.7 vs. 2.3 ± 1.2; p < 0.001). CONCLUSION In this South-European country a single-capsule bismuth-based quadruple therapy is an excellent option as a second-line or rescue therapy, with acceptable compliance and side effects.
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Affiliation(s)
- Catarina Correia
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Nuno Almeida
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.,Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Carina Leal
- Gastroenterology Department, Leiria Hospital Centre, Leiria, Portugal
| | - Diogo Branquinho
- Gastroenterology Department, Baixo Vouga Hospital Centre, Aveiro, Portugal
| | | | - Elisa Gravito-Soares
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.,Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Carlos Calhau
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Isabel Bastos
- Gastroenterology Department, Baixo Vouga Hospital Centre, Aveiro, Portugal
| | | | - Pedro Figueiredo
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.,Faculty of Medicine, University of Coimbra, Coimbra, Portugal
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Ma Q, Li H, Liao J, Cai Z, Zhang B. Tailored therapy for Helicobacter pylori eradication: A systematic review and meta-analysis. Front Pharmacol 2022; 13:908202. [PMID: 36160444 PMCID: PMC9495299 DOI: 10.3389/fphar.2022.908202] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 08/22/2022] [Indexed: 11/13/2022] Open
Abstract
Background: Due to an increase in drug resistance, the eradication rate of H. pylori with empirical therapy has declined. Tailored therapy has been proposed as an alternative to standard empirical treatments. The necessity of personalized eradication therapy remains unclear. The aim of this study was to determine whether tailored therapy is superior to empirical therapy for H. pylori infection. Methods: We searched for eligible randomized controlled trials in the PubMed, Embase (Ovid), Wanfang, and Cochrane Central Register of Controlled Trials databases up to 10 December 2021. A random effects model comparing pooled relative risks (RRs) with 95% confidence intervals (CIs) was applied in the meta-analysis. Results: Twenty-one studies were included in the meta-analysis. In the first-line treatment, tailored therapy was more effective than empirical therapy (RR, 1.14 [95% CI, 1.08-1.21], I2 = 72.2%). In the second-line therapy setting, the results did not reveal significant differences between the two treatments (RR, 1.05 [95% CI, 0.84-1.30], I2 = 80.6%). A similar result was observed in mixed second- and third-line treatments (RR, 1.03 [95% CI, 0.96-1.11], I2 = 0.0%). Regarding adverse events, no significant differences were found between the two treatments (RR, 0.90 [95% CI, 0.80-1.01], I2 = 35.7%). Most of the results were highly heterogeneous. Conclusion: A tailored approach might provide a better eradication rate than empirical methods in first-line treatment. There might be no obvious advantage in second-line or mixed second- and third-line treatments third-line treatment. Due to the high heterogeneity, the results should be interpreted with caution. Further clinical studies are needed and justified.
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Affiliation(s)
- Qin Ma
- Division of Gastrointestinal Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Hancong Li
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Jing Liao
- Division of Gastrointestinal Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- West China School of Nursing, Sichuan University, Chengdu, China
| | - Zhaolun Cai
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Bo Zhang
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
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A Survey of Helicobacter pylori Antibiotic-Resistant Genotypes and Strain Lineages by Whole-Genome Sequencing in China. Antimicrob Agents Chemother 2022; 66:e0218821. [PMID: 35652644 PMCID: PMC9211431 DOI: 10.1128/aac.02188-21] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Antibiotic resistance is the most important factor leading to failed Helicobacter pylori eradication therapy, and personalized treatment based on antibiotic susceptibility is becoming increasingly important. To strengthen the understanding of antibiotic genotypic resistance of H. pylori and identify new antibiotic resistance loci, in this study, we identified phenotypic resistance information for 60 clinical isolates and compared the concordance of phenotypic and genotypic resistance using whole-genome sequencing (WGS). Clarithromycin and levofloxacin genotypic resistance was in almost perfect concordance with phenotypic resistance, with kappa coefficients of 0.867 and 0.833, respectively. All strains with the R16H/C mutation and truncation in rdxA were metronidazole resistant, with 100% specificity. For other genes of concern, at least one phenotypically sensitive strain had a previous mutation related to antibiotic resistance. Moreover, we found that the A1378G mutation of HP0399 and the A149G mutation of FabH might contribute to tetracycline resistance and multidrug resistance, respectively. Overall, the inference of resistance to clarithromycin and levofloxacin from genotypic resistance is reliable, and WGS has been very helpful in discovering novel H. pylori resistance loci. In addition, WGS has also enhanced our study of strain lineages, providing new ways to understand resistance information and mechanisms.
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Losurdo G, Giorgio F, Pricci M, Girardi B, Russo F, Riezzo G, Martulli M, Piazzolla M, Cocomazzi F, Abbruzzi F, Parente E, Paolillo R, Mileti A, Iannone A, Principi M, Ierardi E, Di Leo A. Helicobacter pylori Primary and Secondary Genotypic Resistance to Clarithromycin and Levofloxacin Detection in Stools: A 4-Year Scenario in Southern Italy. Antibiotics (Basel) 2020; 9:antibiotics9100723. [PMID: 33096925 PMCID: PMC7589162 DOI: 10.3390/antibiotics9100723] [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: 10/07/2020] [Revised: 10/16/2020] [Accepted: 10/19/2020] [Indexed: 02/07/2023] Open
Abstract
Antibiotic resistance has become an emerging problem for treating Helicobacter pylori (H. pylori) infection. Clarithromycin and levofloxacin are two key antibiotics used for its eradication. Therefore, we reviewed our experience with genotypic resistance analysis in stools to both clarithromycin and levofloxacin in the last four years to evaluate time trends, both in naive and failure patients. Patients collected a fecal sample using the THD fecal test device. Real-time polymerase chain reaction was performed to detect point mutations conferring resistance to clarithromycin (A2142C, A2142G, and A2143G in 23S rRNA) and levofloxacin (substitutions at amino acid position 87 and 91 of gyrA). One hundred and thirty-five naive patients were recruited between 2017-2020. Clarithromycin resistance was detected in 37 (27.4%). The time trend did not show any significant variation from 2017 to 2020 (p = 0.33). Primary levofloxacin resistance was found in 26 subjects (19.2%), and we observed a dramatic increase in rates from 2017 (10%) to 2018 (3.3%), 2019 (20%), and 2020 (37.8%). Ninety-one patients with at least one eradication failure were recruited. Secondary resistance to clarithromycin and levofloxacin was found in 59 (64.8%) and 45 patients (59.3%), respectively. In conclusion, our geographic area has a high risk of resistance to clarithromycin. There is also a progressive spreading of levofloxacin-resistant strains.
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Affiliation(s)
- Giuseppe Losurdo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (M.P.); (F.C.); (F.A.); (E.P.); (R.P.); (A.M.); (A.I.); (M.P.); (E.I.)
- Ph.D. Course in Organs and Tissues Transplantation and Cellular Therapies, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy
| | | | - Maria Pricci
- THD SpA, 42015 Correggio, Italy; (F.G.); (M.P.); (B.G.)
| | - Bruna Girardi
- THD SpA, 42015 Correggio, Italy; (F.G.); (M.P.); (B.G.)
| | - Francesco Russo
- Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology “S. de Bellis” Research Hospital, 70013 Castellana Grotte, Italy; (F.R.); (G.R.); (M.M.)
| | - Giuseppe Riezzo
- Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology “S. de Bellis” Research Hospital, 70013 Castellana Grotte, Italy; (F.R.); (G.R.); (M.M.)
| | - Manuela Martulli
- Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology “S. de Bellis” Research Hospital, 70013 Castellana Grotte, Italy; (F.R.); (G.R.); (M.M.)
| | - Mariano Piazzolla
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (M.P.); (F.C.); (F.A.); (E.P.); (R.P.); (A.M.); (A.I.); (M.P.); (E.I.)
| | - Francesco Cocomazzi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (M.P.); (F.C.); (F.A.); (E.P.); (R.P.); (A.M.); (A.I.); (M.P.); (E.I.)
| | - Francesco Abbruzzi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (M.P.); (F.C.); (F.A.); (E.P.); (R.P.); (A.M.); (A.I.); (M.P.); (E.I.)
| | - Elisabetta Parente
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (M.P.); (F.C.); (F.A.); (E.P.); (R.P.); (A.M.); (A.I.); (M.P.); (E.I.)
| | - Rosa Paolillo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (M.P.); (F.C.); (F.A.); (E.P.); (R.P.); (A.M.); (A.I.); (M.P.); (E.I.)
| | - Alessia Mileti
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (M.P.); (F.C.); (F.A.); (E.P.); (R.P.); (A.M.); (A.I.); (M.P.); (E.I.)
| | - Andrea Iannone
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (M.P.); (F.C.); (F.A.); (E.P.); (R.P.); (A.M.); (A.I.); (M.P.); (E.I.)
| | - Mariabeatrice Principi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (M.P.); (F.C.); (F.A.); (E.P.); (R.P.); (A.M.); (A.I.); (M.P.); (E.I.)
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (M.P.); (F.C.); (F.A.); (E.P.); (R.P.); (A.M.); (A.I.); (M.P.); (E.I.)
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (M.P.); (F.C.); (F.A.); (E.P.); (R.P.); (A.M.); (A.I.); (M.P.); (E.I.)
- Correspondence: ; Tel.: +39-80-559-2925
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Lin TF, Wu DC, Tsay FW, Tsai KW, Tsai TJ, Peng NJ, Kao SS, Chen WC, Chen YH, Hsu PI. Reverse hybrid therapy achieves a similar eradication rate as standard hybrid therapy for Helicobacter pylori infection. J Chin Med Assoc 2020; 83:233-237. [PMID: 31934941 DOI: 10.1097/jcma.0000000000000256] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Reverse hybrid therapy is a simplified hybrid treatment for Helicobacter pylori infection. It achieves a higher eradication rate than standard triple therapy. This study aimed to compare the efficacies of reverse hybrid and hybrid therapies in the treatment of H. pylori infection. METHODS From September 2008 to September 2017, 490 H. pylori-infected patients who received 14 days of reverse hybrid therapy (proton pump inhibitor plus amoxicillin for 14 days and clarithromycin plus metronidazole for the initial 7 days; n = 252) or hybrid therapy (proton pump inhibitor plus amoxicillin for 14 days and clarithromycin plus metronidazole for the final 7 days; n = 238) were included in this retrospective cohort study. Helicobacter pylori status was examined 6-8 weeks after therapy. RESULTS The eradication rates of the reverse hybrid and hybrid therapies by modified intention-to-treat analysis were comparable (96.4% vs 96.6%; p = 0.899). There were no differences in the efficacy of eradication between therapies for clarithromycin-resistant strains (87.0% vs 90.0%) or metronidazole-resistant strains (97.7% vs 100.0%). In addition, there were comparable frequencies of adverse events for both treatments (18.7% vs 13.0%) and treatment adherence (94.4% vs 97.1%). CONCLUSION Reverse hybrid therapy can achieve a similar eradication rate to hybrid therapy for H. pylori infection.
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Affiliation(s)
- Te-Fu Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Da Chien General Hospital, Miaoli, Taiwan, ROC
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Feng-Woei Tsay
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Kuo-Wang Tsai
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Tzung-Jiun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Nan-Jing Peng
- Department of Nuclear Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan, ROC
| | - Sung-Shuo Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Wen-Chi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Yan-Hua Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Ping-I Hsu
- Division of Gastroenterology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan, ROC
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Palmitessa V, Monno R, Panarese A, Cuppone R, Burattini O, Marangi S, Curlo M, Fumarola L, Petrosillo A, Parisi A, Capozzi L, Bianco A, Lippolis A. Evaluation of Antibiotic Resistance of Helicobacter pylori Strains Isolated in Bari, Southern Italy, in 2017-2018 by Phenotypic and Genotyping Methods. Microb Drug Resist 2020; 26:909-917. [PMID: 32101078 DOI: 10.1089/mdr.2019.0262] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objective: Helicobacter pylori antibiotic resistance is a constantly evolving process and local surveillance is warranted to guide clinicians in the choice of therapy. Materials and Methods: Antibiotic susceptibility testing was performed by E-test on 92 H. pylori strains, and resistance to clarithromycin and levofloxacin was also evaluated using a commercially available genotyping method. Results: In naïve patients the resistance to clarithromycin, levofloxacin, and metronidazole was 37.7%, 26.2%, and 16.4%, respectively, significantly lower than the percentage found in treated patients. Concomitant resistance to ≥2 antibiotics was also observed in naïve patients. The A2143G mutation of the 23S-rRNA gene was the most frequently detected, also in naïve patients. The highest minimum inhibitory concentration (MIC)50 value (256 mg/L) was associated with A2142 mutations in all the patients carrying them. For levofloxacin resistance a mutation in codon 87 was detected in 63.9% and in codon 91 in 36.1% of the H. pylori strains, without significant differences in the patients groups. A mutation in codon 87 was associated with the highest MIC50 value (32 mg/L). Conclusions: In our area, a high prevalence of H. pylori primary resistance was detected; these rates were higher in patients who had experienced failure of several courses of therapy. A better knowledge of the local epidemiology of resistance, and the genotypes responsible, will improve the H. pylori eradication rates.
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Affiliation(s)
- Valeria Palmitessa
- Laboratory of Microbiology and Virology, National Institute of Gastroenterology "Saverio de Bellis," Research Hospital, Bari, Italy
| | - Rosa Monno
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro," Bari, Italy
| | - Alba Panarese
- Department of Gastroenterology, National Institute of Gastroenterology "Saverio de Bellis," Research Hospital, Bari, Italy
| | - Renato Cuppone
- Department of Gastroenterology, National Institute of Gastroenterology "Saverio de Bellis," Research Hospital, Bari, Italy
| | - Osvaldo Burattini
- Department of Gastroenterology, National Institute of Gastroenterology "Saverio de Bellis," Research Hospital, Bari, Italy
| | - Stefania Marangi
- Department of Gastroenterology, National Institute of Gastroenterology "Saverio de Bellis," Research Hospital, Bari, Italy
| | - Margherita Curlo
- Department of Gastroenterology, National Institute of Gastroenterology "Saverio de Bellis," Research Hospital, Bari, Italy
| | - Luciana Fumarola
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro," Bari, Italy
| | - Antonella Petrosillo
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro," Bari, Italy
| | - Antonio Parisi
- Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata, Sezione di Putignano, Bari, Italy
| | - Loredana Capozzi
- Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata, Sezione di Putignano, Bari, Italy
| | - Angelica Bianco
- Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata, Sezione di Putignano, Bari, Italy
| | - Antonio Lippolis
- Laboratory of Microbiology and Virology, National Institute of Gastroenterology "Saverio de Bellis," Research Hospital, Bari, Italy
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10
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Kocsmár É, Kocsmár I, Buzás GM, Szirtes I, Wacha J, Takáts A, Hritz I, Schaff Z, Rugge M, Fassan M, Kiss A, Lotz G. Helicobacter pylori heteroresistance to clarithromycin in adults-New data by in situ detection and improved concept. Helicobacter 2020; 25:e12670. [PMID: 31701608 DOI: 10.1111/hel.12670] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2019] [Revised: 09/16/2019] [Accepted: 10/07/2019] [Indexed: 01/06/2023]
Abstract
BACKGROUND Clarithromycin (Cla) heteroresistance of Helicobacter pylori (H pylori) infections is commonly assessed by comparing the resistance status of antrum and corpus biopsy samples and by demonstrating the discrepancy between them (interniche heteroresistance). However, fluorescence in situ hybridization (FISH) technique is capable of showing the synchronous presence of susceptible and resistant bacteria (intraniche heteroresistance), enabling the detection of heteroresistant H pylori populations within one biopsy sample. MATERIALS AND METHODS Antrum and corpus biopsy specimens of 305 H pylori-infected patients were investigated with an rRNA-targeted Cla-resistance FISH test. Anamnestic data were collected from the institutional electronic register. Prevalence rates of susceptible, homo- and heteroresistant cases were correlated with the anamnestic and clinicopathological data. RESULTS Overall Cla-resistance rate was 23.9% (73 cases), consisting of 35 (11.5%) homoresistant and 38 (12.5%) heteroresistant cases. Thirty-five patients had at least one biopsy site where susceptible and resistant bacteria were present simultaneously. From this subset, 20 cases demonstrated intraniche heteroresistance on both sites. Prior Cla-based eradication attempts were more frequent in homoresistant than in susceptible and heteroresistant cases (P < .001, P < .001, respectively). Cla-containing therapy eradicated heteroresistant infections at a significantly lower rate in comparison with susceptible cases (P = .0112), but more effectively than homoresistants (P = .0393). CONCLUSIONS The most frequent type of Cla-heteroresistance is the coexistence of susceptible and resistant H pylori bacteria in the same location (intraniche heteroresistance). A previous Cla-based eradication attempt predisposes patients to homoresistant infection. Heteroresistance is characterized by a non-eradication-related background and intermediate characteristics in many respects when compared to susceptible and homoresistant cases.
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Affiliation(s)
- Éva Kocsmár
- Second Department of Pathology, Semmelweis University, Budapest, Hungary
| | - Ildikó Kocsmár
- Second Department of Pathology, Semmelweis University, Budapest, Hungary
| | - György Miklós Buzás
- Department of Gastroenterology, Ferencváros Health Centre, Budapest, Hungary
| | - Ildikó Szirtes
- Second Department of Pathology, Semmelweis University, Budapest, Hungary
| | - Judit Wacha
- First Department of Surgery, Semmelweis University, Budapest, Hungary
| | - Alajos Takáts
- First Department of Surgery, Semmelweis University, Budapest, Hungary
| | - István Hritz
- First Department of Surgery, Semmelweis University, Budapest, Hungary
| | - Zsuzsa Schaff
- Second Department of Pathology, Semmelweis University, Budapest, Hungary
| | - Massimo Rugge
- Surgical Pathology & Cytopathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy.,Veneto Tumor Registry (RTV), Veneto Regional Authority, Padova, Italy
| | - Matteo Fassan
- Surgical Pathology & Cytopathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - András Kiss
- Second Department of Pathology, Semmelweis University, Budapest, Hungary
| | - Gábor Lotz
- Second Department of Pathology, Semmelweis University, Budapest, Hungary
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11
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High Prevalence of Antibiotic Resistance in Iranian Helicobacter pylori Isolates: Importance of Functional and Mutational Analysis of Resistance Genes and Virulence Genotyping. J Clin Med 2019; 8:jcm8112004. [PMID: 31744181 PMCID: PMC6912791 DOI: 10.3390/jcm8112004] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 11/11/2019] [Accepted: 11/14/2019] [Indexed: 12/14/2022] Open
Abstract
The high prevalence of antibiotic resistance in Helicobacter pylori has become a great challenge in Iran. The genetic mutations that contribute to the resistance have yet to be precisely identified. This study aimed to investigate the prevalence of antibiotic resistance and virulence markers in Iranian H. pylori isolates and to analyze if there is any association between resistance and genotype. Antibiotic susceptibility patterns of 68 H. pylori isolates were investigated against metronidazole, clarithromycin, amoxicillin, rifampicin, ciprofloxacin, levofloxacin, and tetracycline by the agar dilution method. The frxA, rdxA, gyrA, gyrB, and 23S rRNA genes of the isolates were sequenced. The virulence genotypes were also determined using PCR. Metronidazole resistance was present in 82.4% of the isolates, followed by clarithromycin (33.8%), ciprofloxacin (33.8%), rifampicin (32.4%), amoxicillin (30.9%), levofloxacin (27.9%), and tetracycline (4.4%). Overall, 75% of the isolates were resistant to at least two antibiotics tested and considered as a multidrug resistance (MDR) phenotype. Most of the metronidazole-resistant isolates carried frameshift mutations in both frxA and rdxA genes, and premature termination occurred in positions Q5Stop and Q50Stop, respectively. Amino acid substitutions M191I, G208E, and V199A were predominantly found in gyrA gene of fluoroquinolone-resistant isolates. A2143G and C2195T mutations of 23S rRNA were found in four clarithromycin-resistant isolates. Interestingly, significant associations were found between resistance to metronidazole (MNZ) and cagA-, sabA-, and dupA-positive genotypes, with p = 0.0002, p = 0.0001, and p = 0.0001, respectively. Furthermore, a significant association was found between oipA “on” status and resistance to amoxicillin (AMX) (p = 0.02). The prevalence of H. pylori antibiotic resistance is high in our region, particularly that of metronidazole, clarithromycin, ciprofloxacin, and MDR. Simultaneous screening of virulence and resistance genotypes can help clinicians to choose the appropriate therapeutic regime against H. pylori infection.
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12
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Kouitcheu Mabeku LB, Eyoum Bille B, Tepap Zemnou C, Tali Nguefack LD, Leundji H. Broad spectrum resistance in Helicobacter pylori isolated from gastric biopsies of patients with dyspepsia in Cameroon and efflux-mediated multiresistance detection in MDR isolates. BMC Infect Dis 2019; 19:880. [PMID: 31640588 PMCID: PMC6806547 DOI: 10.1186/s12879-019-4536-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 10/09/2019] [Indexed: 12/17/2022] Open
Abstract
Background Antibiotic resistance is a leading cause of treatment failure in Helicobacter pylori infection. In Africa, there are very little data concerning the susceptibility of Helicobacter pylori isolates to antibiotics. The purpose of this study was to evaluate the resistance prevalence of Helicobacter pylori strains circulating in Cameroon, and to assess overexpression of efflux pump as a possible multi-drug resistance mechanisms. Methods A total of 140 H. pylori isolates were recovered from gastric biopsies of dyspeptic patients in two reference hospitals in Cameroon and analyzed for their antimicrobial susceptibility to amoxicillin, co-amoxiclav, ampicillin, penicillin, imipenem, metronidazole, rifabutin, erythromycin, clarithromycin, azithromycin, levofloxacin, ciprofloxacin, norfloxacin, tetracycline, doxycycline and minocycline. Antibiotic sensitivity was tested by disk diffusion method. Phe-Arg-naphthylamide (PAßN) was used as efflux pump inhibitor. INT broth microdilution method in supplemented Brain Heart Infusion broth was used to determine the MIC of ampicillin, amoxicillin, metronidazole, erythromycin, clarithromycin and doxycycline in the absence and the presence of PAßN against 32 selected MDR isolates. Results Overall H. pylori resistance rate was 100% to ampicillin, penicillin and co-amoxiclav; 97.14% to amoxicillin, 97.85% to metronidazole, 47.85% to erythromycin, 13.57% to clarithromycin; 5, 2.86 and 0.71% to doxycycline, tetracycline and minocycline respectively. No resistance to azithromycin, rifabutin, imipenem, ciprofloxacin, norfloxacin and levofloxacin was detected among H. pylori isolates. Seventy percent (70%) of the tested isolates elicited a multiple drugs resistance pattern; 42.57% double, 15.71% triple and 5.71% quadruple drugs resistance. Metronidazole and amoxicillin were more concerned with double resistance pattern (86.76%). The spectrum of activity recorded with metronidazole, doxycycline, clarithromycin and erythromycin ranged from 0 to 100% in the absence to the presence of PAßN against the tested MDR isolates. An 8 to 128-fold increase in potency was also noticed with these antibiotics in the presence of PAßN. Conclusion With regard to the high resistance rate to both amoxicillin and metronidazole, these drugs should be avoided as components of triple therapy in our milieu. In contrast, ciprofloxacin, norfloxacin, levofloxacin and tetracyclines could be used to achieve a better eradication rate and to reduce the risk of selection of H. pylori resistant strains.
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Affiliation(s)
- Laure Brigitte Kouitcheu Mabeku
- Microbiology and Pharmacology Laboratory, Department of Biochemistry, Faculty of Science, University of Dschang, P. O. Box, 67, Dschang, Cameroon.
| | - Bertrand Eyoum Bille
- Microbiology and Pharmacology Laboratory, Department of Biochemistry, Faculty of Science, University of Dschang, P. O. Box, 67, Dschang, Cameroon
| | - Cromwell Tepap Zemnou
- Microbiology and Pharmacology Laboratory, Department of Biochemistry, Faculty of Science, University of Dschang, P. O. Box, 67, Dschang, Cameroon
| | - Lionel Danny Tali Nguefack
- Microbiology and Pharmacology Laboratory, Department of Biochemistry, Faculty of Science, University of Dschang, P. O. Box, 67, Dschang, Cameroon
| | - Hubert Leundji
- Gastroenterology Department, Laquintinie Hospital of Douala, P. O. Box, 4035, Douala, Cameroon
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13
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Chang YW, Ko WJ, Oh CH, Park YM, Oh SJ, Moon JR, Cho JH, Kim JW, Jang JY. Clarithromycin resistance and female gender affect Helicobacter pylori eradication failure in chronic gastritis. Korean J Intern Med 2019; 34:1022-1029. [PMID: 29898576 PMCID: PMC6718756 DOI: 10.3904/kjim.2018.054] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 03/09/2018] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND/AIMS The eradication rate of the first-line triple therapy (a proton pump inhibitor, clarithromycin, and amoxicillin) for Helicobacter pylori infection has gradually decreased in Korea. We evaluated whether clinical parameters, clarithromycin resistance, and CYP2C19 genotype can affect the eradication failure. METHODS A total of 203 patients with H. pylori-positive chronic gastritis were consecutively enrolled. They received clarithromycin-based triple therapy for 7 days. A clarithromycin resistance test was performed by detection of A2142G and A2143G point mutations in H. pylori 23S rRNA. The CYP2C19 genotype was examined for polymorphism G681A of exon 5 and G636A of exon 4 by polymerase chain reaction with restriction fragment length polymorphism. Eradication was assessed by a 13C-urea breath test 4 weeks after treatment. RESULTS Of 203 patients, 190 completed the study. The eradication rate was 64.0% according to intention-to-treat analysis and 68.4% by per-protocol analysis. CY-P2C19 genotypes were identified as follows: 75 poor metabolizers, 75 intermediate metabolizers, and 40 rapid metabolizers. Nonetheless, this polymorphism was not significantly associated with eradication failure (p = 0.682). Clarithromycin resistance was detected in 33/190 patients (17.4%), and their eradication rate was zero. Clarithromycin resistance (odds ratio [OR], 19.13; 95% confidence interval [CI], 9.35 to 35.09) and female gender (OR, 1.73; 95% CI, 1.15 to 4.25) were significantly associated with eradication failure. The other clinical parameters such as age, cigarette smoking, alcohol intake, the body mass index, hypertension, and diabetes were not significantly associated with eradication. CONCLUSION Clarithromycin resistance and female gender are factors affecting H. pylori eradication failure in patients with chronic gastritis.
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Affiliation(s)
- Young Woon Chang
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Weon Jin Ko
- Department of Internal Medicine, CHA Gumi Medical Center, CHA University School of Medicine, Gumi, Korea
| | - Chi Hyuk Oh
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
- Correspondence to Chi Hyuk Oh, M.D. Division of Gastroenterology and Hepatology, Department of Internal medicine, Kyung Hee University School of Medicine, 23 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea Tel: +82-2-958-8114 Fax: +82-2-958-8147 E-mail:
| | - Yoo Min Park
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Shin Ju Oh
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jung Rock Moon
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jun-Hyung Cho
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Jung-Wook Kim
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jae-Young Jang
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
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14
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Jung DH, Kim JH, Jeong SJ, Park SY, Kang IM, Lee KH, Song YG. Peptide Nucleic Acid Probe-Based Analysis as a New Detection Method for Clarithromycin Resistance in Helicobacter pylori. Gut Liver 2018; 12:641-647. [PMID: 30037168 PMCID: PMC6254629 DOI: 10.5009/gnl18111] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Revised: 05/17/2018] [Accepted: 06/10/2018] [Indexed: 12/17/2022] Open
Abstract
Background/Aims Helicobacter pylori eradication rates are decreasing because of increases in clarithromycin resistance. Thus, finding an easy and accurate method of detecting clarithromycin resistance is important. Methods We evaluated 70 H. pylori isolates from Korean patients. Dual-labeled peptide nucleic acid (PNA) probes were designed to detect resistance associated with point mutations in 23S ribosomal ribonucleic acid gene domain V (A2142G, A2143G, and T2182C). Data were analyzed by probe-based fluorescence melting curve analysis based on probe-target dissociation temperatures and compared with Sanger sequencing. Results Among 70 H. pylori isolates, 0, 16, and 58 isolates contained A2142G, A2143G, and T2182C mutations, respectively. PNA probe-based analysis exhibited 100.0% positive predictive values for A2142G and A2143G and a 98.3% positive predictive value for T2182C. PNA probe-based analysis results correlated with 98.6% of Sanger sequencing results (κ-value=0.990; standard error, 0.010). Conclusions H. pylori clarithromycin resistance can be easily and accurately assessed by dual-labeled PNA probe-based melting curve analysis if probes are used based on the appropriate resistance-related mutations. This method is fast, simple, accurate, and adaptable for clinical samples. It may help clinicians choose a precise eradication regimen.
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Affiliation(s)
- Da Hyun Jung
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul,
Korea
| | - Jie-Hyun Kim
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul,
Korea
| | - Su Jin Jeong
- Division of Infectious Diseases, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul,
Korea
| | - Soon Young Park
- Division of Infectious Diseases, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul,
Korea
| | - Il-Mo Kang
- Korea Institute of Geoscience and Mineral Resources, Daejeon,
Korea
| | - Kyoung Hwa Lee
- Division of Infectious Diseases, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul,
Korea
| | - Young Goo Song
- Division of Infectious Diseases, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul,
Korea
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15
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Berberine Combined with Triple Therapy versus Triple Therapy for Helicobacter pylori Eradication: A Meta-Analysis of Randomized Controlled Trials. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:8716910. [PMID: 30410559 PMCID: PMC6207132 DOI: 10.1155/2018/8716910] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Revised: 06/18/2018] [Accepted: 07/19/2018] [Indexed: 12/30/2022]
Abstract
Objective To assess the effects and safety of berberine combined with triple therapy on Helicobacter pylori (H. pylori) eradication in adults. Methods PubMed, MEDLINE, EMBASE, Cochrane Library, and Chinese databases including China National Knowledge Infrastructure (CNKI), Wanfang data, Chinese Technology Journal Full-text Database (VIP), and China biomedical literature database (CBM) were searched to obtain the eligible studies published up to October 10, 2017. The primary outcome was eradication rate of H. pylori. The secondary outcome was incidence of adverse effects. Data analysis was conducted by RevMan5.2 and Stata V.9.0 software. Trial sequential analysis (TSA) was performed to assess the risk of random error and the validity of conclusion with TSA program version 0.9 beta. Results The meta-analysis results indicated berberine combined with triple therapy could improve the eradication rates of H. pylori (urea breath test subgroup: RR=1.18, 95%CI=(1.12,1.24), P < 0.00001, biopsy subgroup: RR=1.23, 95%CI=(1.13,1.34), P < 0.00001) and reduce the total occurrence of adverse effects (OR=0.59, 95%CI(0.46, 0.75), P < 0.0001) when compared with only using triple therapy. Besides, the incidence of nausea (OR=0.59, 95%CI(0.41, 0.86), P < 0.05) and diarrhea (OR=0.41, 95%CI(0.24, 0.71) was remarkably lower in experimental group while that of abdominal distention (OR=0.64, 95%CI(0.40,1.04), P > 0.05) and vomiting (OR=0.65, 95%CI(0.37, 1.15), P > 0.05) had no significant change. TSA of H. pylori eradication rates and adverse effects incidence illustrated that the cumulative value of Z-curve went across the conventional boundary value, trial sequential monitoring boundary for benefit, and required information size, suggesting the results were stable. Conclusion Evidence from meta-analysis suggested that berberine combined with triple therapy can be an option for increasing H. pylori eradication rates and reducing overall therapy-related adverse effects incidence, particularly nausea and diarrhea, whereas more randomized controlled trials designed according to CONSORT statement are demanded to support the efficacy in further studies.
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16
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Kwon S, Lee DH, Kang JB, Kim N, Park YS, Shin CM, Yoon H, Choi YJ. [The Efficacy of Bismuth-containing Quadruple Therapy after Moxifloxacin-based Sequential Therapy Failure in Helicobacter pylori Eradication]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2018; 71:196-203. [PMID: 29684968 DOI: 10.4166/kjg.2018.71.4.196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Background/Aims Moxifloxacin-based sequential therapy showed an excellent eradication rate as the first line treatment of Helicobacter pylori (H. pylori) infection. However, to the best of our knowledge, there were only a few studies on the treatment of those with failed moxifloxacin-based sequential therapy. Hence, this study was to investigate the efficacy of bismuth-containing quadruple therapy in those with failed moxifloxacin-based sequential or reverse sequential therapy for H. pylori eradication. Methods Between January 2013 and March 2016, we retrospectively analyzed patients who failed to eradicate H. pylori using moxifloxacin-based sequential (rabeprazole 20 mg bid and amoxicillin 1 g bid for 5-7 days, followed by rabeprazole 20 mg bid, metronidazole 500 mg bid, and moxifloxacin 400 mg qd for 5-7 days) and 10 days moxifloxacin-based reverse sequential therapy as the first line treatment. Then we investigated the eradication rates of bismuth-containing quadruple therapy as the second line treatment. All subjects had no history of H. pylori eradication before. Eradication rates were described as intention-to-treat (ITT) and per-protocol (PP) analyses. H. pylori status was evaluated by ¹³C-urea breath test 6 weeks after the end of the treatment. Moreover, we examined any side effects that caused discontinuation of therapy. Results Twenty-three patients received bismuth-containing quadruple therapy as the second line treatment. The overall eradication rates by ITT and PP analyses were 60.87% (n=14/23) and 73.68% (n=14/19). All the patients showed good compliance, and there were no serious adverse events. Conclusions Bismuth-containing quadruple therapy is insufficient as the second line eradication treatment after a failed attempt of moxifloxacin-based sequential or reverse sequential therapy. Large-scale clinical trials should be performed to establish better clinical evidence.
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Affiliation(s)
- Soohoon Kwon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Bin Kang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yoon Jin Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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17
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Tursi A, Franceschi M, Allegretta L, Savarino E, De Bastiani R, Elisei W, Baldassarre G, Ferronato A, Scida S, Miraglia C, Penna A, Licci C, Rizzo GL, Pranzo G, Cassieri C, Brandimarte G, Picchio M, Di Mario F. Effectiveness and Safety of Pylera® in Patients Infected by Helicobacter Pylori: A Multicenter, Retrospective, Real Life Study. Dig Dis 2018; 36:264-268. [PMID: 29669354 DOI: 10.1159/000487391] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Accepted: 01/30/2018] [Indexed: 02/02/2023]
Abstract
BACKGROUND Our aims were to assess the real life effectiveness and safety of the new bismuth-containing quadruple therapy in a large population of patients infected by Helicobacter pylori. METHODS Consecutive dyspeptic H. pylori-positive patients were enrolled, both naïve for treatment and already unsuccessfully treated. Patients were treated with Pylera® 3 capsules 4 times/daily plus omeprazole 20 mg or esomeprazole 40 mg 2 times/daily for 10 days. Eradication was confirmed using a urea-breath test (at least 30 days after the end of the treatment). Efficacy and safety were assessed. RESULTS A total of 349 patients were treated. H. pylori eradication was achieved in 316 (90.5%, 95% CIs 80.8-1.0) patients in the intention-to-treat population, and in 93.5% (95% CIs 83.5-1.0) in the per-protocol population. No difference in the eradication rate was found between naïve and previously treated patients (91.3 vs. 90.0%, p = 0.901). Adverse events occurred in 55 patients (15.8%, 95% CIs 11.9-20.1). Five patients discontinued treatment: 2 patients suffered from severe abdominal pain, one patient from headache, one patient from diarrhea, and one patient from diffuse urticarial rush. CONCLUSIONS Pylera® achieved a remarkable eradication rate in real life both as first treatment and as a rescue therapy, with a good safety profile.
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Affiliation(s)
| | | | - Leonardo Allegretta
- Division of Gastroenterology, "S. Caterina Novella" Hospital, Galatina, Italy
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Rudi De Bastiani
- Italian Association for Gastroenterology in Primary Care (GICA-CP), Feltre, Italy
| | | | | | | | - Serena Scida
- Department of Clinical and Experimental Medicine, Gastroenterology Unit, University of Parma, Parma, Italy
| | - Chiara Miraglia
- Department of Clinical and Experimental Medicine, Gastroenterology Unit, University of Parma, Parma, Italy
| | - Antonio Penna
- Division of Gastroenterology, "S. Paolo" Hospital, Bari, Italy
| | - Claudio Licci
- Private Practice Gastroenterologist, Monopoly, Italy
| | | | - Giuseppe Pranzo
- Digestive Endoscopy Service, "Valle d'Itria" Hospital, Martina Franca, Italy
| | - Claudio Cassieri
- Division of Internal Medicine and Gastroenterology, "Cristo Re" Hospital, Rome, Italy
| | - Giovanni Brandimarte
- Division of Internal Medicine and Gastroenterology, "Cristo Re" Hospital, Rome, Italy
| | | | - Francesco Di Mario
- Department of Clinical and Experimental Medicine, Gastroenterology Unit, University of Parma, Parma, Italy
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De Francesco V, Pontone S, Bellesia A, Serviddio G, Panetta C, Palma R, Zullo A. Quadruple, sequential, and concomitant first-line therapies for H. pylori eradication: a prospective, randomized study. Dig Liver Dis 2018; 50:139-141. [PMID: 29089267 DOI: 10.1016/j.dld.2017.10.009] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Revised: 09/06/2017] [Accepted: 10/10/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Current Italian guidelines recommend 10-day bismuth-based or bismuth-free (sequential and concomitant) regimens for first-line H. pylori eradication. However, comparison among these regimens is lacking in our country. AIM To perform a 'head-to-head' comparison among these three therapies as first-line treatment for H. pylori eradication in clinical practice. METHODS This was a prospective, open-label randomized study enrolling consecutive patients diagnosed with H. pylori infection never previously treated. Patients were randomized to receive one of the following 10-day therapies: (a) Bismuth-based therapy: esomeprazole 20mg b.i.d and Pylera 3 tablets q.i.d; (b) Concomitant therapy: esomeprazole 20mg plus amoxicyllin 1,000mg, clarithromycin 500mg and tinidazole 500mg (all b.i.d.), and (c) Sequential therapy: esomeprazole 20mg plus amoxicyllin 1,000mg for 5days followed by esomeprazole 20mg plus clarithromycin 500mg and tinidazole 500mg for 5days (all b.i.d). H. pylori eradication was assessed by using UBT 4-6 weeks after the end of therapy. RESULTS Overall, 187 patients were enrolled. The eradication rates achieved with Pylera, concomitant and sequential were 85.2%, 95.2%, and 93.6%, respectively, at intention to treat, and 94.5%, 96.7%, and 95.1% at per protocol analyses, without a statistically significant difference. The incidence of severe side-effects was higher with the bismuth-based therapy than with the two bismuth-free regimens (9.8% vs 1.6%; p=0.046). CONCLUSIONS Bismuth-based and bismuth-free therapies are equally effective for first-line H. pylori eradication. However, bismuth therapy was more frequently interrupted for side-effects than bismuth-free therapies.
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Affiliation(s)
- Vincenzo De Francesco
- Section of Gastroenterology and Department of Medical Sciences, University of Foggia, Foggia, Italy.
| | - Stefano Pontone
- Department of Surgical Sciences, "Sapienza" University of Rome, Italy
| | - Annamaria Bellesia
- Section of Gastroenterology and Department of Medical Sciences, University of Foggia, Foggia, Italy
| | - Gaetano Serviddio
- Cure University Centre for Liver Disease Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Italy
| | - Cristina Panetta
- Department of Surgical Sciences, "Sapienza" University of Rome, Italy
| | - Rossella Palma
- Department of Surgical Sciences, "Sapienza" University of Rome, Italy
| | - Angelo Zullo
- Gastroenterology,'Nuovo Regina Margherita' Hospital, Rome, Italy
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A Randomized Controlled Trial Shows that both 14-Day Hybrid and Bismuth Quadruple Therapies Cure Most Patients with Helicobacter pylori Infection in Populations with Moderate Antibiotic Resistance. Antimicrob Agents Chemother 2017; 61:AAC.00140-17. [PMID: 28807915 DOI: 10.1128/aac.00140-17] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Accepted: 08/01/2017] [Indexed: 12/14/2022] Open
Abstract
Hybrid therapy is a novel two-step treatment achieving a high eradication rate for Helicobacter pylori infection. Currently, whether this new therapy achieves a higher eradication rate than bismuth quadruple therapy remains an unanswered question. The aim of this prospective, randomized comparative study was to investigate the efficacies of 14-day hybrid therapy and bismuth quadruple therapy in the treatment of H. pylori infection. From July 2013 to June 2015, eligible H. pylori-infected subjects were randomly assigned to receive either 14-day bismuth quadruple therapy (pantoprazole, bismuth subcitrate, tetracycline, and metronidazole for 14 days) or 14-day hybrid therapy (a 7-day dual therapy with pantoprazole plus amoxicillin, followed by a 7-day quadruple therapy with pantoprazole plus amoxicillin, clarithromycin, and metronidazole). H. pylori status was examined 6 weeks after the end of treatment. Three hundred thirty H. pylori-infected participants were randomized to receive 14-day bismuth quadruple therapy (n = 164) or 14-day hybrid therapy (n = 166). The eradication rates by intention-to-treat analysis were similar: 93.9% versus 92.8%, respectively (95% confidence interval [CI], -4.3% to 5.4%; P = 0.68). Per-protocol analysis yielded similar results (96.7% versus 94.9%, respectively; P = 0.44). However, bismuth quadruple therapy had a higher frequency of adverse events than hybrid therapy (55.5% versus 15.7%, respectively; 95% CI, 30.4% to 49.2%; P < 0.001). The two treatments exhibited comparable drug adherence (93.9% versus 97%, respectively). The resistance rates of antibiotics were: clarithromycin, 16.7% of patients; amoxicillin, 1.3%; metronidazole, 25%; and tetracycline, 0%. In the bismuth quadruple therapy group, the eradication rate of metronidazole-resistant strains was lower than that of metronidazole-susceptible strains (70.0% versus 96.4%, respectively; P = 0.04). In the hybrid therapy group, no significant impact of clarithromycin or metronidazole resistance on eradication rates was identified. Both 14-day hybrid and bismuth quadruple therapies cure most patients with H. pylori infection in populations with moderate antibiotic resistance. However, the 14-day hybrid therapy has fewer adverse effects than the bismuth quadruple therapy. (This study has been registered at ClinicalTrials.gov under identifier NCT02541864.).
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Kwon S, Lee DH, Kang JB, Kim N, Park YS, Shin CM, Yoon H, Choi YJ. [The Efficacy of Moxifloxacin-containing Triple Therapy after Hybrid Therapy Failure in Helicobacter pylori Eradication]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2017; 70:72-80. [PMID: 28830132 DOI: 10.4166/kjg.2017.70.2.72] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Background/Aims Hybrid therapy was successful in eradicating Helicobacter pylori (H. pylori) according to previous reports. However, to the best of our knowledge, there have only been a few studies evaluating the optimal choice after hybrid failure. Hence, we aimed to evaluate the efficacy of moxifloxacin-containing triple therapy after hybrid therapy failure in H. pylori eradication. Methods Between January 2013 and March 2016, we retrospectively reviewed patients who underwent failed hybrid therapy, as first line treatment, in eradicating H. pylori (rabeprazole and amoxicillin b.i.d for 14 days, in addition to clarithromycin and metronidazole b.i.d for final 7 days). Then, we investigated the eradication rates of moxifloxacin-containing triple therapy (rabeprazole, amoxicillin b.i.d and moxifloxacin qd) as the second line of treatment. Intention-to-treat (ITT) and per-protocol (PP) analyses were used to determine the eradication rate. We evaluated the status of H. pylori by using 13C-urea breath test 6 weeks after the final treatment. Moreover, compliance and adverse effects of each patient were analyzed. Results Among those who failed the initial hybrid therapy, 11 patients received moxifloxacin-containing triple therapy. The overall eradication rates, as determined by ITT and PP, were 72.7% (n=8/11) and 80% (n=8/10), respectively. The compliance rate was 100%, and there were no serious adverse effects. Conclusions Moxifloxacin-containing triple therapy can be used as a second line therapy in case of hybrid therapy failure. A large scale study is necessary to confirm the findings of this study and establish clinical evidence.
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Affiliation(s)
- Soohoon Kwon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Bin Kang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yoon Jin Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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Tursi A, Di Mario F, Franceschi M, De Bastiani R, Elisei W, Baldassarre G, Ferronato A, Grillo S, Landi S, Zamparella M, De Polo M, Boscariolo L, Picchio M. New bismuth-containing quadruple therapy in patients infected with Helicobacter pylori: A first Italian experience in clinical practice. Helicobacter 2017; 22. [PMID: 28125857 DOI: 10.1111/hel.12371] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Rising antibiotic resistance requires the evaluation of new and effective therapies. AIMS To test the efficacy and safety of the new bismuth-containing quadruple therapy in patients infected with Helicobacter pylori. MATERIAL AND METHODS Consecutive H. pylori-positive dyspeptic patients were enrolled, either naïve or with previous failure treatment. Patients were treated with Pylera® (three-in-one capsules containing bismuth subcitrate potassium 140 mg, metronidazole 125 mg, and tetracycline 125 mg) three capsules q.i.d. plus omeprazole 20 mg or esomeprazole 40 mg b.i.d. for 10 days. Eradication was confirmed using an urea breath test (at least 30 days after the end of treatment). Efficacy was assessed by UBT and safety by means of treatment-emergent adverse events. RESULTS One hundred and thirty-one patients were included in the study: 42% of patients were naïve, and 58%, with previous failure treatment. H. pylori eradication was achieved in 124 patients (94.7%, 95% confidence intervals (CIs) 89.3-97.8) in ITT population. In the PP population, the percentage was 97.6% (95%, CIs 93.3-99.2). No difference in eradication rate was found either between naïve and previously treated patients (92.7% vs 96.0%, P=.383), or smoking and nonsmoking ones, or in patients taking omeprazole or esomeprazole. Treatment-emergent adverse events occurred in 35 patients (26.7%, 95% CIs 19.9-34.9). They were mild in all cases except in four, who discontinued the study due to diarrhea (three patients) and diffuse urticarial rush (one patient). CONCLUSIONS Pylera® achieved a remarkable eradication rate in clinical practice, irrespective if it was used as first treatment or as a rescue therapy. Treatment-emergent adverse events were uncommon generally mild.
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Affiliation(s)
- Antonio Tursi
- Gastroenterology Service, ASL BAT, Andria (BT), Italy
| | - Francesco Di Mario
- Department of Clinical & Experimental Medicine, Gastroenterology Unit, University of Parma, Parma, Italy
| | | | - Rudi De Bastiani
- Italian Association for Gastroenterology in Primary Care (GICA-CP), Feltre (BL), Italy
| | - Walter Elisei
- Division of Gastroenterology, ASL RM6, Albano Laziale (Roma), Italy
| | | | - Antonio Ferronato
- Digestive Endoscopy Unit, ULSS4 Alto Vicentino, Santorso, Schio (VI), Italy
| | - Simone Grillo
- Department of Clinical & Experimental Medicine, Gastroenterology Unit, University of Parma, Parma, Italy
| | - Stefano Landi
- Department of Clinical & Experimental Medicine, Gastroenterology Unit, University of Parma, Parma, Italy
| | - Maria Zamparella
- Italian Association for Gastroenterology in Primary Care (GICA-CP), Feltre (BL), Italy
| | - Manuela De Polo
- Italian Association for Gastroenterology in Primary Care (GICA-CP), Feltre (BL), Italy
| | - Laura Boscariolo
- Italian Association for Gastroenterology in Primary Care (GICA-CP), Feltre (BL), Italy
| | - Marcello Picchio
- Division of Surgery, "P. Colombo" Hospital, ASL RM6, Velletri (Rome), Italy
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Gunnarsdottir AI, Gudjonsson H, Hardardottir H, Jonsdottir KD, Bjornsson ES. Antibiotic susceptibility of Helicobacter pylori in Iceland. Infect Dis (Lond) 2017; 49:647-654. [PMID: 28440099 DOI: 10.1080/23744235.2017.1317359] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Increasing resistance of Helicobacter pylori (H. pylori) to antibiotics calls for constant re-evaluation of multidrug regimens that have been used to eradicate the infection. The aim of this study was to evaluate the current antibiotic susceptibility of H. pylori in an Icelandic cohort. METHODS Patients referred for gastroscopy were recruited prospectively. Those found to have a positive rapid urease test were included in the study. Susceptibility testing was conducted by the Epsilometer test (E-test) method for ampicillin, clarithromycin, levofloxacin, metronidazole and tetracycline. Results were obtained after three days of incubation in microaerophilic conditions at 37 °C, except for the metronidazole were the first 24 hours were anaerobic. RESULTS Of the 613 patients who underwent gastroscopy, 138 (23%) had a positive rapid urease test. H. pylori was successfully cultured from 105 (76%) of the urease test positive patients and the isolates were tested for antibiotic susceptibility. Five patients had prior H. pylori eradication. Antibiotic resistance for ampicillin, clarithromycin, levofloxacin, metronidazole and tetracycline was 0%, 9%, 4%, 1% and 0%, respectively. If those who had previously undergone eradication treatment were excluded, the resistance was 0%, 6%, 3%, 1% and 0%, respectively. Clarithromycin resistance was higher amongst women than men, 13% vs. 5%, however, not significantly. Clarithromycin resistance was 60% amongst those who had previously received eradication treatment compared to 6% of those who had not (p < .0001). CONCLUSIONS Clarithromycin resistance amongst the H. pylori isolates can be considered relatively low. Therefore, in the current cohort, standard triple-drug clarithromycin-containing regimen should remain the first-line treatment against H. pylori.
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Affiliation(s)
- Anna Ingibjorg Gunnarsdottir
- a Hospital Pharmacy, Landspitali-The National University Hospital of Iceland , Reykjavik , Iceland.,b Faculty of Pharmaceutical sciences , The University of Iceland , Reykjavik , Iceland
| | - Hallgrimur Gudjonsson
- c Department of Internal Medicine , Landspitali-The National University Hospital of Iceland , Reykjavik , Iceland.,d Faculty of Medicine , The University of Iceland , Reykjavik , Iceland
| | - Hjordis Hardardottir
- e Department of Clinical Microbiology , Landspitali-The National University Hospital of Iceland , Reykjavik , Iceland
| | | | - Einar Stefan Bjornsson
- c Department of Internal Medicine , Landspitali-The National University Hospital of Iceland , Reykjavik , Iceland.,d Faculty of Medicine , The University of Iceland , Reykjavik , Iceland
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Effects of Helicobacter pylori eradication on insulin resistance and metabolic parameters: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2017; 29:153-159. [PMID: 27832037 DOI: 10.1097/meg.0000000000000774] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Previous studies have shown a close relationship between Helicobacter pylori (H. pylori), insulin resistance, and altered metabolic parameters. However, the effects of H. pylori eradication on these conditions remain controversial. We carried out a systematic review and meta-analysis to evaluate the effects of H. pylori eradication on insulin resistance and metabolic parameters. METHODS We searched CENTRAL, MEDLINE, and EMBASE databases from their inception to July 2016. Insulin resistance (HOMA-IR), body weight (BW), BMI, waist circumference, triglycerides (TG), high-density and low-density lipoprotein-cholesterol (HDL-C and LDL-C), and fasting blood glucose (FBG) were compared between patients with and without H. pylori eradication using a random-effects model. We reported pooled mean differences (MD) and 95% confidence intervals (CI) for the change in outcomes. RESULTS Data from five studies showed no difference in HOMA-IR after H. pylori eradication (pooled MD=-0.52, 95% CI: -1.47 to 0.42). Eradication significantly increased BMI (MD=0.36, 95% CI: 0.11-0.60) and BW (MD=1.1, 95% CI: 0.8-1.5), but had no significant effects on TG, LDL-C, HDL-C, or FBG. CONCLUSION H. pylori eradication does not improve insulin resistance, TG, HDL-C, LDL-C, or FBG, but may increase BW and BMI. Further studies are needed to clarify the effect of H. pylori eradication on metabolism.
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Jung YD, Kim YJ, Chung WC. A Pilot Study of Helicobacter pylori Eradication Using a Polymerase Chain Reaction-based Test for Clarithromycin Resistance. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2017. [DOI: 10.7704/kjhugr.2017.17.4.200] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Yun Duk Jung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yeon-Ji Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Woo Chul Chung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Giorgio F, Ierardi E, Sorrentino C, Principi M, Barone M, Losurdo G, Iannone A, Giangaspero A, Monno R, Di Leo A. Helicobacter pylori DNA isolation in the stool: an essential pre-requisite for bacterial noninvasive molecular analysis. Scand J Gastroenterol 2016; 51:1429-1432. [PMID: 27687850 DOI: 10.1080/00365521.2016.1216592] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE Real-time polymerase chain reaction (RT-PCR) is a widely used technique for bacterial and viral infection diagnosis. Herein, we report our preliminary experience in retrieving H. pylori genetic sequences in stools and analyzing genotypic clarithromycin resistance by RT-PCR (noninvasive), with the aim of comparing this procedure with that performed on biopsy samples (invasive). MATERIALS AND METHODS After 'in vitro' demonstration of H. pylori DNA detection from pure and stool-mixed bacteria, 52 consecutive patients at the first diagnosis of infection were investigated. DNA was extracted from biopsy tissue and stool samples (THD® Fecal Test, Italy). RT-PCR was performed to detect 23S rRNA encoding bacterial subunit gene and search A2143G, A2142C, A2142G point mutations for clarithromycin resistance assessment. RESULTS RT-PCR showed H. pylori positive DNA in all infected patients with full concordance between tissue and stool detection (100%). We found A2143G mutation in 10 (19.2%), A2142G in 4 (7.7%) and A2142C in 5 (9.6%) patients; there was a full agreement between biopsy and fecal samples. A2143G was found in all the four A2142G positive cases and in three out of the five A2142C positive strains. Overall clarithromycin resistance rate in our series was 23%. CONCLUSIONS Despite the need of confirmation on large sample, stool RT-PCR analysis could represent a feasible tool to detect H. pylori DNA sequences and antibiotic resistance point mutations. As compared to tissue molecular analysis, this technique is noninvasive, with potential advantages such as improvement of patient compliance, reduction of diagnostic procedure time/cost and improvement of therapeutic outcome.
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Affiliation(s)
- Floriana Giorgio
- a Section of Gastroenterology, Department of Emergency and Organ Transplantation , University of Bari , Bari , Italy
| | - Enzo Ierardi
- a Section of Gastroenterology, Department of Emergency and Organ Transplantation , University of Bari , Bari , Italy
| | - Claudia Sorrentino
- a Section of Gastroenterology, Department of Emergency and Organ Transplantation , University of Bari , Bari , Italy
| | - Mariabeatrice Principi
- a Section of Gastroenterology, Department of Emergency and Organ Transplantation , University of Bari , Bari , Italy
| | - Michele Barone
- a Section of Gastroenterology, Department of Emergency and Organ Transplantation , University of Bari , Bari , Italy
| | - Giuseppe Losurdo
- a Section of Gastroenterology, Department of Emergency and Organ Transplantation , University of Bari , Bari , Italy
| | - Andrea Iannone
- a Section of Gastroenterology, Department of Emergency and Organ Transplantation , University of Bari , Bari , Italy
| | - Antonio Giangaspero
- a Section of Gastroenterology, Department of Emergency and Organ Transplantation , University of Bari , Bari , Italy
| | - Rosa Monno
- b Section of Microbiology, Department of Basic Medical Science, Neuroscience and Sense Organs , University of Bari , Bari , Italy
| | - Alfredo Di Leo
- a Section of Gastroenterology, Department of Emergency and Organ Transplantation , University of Bari , Bari , Italy
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Sanches BS, Martins GM, Lima K, Cota B, Moretzsohn LD, Ribeiro LT, Breyer HP, Maguilnik I, Maia AB, Rezende-Filho J, Meira AC, Pinto H, Alves E, Mascarenhas R, Passos R, de Souza JD, Trindade OR, Coelho LG. Detection of Helicobacter pylori resistance to clarithromycin and fluoroquinolones in Brazil: A national survey. World J Gastroenterol 2016; 22:7587-7594. [PMID: 27672279 PMCID: PMC5011672 DOI: 10.3748/wjg.v22.i33.7587] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2016] [Revised: 06/28/2016] [Accepted: 07/06/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate bacterial resistance to clarithromycin and fluoroquinolones in Brazil using molecular methods.
METHODS The primary antibiotic resistance rates of Helicobacter pylori (H. pylori) were determined from November 2012 to March 2015 in the Southern, South-Eastern, Northern, North-Eastern, and Central-Western regions of Brazil. Four hundred ninety H. pylori patients [66% female, mean age 43 years (range: 18-79)] who had never been previously treated for this infection were enrolled. All patients underwent gastroscopy with antrum and corpus biopsies and molecular testing using GenoType HelicoDR (Hain Life Science, Germany). This test was performed to detect the presence of H. pylori and to identify point mutations in the genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from the biopsies, multiplex amplification, and reverse hybridization.
RESULTS Clarithromycin resistance was found in 83 (16.9%) patients, and fluoroquinolone resistance was found in 66 (13.5%) patients. There was no statistical difference in resistance to either clarithromycin or fluoroquinolones (P = 0.55 and P = 0.06, respectively) among the different regions of Brazil. Dual resistance to clarithromycin and fluoroquinolones was found in 4.3% (21/490) of patients. The A2147G mutation was present in 90.4% (75/83), A2146G in 16.9% (14/83) and A2146C in 3.6% (3/83) of clarithromycin-resistant patients. In 10.8% (9/83) of clarithromycin-resistant samples, more than 01 mutation in the 23S rRNA gene was noticed. In fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. D91N mutation was observed in 34.8% (23/66), D91G in 18.1% (12/66), N87K in 16.6% (11/66) and D91Y in 13.6% (9/66) of cases. Among fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test.
CONCLUSION The H. pylori clarithromycin resistance rate in Brazil is at the borderline (15%-20%) for applying the standard triple therapy. The fluoroquinolone resistance rate (13.5%) is equally concerning.
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Xuan SH, Wu LP, Zhou YG, Xiao MB. Detection of clarithromycin-resistant Helicobacter pylori in clinical specimens by molecular methods: A review. J Glob Antimicrob Resist 2016; 4:35-41. [PMID: 27436390 DOI: 10.1016/j.jgar.2016.01.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2015] [Revised: 01/06/2016] [Accepted: 01/08/2016] [Indexed: 12/17/2022] Open
Abstract
Various molecular methods have been developed to rapidly detect clarithromycin (CLR) resistance in Helicobacter pylori isolates in clinical specimens. All of these assays for detecting CLR resistance in H. pylori are based on detection of mutations in the 23S rRNA gene. In this article, we summarise current knowledge regarding the detection of H. pylori CLR resistance in clinical specimens by molecular tests. The available data showed that restriction fragment length polymorphism (RFLP), 3'-mismatch PCR, DNA sequencing, the PCR line probe assay (PCR-LiPA) and fluorescence in situ hybridisation assay (FISH) are able to detect CLR-resistant H. pylori in clinical specimens with excellent specificity and sensitivity. However, several factors limit their clinical application, including fastidious, time-consuming preparation and low-throughput as well as carrying a risk of contamination. Furthermore, as an invasive method, FISH is not suitable for children or the elderly. Among the molecular methods, one that is most promising for the future is real-time PCR probe hybridisation technology using fluorescence resonance energy transfer (FRET) probes, which can rapidly detect CLR resistance with high sensitivity and specificity in biopsies and stool specimens, even though mixed infections are present in clinical specimens. Moreover, due to the advantages that this method is simple, rapid and economical, real-time PCR is technically feasible for clinical application in small- and medium-sized hospitals in developing countries. Second, with high sensitivity, specificity and throughput, DNA chips will also be a valuable tool for detecting resistant H. pylori isolates from cultures and clinical specimens.
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Affiliation(s)
- Shi-Hai Xuan
- Department of Clinical Laboratory, The Affiliated Dongtai Hospital of Nantong University, Dongtai 224200, China
| | - Li-Pei Wu
- Department of Clinical Laboratory, The Affiliated Dongtai Hospital of Nantong University, Dongtai 224200, China
| | - Yu-Gui Zhou
- Department of Clinical Laboratory, The Affiliated Dongtai Hospital of Nantong University, Dongtai 224200, China
| | - Ming-Bing Xiao
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, China.
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Hsu PI, Kao SS, Wu DC, Chen WC, Peng NJ, Yu HC, Wang HM, Lai KH, Cheng JS, Chen A, Chuah SK, Tsay FW. A Randomized Controlled Study Comparing Reverse Hybrid Therapy and Standard Triple Therapy for Helicobacter pylori Infection. Medicine (Baltimore) 2015; 94:e2104. [PMID: 26632893 PMCID: PMC4674196 DOI: 10.1097/md.0000000000002104] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Reverse hybrid therapy is an 1-step 2-phase treatment for Helicobacter pylori (H. pylori) infection with less cost than standard triple therapy. We conducted a randomized, controlled study to compare the efficacies of standard triple therapy and reverse hybrid therapy in the treatment of H. pylori infection. From October 2012 to March 2015, consecutive H. pylori-infected subjects were randomly allocated to receive either a reverse hybrid therapy (pantoprazole plus amoxicillin for 12 days and clarithromycin plus metronidazole for the initial 7 days) or a standard triple therapy (pantoprazole plus amoxicillin and clarithromycin for 12 days). H. pylori status was assessed 6 weeks after treatment. Additionally, antibiotic resistances and host CYP2C19 genotypes were examined and analyzed. A total of 440 H. pylori-infected patients were randomly assigned to receive either a reverse hybrid (n = 220) or a standard triple therapy (n = 220). The reverse hybrid group had a higher eradication rate than standard triple group either by intention-to-treat (93.6% vs. 86.8%; P = 0.016) or per-protocol analysis (95.7% vs. 88.3%; P = 0.005). The 2 patient groups exhibited similar frequencies of overall adverse events (14.1% vs. 9.5%) and drug compliance (96.8% vs. 98.6%). Clarithromycin resistance was an independent risk factor predicting eradication failure in standard triple group (P < 0.001), but not in reverse hybrid group. CYP2C19 genotypes did not affect the eradication rates in both groups. Reverse hybrid therapy can be considered for first-line treatment of H. pylori infection since the new therapy achieves a higher eradication rate than standard triple therapy with similar tolerability and less pharmaceutical cost.
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Affiliation(s)
- Ping-I Hsu
- From the Division of Gastroenterology, Kaohsiung, Taiwan (P-IH, S-SK, W-CC, H-CY, H-MW, K-HL, J-S C, F-WT); Department of Internal Medicine, Kaohsiung, Taiwan; Department of Nuclear Medicine, Kaohsiung, Taiwan (N-JP); Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan; Division of Gastroenterology, Kaohsiung, Taiwan (D-CW); Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Medicine, Kaohsiung, Taiwan (D-CW); Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Biomedical Sciences, Kaohsiung, Taiwan (AC), National Sun Yat-Sen University, Kaohsiung, Taiwan; Division of Hepato-Gastroenterology, Kaohsiung, Taiwan (S-KC); and Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Kim SY, Choi DJ, Chung JW. Antibiotic treatment for Helicobacter pylori: Is the end coming? World J Gastrointest Pharmacol Ther 2015; 6:183-198. [PMID: 26558152 PMCID: PMC4635158 DOI: 10.4292/wjgpt.v6.i4.183] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 08/01/2015] [Accepted: 09/28/2015] [Indexed: 02/06/2023] Open
Abstract
Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori) has been associated with gastro-duodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacillus. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication.
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Losurdo G, Leandro G, Principi M, Giorgio F, Montenegro L, Sorrentino C, Ierardi E, Di Leo A. Sequential vs. prolonged 14-day triple therapy for Helicobacter pylori eradication: the meta-analysis may be influenced by 'geographical weighting'. Int J Clin Pract 2015; 69:1112-20. [PMID: 26138290 DOI: 10.1111/ijcp.12687] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Sequential therapy is a first-line regimen obtaining satisfactory Helicobacter pylori eradication. Triple therapy prolongation improves the success rate even if a recent meta-analysis showed satisfying results only for the 14-day regimen. Studies from Africa and North America were unavailable in previous meta-analyses. AIM To perform a meta-analysis comparing sequential vs. prolonged 14-day triple therapy with regard to 'geographic weighting' by considering subgroups analysis according to metronidazole/clarithromycin low and high resistance areas. METHODS Based on PRISMA recommendations, we considered all first-line clinical studies from 2003 to November 2014. Randomised clinical trials (RCTs) were included by a search on PubMed, MEDLINE, Science Direct, EMBASE. Data on eradication rates were expressed as ITT. Risk ratio (RR), pooled RR and 95% confidence intervals were calculated by the Mantel-Haenszel method. Data were entered into RevMan 5.2 software (Nordic Cochrane Centre) using a random-effects model. RESULTS Databases identified 194 studies; seven met the inclusion criteria. Overall results showed a similar effectiveness of the two regimens considered (RR = 0.99; 95% CI = 0.94-1.05; p = 0.75). In areas with high resistance to clarithromycin, sequential was superior to 14-day triple therapy (RR = 0.95; 95% CI = 0.90-1.00; p = 0.03). In areas with high metronidazole resistance, sequential and 14-day triple therapy were equivalent (RR = 0.99; 95% CI = 0.91-1.08; p = 0.82). CONCLUSIONS 'Geographic weighting' could be the main factor affecting the lack of differences between sequential and 14-day triple therapy outcomes.
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Affiliation(s)
- G Losurdo
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - G Leandro
- Gastroenterological Department, IRCCS "De Bellis" Hospital, Castellana Grotte, Italy
| | - M Principi
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - F Giorgio
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - L Montenegro
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - C Sorrentino
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - E Ierardi
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - A Di Leo
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
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Kishikawa H, Kimura K, Takarabe S, Kaida S, Nishida J. Helicobacter pylori Antibody Titer and Gastric Cancer Screening. DISEASE MARKERS 2015; 2015:156719. [PMID: 26494936 PMCID: PMC4606161 DOI: 10.1155/2015/156719] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2015] [Accepted: 09/06/2015] [Indexed: 02/07/2023]
Abstract
The "ABC method" is a serum gastric cancer screening method, and the subjects were divided based on H. pylori serology and atrophic gastritis as detected by serum pepsinogen (PG): Group A [H. pylori (-) PG (-)], Group B [H. pylori (+) PG (-)], Group C [H. pylori (+) PG (+)], and Group D [H. pylori (-) PG (+)]. The risk of gastric cancer is highest in Group D, followed by Groups C, B, and A. Groups B, C, and D are advised to undergo endoscopy, and the recommended surveillance is every three years, every two years, and annually, respectively. In this report, the reported results with respect to further risk stratification by anti-H. pylori antibody titer in each subgroup are reviewed: (1) high-negative antibody titer subjects in Group A, representing posteradicated individuals with high risk for intestinal-type cancer; (2) high-positive antibody titer subjects in Group B, representing active inflammation with high risk for diffuse-type cancer; and (3) low-positive antibody titer subjects in Group C, representing advanced atrophy with increased risk for intestinal-type cancer. In these subjects, careful follow-up with intervals of surveillance of every three years in (1), every two years in (2), and annually in (3) should be considered.
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Affiliation(s)
- Hiroshi Kishikawa
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba 272-8513, Japan
| | - Kayoko Kimura
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba 272-8513, Japan
| | - Sakiko Takarabe
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba 272-8513, Japan
| | - Shogo Kaida
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba 272-8513, Japan
| | - Jiro Nishida
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba 272-8513, Japan
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Tongtawee T, Dechsukhum C, Leeanansaksiri W, Kaewpitoon S, Kaewpitoon N, Loyd RA, Matrakool L, Panpimanmas S. Effect of Pretreatment with Lactobacillus delbrueckii and Streptococcus thermophillus on Tailored Triple Therapy for Helicobacter pylori Eradication: A Prospective Randomized Controlled Clinical Trial. Asian Pac J Cancer Prev 2015; 16:4885-90. [DOI: 10.7314/apjcp.2015.16.12.4885] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Tsay FW, Wu DC, Kao SS, Tsai TJ, Lai KH, Cheng JS, Chan HH, Wang HM, Tsai WL, Tseng HH, Peng NJ, Hsu PI. Reverse sequential therapy achieves a similar eradication rate as standard sequential therapy for Helicobacter pylori eradication: a randomized controlled trial. Helicobacter 2015; 20:71-7. [PMID: 25495272 DOI: 10.1111/hel.12176] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS Sequential therapy is a two-step therapy achieving a promising eradication rate for Helicobacter pylori infection. The rationale of sequential method has been proposed that amoxicillin weakens bacterial cell walls in the initial phase of treatment, preventing the development of drug efflux channels for clarithromycin and metronidazole used in the second phase. The aim of this prospective, randomized, controlled study was to investigate whether the efficacy of reverse sequential therapy was noninferior to sequential therapy in the treatment of H. pylori infection. METHODS From January 2009 to December 2010, consecutive H. pylori-infected patients were randomly assigned to receive either sequential therapy (a 5-day dual therapy with pantoprazole plus amoxicillin, followed by a 5-day triple therapy with pantoprazole plus clarithromycin and metronidazole) or reverse sequential therapy (a 5-day triple therapy with pantoprazole plus clarithromycin and metronidazole, followed by a 5-day dual therapy with pantoprazole plus amoxicillin). H. pylori status was examined 6 weeks after the end of treatment by rapid urease and histology or urea breath test. RESULTS One hundred and twenty-two H. pylori-infected participants were randomized to receive sequential (n = 60) or reverse sequential therapy (n = 62). The eradication rates, by intention-to-treat analysis, were similar: 91.9% (95% confidence interval (CI): 85.1-98.7%) for sequential therapy and 96.7% (95% CI: 92.2-101.2%) for reverse sequential therapy (p = .44). Per-protocol analysis also showed similar results: 91.8% (95% CI: 84.9-98.7%) for sequential group and 96.7% (95% CI: 92.2-101.2%) for reverse sequential therapy (p = .43). The two treatments exhibited comparable frequencies of adverse events (11.3% vs 6.7%, respectively) and drug compliance (98.4% vs 100%, respectively). The overall resistance rates of antibiotics were clarithromycin 10.5%, amoxicillin 0%, and metronidazole 44.2% of patients, respectively. The dual resistance rate of clarithromycin and metronidazole was 4.2%. Both therapies achieved a high eradication rate for clarithromycin-resistant strains (100% vs 100%, respectively) and metronidazole-resistant strains (81.8% vs 95%, respectively) by intention-to-treat analysis. CONCLUSIONS Ten-day reverse sequential therapy and standard sequential therapy are equally effective for H. Pylori eradication. The finding indicates that the sequence of antibiotics administered in sequential therapy does not influence the efficacy of the treatment.
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Affiliation(s)
- Feng-Woei Tsay
- Division of Gastroenterology, Department of internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan; Cheng Shiu University, Kaohsiung, Taiwan
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Randomized controlled trial comparing 7-day triple, 10-day sequential, and 7-day concomitant therapies for Helicobacter pylori infection. Antimicrob Agents Chemother 2014; 58:5936-42. [PMID: 25070099 DOI: 10.1128/aac.02922-14] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
With the rising prevalence of antimicrobial resistance, the failure rate of the standard triple therapy for Helicobacter pylori infection is increasing. Sequential therapy and concomitant therapy have been recommended to replace standard triple therapy for H. pylori eradication in regions with high clarithromycin resistance. The aim of this prospective, randomized, and controlled study was to simultaneously assess the efficacies of 10-day sequential and 7-day concomitant therapies versus a 7-day standard triple therapy for treating H. pylori infection. Consecutive H. pylori-infected subjects were randomly assigned to a 7-day standard triple therapy (pantoprazole, clarithromycin, and amoxicillin for 7 days), a 10-day sequential therapy (pantoprazole and amoxicillin for 5 days, followed by pantoprazole, clarithromycin, and metronidazole for a further 5 days), or a 7-day quadruple therapy (pantoprazole, clarithromycin, amoxicillin, and metronidazole for 7 days). H. pylori status was confirmed 6 weeks after therapy. Three hundred seven H. pylori-infected participants were randomized to receive triple (n = 103), sequential (n = 102), or concomitant (n = 102) therapies. The eradication rates by an intention-to-treat analysis in the three treatment groups were 81.6% (95% confidence interval [CI], 74.1% to 89.0%), 89.2% (95% CI, 83.2% to 95.2%), and 94.1% (95% CI, 89.5% to 98.7%). The seven-day concomitant therapy had a higher eradication rate than did the 7-day triple therapy (difference, 12.5%; 95% CI, 3.7% to 21.3%). There were no significant differences in the eradication rates between the sequential and standard triple therapies. All three treatments exhibited similar frequencies of adverse events (8.7%, 8.8%, and 13.7%, respectively) and drug compliance (99.0%, 98.0%, and 100.0%, respectively). In conclusion, the seven-day concomitant therapy is superior to the 7-day standard triple therapy for H. pylori eradication. Additionally, it is less complex than the 10-day sequential therapy because the drugs are not changed halfway through the treatment course. (This study has been registered at ClinicalTrials.gov under registration no. NCT1769365.).
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Alfizah H, Norazah A, Hamizah R, Ramelah M. Resistotype of Helicobacter pylori isolates: the impact on eradication outcome. J Med Microbiol 2014; 63:703-709. [PMID: 24757218 DOI: 10.1099/jmm.0.069781-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Antibiotic resistance is increasing worldwide, and it has been regarded as the main factor reducing the efficacy of Helicobacter pylori therapy. The aim of this study was to determine the phenotype and genotype of antibiotic-resistant strains of H. pylori in the Malaysian population and to evaluate the impact of antibiotic resistance to eradication outcome. One hundred and sixty-one H. pylori isolates were analysed in this study. Metronidazole, clarithromycin, fluoroquinolone, amoxicillin and tetracycline susceptibilities were determined by Etest. PCR followed by DNA sequencing was carried out to determine mutations. The medical records of the patients infected with resistant strains were reviewed to determine the eradication outcome. Metronidazole resistance was encountered in 36.6 % of H. pylori isolates, whereas clarithromycin and fluoroquinolone resistance was observed in 1.2 and 1.9 % of isolates, respectively. All strains tested were susceptible to amoxicillin and tetracycline. Frameshift and nonsense mutations in rdxA and frxA genes resulting in stop codons contributed to metronidazole resistance, which leads to reduced eradication efficacy. A2142G and A2143G mutations of 23S rRNA were identified as causing failure of the eradication therapy. Mutation at either codon 87 or 91 of the gyrA gene was identified in fluoroquinolone-resistant strains. However, the effect of resistance could not be assessed. This study showed that frameshift and nonsense mutations in rdxA or frxA genes and point mutations in the 23S rRNA affected the efficacy of H. pylori eradication therapy.
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Affiliation(s)
- Hanafiah Alfizah
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Malaysia
| | - Ahmad Norazah
- Bacteriology Unit, Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Malaysia
| | - Razlan Hamizah
- Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Malaysia
| | - Mohamed Ramelah
- Centre for Innovative Collaboration, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia
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Song M, Ang TL. Second and third line treatment options for Helicobacter pylori eradication. World J Gastroenterol 2014; 20:1517-1528. [PMID: 24587627 PMCID: PMC3925860 DOI: 10.3748/wjg.v20.i6.1517] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Revised: 10/29/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori is a highly successful bacterium with a high global prevalence and the infection carries significant disease burden. It is also becoming increasingly difficult to eradicate and the main reason for this is growing primary antibiotic resistance rates in a world where antibiotics are frequently prescribed and readily available. Despite knowing much more about the bacterium since its discovery, such as its genomic makeup and pathogenesis, we have seen declining treatment success. Therefore, clinicians today must be prepared to face one, two or even multiple treatment failures, and should be equipped with sufficient knowledge to decide on the appropriate salvage therapy when this happens. This article discusses the factors contributing to treatment failure and reviews the second and third-line treatment strategies that have been investigated. Established empiric second line treatment options include both bismuth based quadruple therapy and levofloxacin based triple therapy. Antibiotic testing is recommended prior to initiating third line treatment. In the event that antibiotic susceptibility testing is unavailable, third line treatment options include rifabutin, rifaximin and sitafloxacin based therapies.
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Garza-González E, Perez-Perez GI, Maldonado-Garza HJ, Bosques-Padilla FJ. A review of Helicobacter pylori diagnosis, treatment, and methods to detect eradication. World J Gastroenterol 2014; 20:1438-1449. [PMID: 24587620 PMCID: PMC3925853 DOI: 10.3748/wjg.v20.i6.1438] [Citation(s) in RCA: 127] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Revised: 11/15/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) affects nearly half of the world’s population and, thus, is one of the most frequent and persistent bacterial infections worldwide. H. pylori is associated with peptic ulcer disease, gastric ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Various diagnostic methods exist to detect infection, and the choice of one method or another depends on several factors, such as accessibility, advantages and disadvantages of each method, cost, and the age of patients. Once H. pylori infection is diagnosed, the clinician decides whether treatment is necessity, according to the patient’s clinical condition. Typically, eradication of H. pylori is recommended for treatment and prevention of the infection. Cure rates with the standard triple therapy are acceptable, and effective quadruple therapies, sequential therapies, and concomitant therapies have been introduced as key alternatives to treat H. pylori infection. In this work, we review the main diagnostic methods used to identify H. pylori infection and to confirm eradication of infection. In addition, key factors related to treatment are reviewed.
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De Francesco V, Zullo A, Giorgio F, Saracino I, Zaccaro C, Hassan C, Ierardi E, Di Leo A, Fiorini G, Castelli V, Lo Re G, Vaira D. Change of point mutations in Helicobacter pylori rRNA associated with clarithromycin resistance in Italy. J Med Microbiol 2013; 63:453-457. [PMID: 24344205 DOI: 10.1099/jmm.0.067942-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Primary clarithromycin resistance is the main factor affecting the efficacy of Helicobacter pylori therapy. This study aimed: (i) to assess the concordance between phenotypic (culture) and genotypic (real-time PCR) tests in resistant strains; (ii) to search, in the case of disagreement between the methods, for point mutations other than those reported as the most frequent in Europe; and (iii) to compare the MICs associated with the single point mutations. In order to perform real-time PCR, we retrieved biopsies from patients in whom H. pylori infection was successful diagnosed by bacterial culture and clarithromycin resistance was assessed using the Etest. Only patients who had never been previously treated, and with H. pylori strains that were either resistant exclusively to clarithromycin or without any resistance, were included. Biopsies from 82 infected patients were analysed, including 42 strains that were clarithromycin resistant and 40 that were clarithromycin susceptible on culture. On genotypic analysis, at least one of the three most frequently reported point mutations (A2142C, A2142G and A2143G) was detected in only 23 cases (54.8%), with a concordance between the two methods of 0.67. Novel point mutations (A2115G, G2141A and A2144T) were detected in a further 14 out of 19 discordant cases, increasing the resistance detection rate of PCR to 88% (P<0.001; odds ratio 6.1, 95% confidence interval 2-18.6) and the concordance to 0.81. No significant differences in MIC values among different point mutations were observed. This study suggests that: (i) the prevalence of the usually reported point mutations may be decreasing, with a concomitant emergence of new mutations; (ii) PCR-based methods should search for at least six point mutations to achieve good accuracy in detecting clarithromycin resistance; and (iii) none of the tested point mutations is associated with significantly higher MIC values than the others.
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Affiliation(s)
| | - Angelo Zullo
- Gastroenterology and Digestive Endoscopy, 'Nuovo Regina Margherita' Hospital, Rome, Italy
| | - Floriana Giorgio
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Ilaria Saracino
- Department of Clinical Medicine, University of Bologna, Bologna, Italy
| | - Cristina Zaccaro
- Department of Clinical Medicine, University of Bologna, Bologna, Italy
| | - Cesare Hassan
- Gastroenterology and Digestive Endoscopy, 'Nuovo Regina Margherita' Hospital, Rome, Italy
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Giulia Fiorini
- Department of Clinical Medicine, University of Bologna, Bologna, Italy
| | | | - Giovanna Lo Re
- Department of Clinical Medicine, University of Bologna, Bologna, Italy
| | - Dino Vaira
- Department of Clinical Medicine, University of Bologna, Bologna, Italy
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Huang J, Zhou L, Geng L, Yang M, Xu XW, Ding ZL, Mao M, Wang ZL, Li ZL, Li DY, Gong ST. Randomised controlled trial: sequential vs. standard triple therapy for Helicobacter pylori infection in Chinese children-a multicentre, open-labelled study. Aliment Pharmacol Ther 2013; 38:1230-5. [PMID: 24117692 DOI: 10.1111/apt.12516] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2013] [Revised: 05/01/2013] [Accepted: 09/12/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Studies have showed that 10-day sequential treatment regimen achieved higher Helicobacter pylori eradication rate than standard triple therapies. AIM To compare a 10-day sequential therapy and standard triple therapy in Chinese children with H. pylori infection. METHODS A prospective, multicentre, open-label, randomised controlled trial was conducted in four tertiary medical centres in China. Children with H. pylori gastritis were randomly assigned to a 10-day sequential therapy consisting of omeprazole and amoxicillin for 5 days followed by omeprazole, clarithromycin and metronidazole for the remaining 5 days, or 7-day or 10-day standard triple therapy comprising of omeprazole, amoxicillin and clarithromycin. H. pylori eradication was assessed by H. pylori stool antigen test. RESULTS A total of 360 patients were included. The eradication rate achieved with the 10-day sequential therapy was significantly higher than either the 7-day or 10-day standard triple treatment, either by the intention-to-treat analysis (81.4% vs. 61.9% or 67.7%, P < 0.05) or per-protocol analysis (89.7% vs. 70.8% or 77.8%, P < 0.05). CONCLUSIONS The 10-day sequential regimen was significantly more effective than standard 7-day or 10-day triple regimens in eradicating H. pylori infection in Chinese children.
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Affiliation(s)
- J Huang
- Guangzhou Women and Children's Medical Center of Guangzhou Medical College, Guangzhou, China
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Giorgio F, Principi M, De Francesco V, Zullo A, Losurdo G, Di Leo A, Ierardi E. Primary clarithromycin resistance to Helicobacter pylori: Is this the main reason for triple therapy failure? World J Gastrointest Pathophysiol 2013; 4:43-46. [PMID: 23946886 PMCID: PMC3740258 DOI: 10.4291/wjgp.v4.i3.43] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2013] [Revised: 06/20/2013] [Accepted: 07/05/2013] [Indexed: 02/06/2023] Open
Abstract
Conventional triple therapies for Helicobacter pylori (H. pylori) eradication have recently shown a disappointing reduction in effectiveness in many countries. The main reason for failure was found to be bacterial resistance to one of the most commonly used antibiotics, clarithromycin. An additional problem for conventional triple therapy is the high rate of resistance to metronidazole found in Europe, America and Asia. In Italy, in the last 15 years a 2-fold increase in resistance has occurred. A recent study of the whole of Italy included about 20 patients from each region at the first endoscopic diagnosis of H. pylori infection. The most surprising result was the patchy distribution of resistance, which was almost absent in two regions (one northern and one southern), although the highest prevalence was found in some regions of the South. In the paediatric population we found a 25% prevalence of resistance in a sample of H. pylori positive children observed between 2002 and 2007, mirroring data obtained in southern European countries. Clarithromycin resistance assessment is currently based on phenotypic detection performed after culture the agar dilution method or E-test, and genotypic methods based on polymerase chain reaction (PCR). In a recent comparative study we found a 71.2% agreement between the two methods. Culture-free techniques are highly accurate in finding even minimal traces of genotypically resistant strains. Moreover, PCR-based tools are accurate in detecting a heteroresistant status, defined as the co-existence of some strains that are susceptible and some resistant to the same antibiotic in an individual patient. Three point mutations, namely A2143G, A2142G and A2142C, are responsible for 90% of cases of primary clarithromycin resistance in H. pylori strains isolated in Western countries, although we previously demonstrated that the presence of the A2143G mutation, but not A2142G or A2142C, significantly lowered the H. pylori eradication rate. Treatment failure has considerable cost/benefit implications because of “waste” of National Health System and patient resources, in terms of drugs, further diagnostic tests and medical examination expenses. Therefore, in future it would be very useful to be able to test for clarithromycin resistance before starting conventional triple therapy. Hopefully, fast, effective non-invasive tests may soon be devised to determine this condition.
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Lee JW, Kim N, Kim JM, Nam RH, Chang H, Kim JY, Shin CM, Park YS, Lee DH, Jung HC. Prevalence of primary and secondary antimicrobial resistance of Helicobacter pylori in Korea from 2003 through 2012. Helicobacter 2013; 18:206-14. [PMID: 23241101 DOI: 10.1111/hel.12031] [Citation(s) in RCA: 168] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Antimicrobial resistance of Helicobacter pylori (H. pylori) affects the efficacy of eradication therapy. The aim of this study was to estimate the prevalence of primary and secondary resistance of H. pylori isolates to antibiotics and to characterize the risk factors associated with antimicrobial resistance in Korea. MATERIALS AND METHODS This study was performed during the period of 2003-2012. Primary resistance was evaluated from 347 patients without any history of eradication, and secondary resistance was evaluated in 86 patients from whom H. pylori was cultured after failure of eradication. Minimal inhibitory concentration test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, levofloxacin, and moxifloxacin using agar dilution method. Primary and secondary resistance rates of H. pylori to 7 antibiotics were evaluated and risk factors for the antibiotic resistance were analyzed. RESULTS Increase in the primary resistance rate was found in amoxicillin (6.3-14.9%, p = .051), clarithromycin (17.2-23.7%, p = .323), and both of levofloxacin and moxifloxacin (4.7-28.1%, p = .002) during the study period. Secondary resistance rate significantly increased in metronidazole, levofloxacin, and moxifloxacin. Increase of resistance occurred after initial failure of eradication therapy in case of clarithromycin (p < .001), azithromycin (p < .001), levofloxacin (p = .011), and moxifloxacin (p = .020). Multivariable analyses showed that clarithromycin, azithromycin, levofloxacin, and moxifloxacin resistance was associated with previous eradication treatment history. CONCLUSIONS The increased primary and secondary antibiotic resistance of H. pylori in Korea is ongoing, and it will become a significant limitation for effective eradication of H. pylori in the future.
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Affiliation(s)
- Jung Won Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
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Validation of a fluorescence in situ hybridization method using peptide nucleic acid probes for detection of Helicobacter pylori clarithromycin resistance in gastric biopsy specimens. J Clin Microbiol 2013; 51:1887-93. [PMID: 23596234 DOI: 10.1128/jcm.00302-13] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Here, we evaluated a previously established peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) method as a new diagnostic test for Helicobacter pylori clarithromycin resistance detection in paraffin-embedded gastric biopsy specimens. Both a retrospective study and a prospective cohort study were conducted to evaluate the specificity and sensitivity of a PNA-FISH method to determine H. pylori clarithromycin resistance. In the retrospective study (n = 30 patients), full agreement between PNA-FISH and PCR-sequencing was observed. Compared to the reference method (culture followed by Etest), the specificity and sensitivity of PNA-FISH were 90.9% (95% confidence interval [CI], 57.1% to 99.5%) and 84.2% (95% CI, 59.5% to 95.8%), respectively. In the prospective cohort (n = 93 patients), 21 cases were positive by culture. For the patients harboring clarithromycin-resistant H. pylori, the method showed sensitivity of 80.0% (95% CI, 29.9% to 98.9%) and specificity of 93.8% (95% CI, 67.7% to 99.7%). These values likely represent underestimations, as some of the discrepant results corresponded to patients infected by more than one strain. PNA-FISH appears to be a simple, quick, and accurate method for detecting H. pylori clarithromycin resistance in paraffin-embedded biopsy specimens. It is also the only one of the methods assessed here that allows direct and specific visualization of this microorganism within the biopsy specimens, a characteristic that allowed the observation that cells of different H. pylori strains can subsist in very close proximity in the stomach.
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Abdollahi H, Savari M, Zahedi MJ, Moghadam SD, Hayatbakhsh Abasi M. Detection of A2142C, A2142G, and A2143G Mutations in 23s rRNA Gene Conferring Resistance to Clarithromycin among Helicobacter pylori Isolates in Kerman, Iran. IRANIAN JOURNAL OF MEDICAL SCIENCES 2013; 2:430-5. [PMID: 23359224 DOI: 10.1002/dta.162] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND Clarithromycin resistance in Helicbacter pylori has been found to be associated with point mutations in 23s rRNA gene leads to reduced affinity of the antibiotic to its ribosomal target or changing the site of methylation. The aim of this study was to determine the most important point mutations in 23s rRNA gene in H. pylori that are closely related to clarithromycin resistance among such isolates. METHODS Sixty three H. pylori isolates, obtained from gastric biopsy speciemens in Kerman, Iran, were used to evaluate their susceptibility to clarithromycin by disk diffusion test, and to detect the most common point mutations in 23s rRNA gene associated with clarithromycin resistance by Polymerase chain reaction-amplification and restriction fragment length polymorphism (PCR-RFLP) and 3'-mismatch PCR. RESULTS 31.7% of the H. pylori isolates were resistant to clarithromycin, and each of the resistant isolate had at least one of the most common point mutations in 23s rRNA gene associated with calrithromycin resistance. CONCLUSION According to our results three common point mutation in 23s rRNA gene in H. pylori are closely related to clarithromycin resistance. There was an absolute relation between 23s rRNA gene point mutations and clarithromycin resistance in this study. Helicbacter pylori resistance to clarithromycin can cause failure in the eradications of the bacteria. The resistance of the bacteria is expanding in most parts of the world including Iran.
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Affiliation(s)
- Hamid Abdollahi
- Department of Medical Microbiology, Virology & Immunology, Kerman University of Medical Sciences, Kerman, Iran
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Kupcinskas L, Rasmussen L, Jonaitis L, Kiudelis G, Jørgensen M, Urbonaviciene N, Tamosiunas V, Kupcinskas J, Miciuleviciene J, Kadusevicius E, Berg D, Andersen LP. Evolution ofHelicobacter pylorisusceptibility to antibiotics during a 10-year period in Lithuania. APMIS 2012; 121:431-6. [DOI: 10.1111/apm.12012] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2012] [Accepted: 09/20/2012] [Indexed: 12/15/2022]
Affiliation(s)
- Limas Kupcinskas
- Institute for Digestive Research; Lithuanian University of Health Sciences; Kaunas; Lithuania
| | - Lone Rasmussen
- Department of Clinical Microbiology 9301; Copenhagen University Hospital; Rigshospitalet; Copenhagen; Denmark
| | - Laimas Jonaitis
- Institute for Digestive Research; Lithuanian University of Health Sciences; Kaunas; Lithuania
| | - Gediminas Kiudelis
- Institute for Digestive Research; Lithuanian University of Health Sciences; Kaunas; Lithuania
| | - Marianne Jørgensen
- Department of Clinical Microbiology 9301; Copenhagen University Hospital; Rigshospitalet; Copenhagen; Denmark
| | - Neringa Urbonaviciene
- Institute for Digestive Research; Lithuanian University of Health Sciences; Kaunas; Lithuania
| | - Vytas Tamosiunas
- Department of Biology; Faculty of Natural Sciences; Vilnius Pedagogical University; Vilnius; Lithuania
| | - Juozas Kupcinskas
- Institute for Digestive Research; Lithuanian University of Health Sciences; Kaunas; Lithuania
| | - Jolanta Miciuleviciene
- Institute for Digestive Research; Lithuanian University of Health Sciences; Kaunas; Lithuania
| | - Edmundas Kadusevicius
- Department of Basic and Clinical Pharmacology; Lithuanian University of Health Sciences; Kaunas; Lithuania
| | - Douglas Berg
- Department of Molecular Microbiology; Washington University Medical School; St. Louis; MO; USA
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Talebi Bezmin Abadi A, Ghasemzadeh A, Taghvaei T, Mobarez AM. Primary resistance of Helicobacter pylori to levofloxacin and moxifloxacine in Iran. Intern Emerg Med 2012; 7:447-52. [PMID: 21437583 DOI: 10.1007/s11739-011-0563-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2011] [Accepted: 03/10/2011] [Indexed: 01/01/2023]
Abstract
The increase in the prevalence of antibiotic resistance in Helicobacter pylori had a drastic effect on successful treatment. Up-to-date information on H. pylori antibiotic therapy in Iran is still limited. In this study, we aim to determine the prevalence of antibiotic resistance among the H. pylori strains. Furthermore, the possibility of using fluoroquinolones for antibiotic treatment was investigated. Antral biopsy specimens obtained from dyspeptic patients were investigated for H. pylori. Bacterial culture and susceptibility tests were done based on standard methods. H. pylori ATCC 43504 was used as a quality control. In the current study, 30 H. pylori strains were selected randomly and retested to confirm our susceptibility tests. Of 170 patients, 150 were identified as positive for H. pylori (88.2%). In this study, 150 single colonies of H. pylori strains [81 women (54%), 69 men (46%); mean age 38.6; aged 21-70 years] were collected. Primary resistance of H. pylori isolates were clarithromycin (34%), metronidazole (78.6%), tetracycline (9.3%), amoxicillin (10%), levofloxacin (5.3%) and moxifloxacine (4.6%). In conclusion, our results show that we are confronting a new generation of resistant strains of H. pylori in Iran. This alarming finding indicates an urgent need for introduction of new effective antibiotics in our country. Since the majority of clinicians prefer to continue with the ineffective antibiotics as therapeutic regimens, they must also be prepared to deal with treatment failures.
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Affiliation(s)
- Amin Talebi Bezmin Abadi
- Department of Bacteriology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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Helicobacter pylori Eradication Therapies in the Era of Increasing Antibiotic Resistance: A Paradigm Shift to Improved Efficacy. Gastroenterol Res Pract 2012; 2012:757926. [PMID: 22778723 PMCID: PMC3388348 DOI: 10.1155/2012/757926] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2012] [Accepted: 05/08/2012] [Indexed: 12/13/2022] Open
Abstract
With the rising prevalence of antimicrobial resistance, the eradication rates of Helicobacter pylori (H. pylori) with standard treatments are decreasing to unacceptable levels (i.e., ≤80%) in most countries. After these disappointing results, several authorities have proposed that infection with H. pylori should be approached and treated as any other bacterial infectious disease. This implicates that clinicians should prescribe empirical treatments yielding a per protocol eradication of at least 90%. In recent years several treatments producing ≥90% cure rates have been proposed including sequential therapy, concomitant quadruple therapy, hybrid (dual-concomitant) therapy, and bismuth-containing quadruple therapy. These treatments are likely to represent the recommended first-line treatments in the near future. In the present paper, we are considering a series of critical issues regarding currently available means and approaches for the management of H. pylori infection. Clinical needs and realistic endpoints are taken into account. Furthermore, emerging strategies for the eradication of H. pylori and the existing evidence of their clinical validation and widespread applicability are discussed.
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Helicobacter pylori Eradication Therapies in the Era of Increasing Antibiotic Resistance: A Paradigm Shift to Improved Efficacy. Gastroenterol Res Pract 2012. [PMID: 22778723 DOI: 10.1155/2012/757926.epub2012jun19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
With the rising prevalence of antimicrobial resistance, the eradication rates of Helicobacter pylori (H. pylori) with standard treatments are decreasing to unacceptable levels (i.e., ≤80%) in most countries. After these disappointing results, several authorities have proposed that infection with H. pylori should be approached and treated as any other bacterial infectious disease. This implicates that clinicians should prescribe empirical treatments yielding a per protocol eradication of at least 90%. In recent years several treatments producing ≥90% cure rates have been proposed including sequential therapy, concomitant quadruple therapy, hybrid (dual-concomitant) therapy, and bismuth-containing quadruple therapy. These treatments are likely to represent the recommended first-line treatments in the near future. In the present paper, we are considering a series of critical issues regarding currently available means and approaches for the management of H. pylori infection. Clinical needs and realistic endpoints are taken into account. Furthermore, emerging strategies for the eradication of H. pylori and the existing evidence of their clinical validation and widespread applicability are discussed.
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Manyi-Loh CE, Clarke AM, Ndip RN. Detection of phytoconstituents in column fractions of n-hexane extract of Goldcrest honey exhibiting anti-Helicobacter pylori activity. Arch Med Res 2012; 43:197-204. [PMID: 22560982 DOI: 10.1016/j.arcmed.2012.04.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2011] [Accepted: 04/16/2012] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND AIMS Alternative therapy for Helicobacter pylori eradication from natural products is gaining much attention. This study sought to isolate and characterize the fraction responsible for the antibacterial activity in Goldcrest (GC) n-hexane extract. METHODS Thin-layer chromatography (TLC) of the extract was carried out on Silica gel plates to determine the presence of chemical compounds, which were separated and partially purified by column chromatography. The obtained fractions GCCL, GCF2, GCF3 and GCF4 were tested for anti-H. pylori activity using the broth microdilution method. Volatile compounds in the active fractions were identified by gas chromatography-mass spectrometry (GC-MS) analysis. MINITAB was used for statistical analysis at 95% confidence interval. RESULTS The best antibacterial activity was exhibited by GCF3 (5 mg/mL), which was composed of many compounds with known antimicrobial and antioxidant properties. A total of 16 volatile compounds were identified from fractions GCF2, GCF3 and GCF4 into the following families; alcohol, ketone, aliphatic acid, benzene compound, hydrocarbon, furan and pyran derivatives. CONCLUSIONS The demonstration of antibacterial activity by the column fractions of GC n-hexane extract may provide new lead molecules that could serve as selective agents for H. pylori chemotherapy and control.
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Affiliation(s)
- Christy E Manyi-Loh
- Microbial Pathogenicity and Molecular Epidemiology Research Group, Department of Biochemistry and Microbiology, Faculty of Science and Agriculture, University of Fort Hare, Alice, South Africa
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Monno R, Giorgio F, Carmine P, Soleo L, Cinquepalmi V, Ierardi E. Helicobacter pylori clarithromycin resistance detected by Etest and TaqMan real-time polymerase chain reaction: a comparative study. APMIS 2012; 120:712-7. [PMID: 22882260 DOI: 10.1111/j.1600-0463.2012.02896.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2011] [Accepted: 02/06/2012] [Indexed: 12/17/2022]
Abstract
The aim of the work was to compare H. pylori clarithromycin-resistance according two methods. Etest was performed on H. pylori isolated from gastric biopsy samples. TaqMan Real-Time-PCR (RT-PCR) was performed on paraffin-embedded gastric biopsy samples of the same patients. Forty-seven out of 88 strains were resistant to clarithromycin by Etest, whereas RT-PCR detected this resistance on paraffin-embedded specimens of 50 patients. RT-PCR performed on paraffin-embedded biopsy specimens of 47 patients infected with H. pylori resistant to clarithromycin as detected by Etest, revealed the presence of a resistant strain only in 40 samples. RT-PCR performed on samples of 41 patients harbouring clarithromycin-susceptible H. pylori strains showed the presence of 31 susceptible and 10 resistant strains. RT-PCR detected 18 cases with heteroresistant status. The difference between the two tests in detecting clarithromycin-resistance was not statistically significant even if RT-PCR detected more resistant cases. The genotyping resistance on paraffin-embedded gastric biopsy specimens may be used to establish resistance to clarithromycin before the treatment when culture and susceptibility testing are not available. In case of failure of an empirical clarithromycin-based triple antimicrobial treatment, RT-PCR performed on paraffin-embedded biopsy sample will establish the primary resistance to clarithromycin. In addition, this test can be useful for epidemiological investigation as well as for monitoring the evolution of clarithromycin resistance along the time.
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Affiliation(s)
- Rosa Monno
- Department of Odontostomatology and Surgery, University of Bari, Italy.
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Tursi A, Elisei W, Giorgetti G, Picchio M, Brandimarte G. Efficacy, Tolerability, and Factors Affecting the Efficacy of the Sequential Therapy in Curing Helicobacter Pylori Infection in Clinical Setting. J Investig Med 2011; 59:917-920. [DOI: 10.2310/jim.0b013e318217605f] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Abstract
Background Sequential therapy is currently suggested as first-line therapy in curing Helicobacter pylori infection, but results coming from its use in clinical practice are scarce. We evaluated the efficacy of this therapy regimen in our current clinical practice. Methods A retrospective study was conducted on 437 consecutive dyspeptic patients with proven H. pylori infection. Patients received a 10-day sequential therapy with proton pump inhibitor (PPI) plus amoxicillin 1 g for the first 5 days, followed by PPI, clarithromycin 500 mg, and tinidazole 500 mg for the remaining 5 days (all twice daily) plus PPI every day for further 4 weeks in case of active peptic ulcer or severe gastritis detected at endoscopy. One month after conclusion of therapy, endoscopy was performed in those patients for whom the examinations were clinically relevant. The remaining patients were checked by 13C-urea breath test. Results Three-hundred ninety-eight patients (91.08%; 95% confidence interval [CI], 87.91%-93.50%) were fully compliant, 19 patients (4.35%; 95% CI, 2.71%-6.83%) took less than 80% of the prescribed drugs, 11 patients (2.52%; 95% CI, 1.33%-4.60%) were withdrawn because of side effects, and 9 patients (2.06%; 95% CI, 1.01%-4.01%) were lost to follow-up. The H. pylori eradication was obtained in 395 (90.39%, 95% C.I. 87.14% to 92.91%) of 437 and in 362 of 437 (82.84%, 95% C.I. 78.90% to 86.19%) as per-protocol and intention-to-treat analyses, respectively. Conclusions Sequential regimen seems to be a valid therapeutic strategy for the management of H. pylori infection in clinical practice.
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Affiliation(s)
- Antonio Tursi
- Gastroenterology Service, ASL BAT, Andria (BAT), Albano Laziale
| | - Walter Elisei
- Division of Gastroenterology, ASL Roma H, Albano Laziale
| | | | - Marcello Picchio
- Division of General Surgery, “C. Colombo” Hospital, ASL RMH, Velletri, Rome, Italy
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