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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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2
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He XJ, Zeng XP, Jiang CS, Liu G, Li DZ, Wang W. Efficacy and Safety of Antofloxacin-Based Triple Therapy for Helicobacter pylori Eradication Failure in China. Dig Dis Sci 2022; 67:208-215. [PMID: 33559090 DOI: 10.1007/s10620-021-06856-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 01/17/2021] [Indexed: 02/08/2023]
Abstract
AIMS Quinolone-containing triple therapy has been considered as the second-line therapy for eradication of Helicobacter pylori (H. pylori). At present, there are no data to show the efficacy and safety of antofloxacin-based rescue therapy for the eradication of H. pylori, and this pilot clinical trial was designed. METHODS A total of 196 patients who failed H. pylori eradication using the clarithromycin-based or metronidazole-based triple or bismuth quadruple therapy were randomly allocated to one of the following rescue eradication therapy groups: AEA group (antofloxacin 200 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days, or LEA group (levofloxacin 500 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days. The minimal inhibitory concentrations were tested by the E-test method. The gyrA mutation was analyzed by sequencing. Follow-up 13/14C-urea breath test was examined at 1 month after discontinuation. RESULTS A total of 178 eligible patients were included in this study. The eradication rate was significantly higher in AEA group than in LEA group according to both ITT (87.6% vs. 68.5%; P = 0.002) and PP analyses (90.7% vs. 70.1%; P = 0.001). ITT analyses indicated that the eradication rate was significantly higher in AEA group than in LEA group with Asn87 mutation (78.9% vs. 31.3%; P = 0.005) and levofloxacin-resistant strains (76.9% vs. 44.2%; P = 0.003). Two groups exhibited similar adverse event rates (AEA 14.6% vs. LEA 20.2%, P = 0.323). CONCLUSIONS The findings showed that antofloxacin may be a promising candidate in rescue therapy for H. pylori eradication failure in China.
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Affiliation(s)
- Xiao-Jian He
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, 156 North Road of West No.2 Ring, Fuzhou, 350025, China
- Fuzhou General Clinical Medical College, Fujian Medical University, Fuzhou, China
- Oriental Hospital Affiliated To Xiamen University, Fuzhou, China
| | - Xiang-Peng Zeng
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, 156 North Road of West No.2 Ring, Fuzhou, 350025, China
- Fuzhou General Clinical Medical College, Fujian Medical University, Fuzhou, China
- Oriental Hospital Affiliated To Xiamen University, Fuzhou, China
| | - Chuan-Shen Jiang
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, 156 North Road of West No.2 Ring, Fuzhou, 350025, China
- Fuzhou General Clinical Medical College, Fujian Medical University, Fuzhou, China
- Oriental Hospital Affiliated To Xiamen University, Fuzhou, China
| | - Gang Liu
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, 156 North Road of West No.2 Ring, Fuzhou, 350025, China
- Fuzhou General Clinical Medical College, Fujian Medical University, Fuzhou, China
- Oriental Hospital Affiliated To Xiamen University, Fuzhou, China
| | - Da-Zhou Li
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, 156 North Road of West No.2 Ring, Fuzhou, 350025, China
- Fuzhou General Clinical Medical College, Fujian Medical University, Fuzhou, China
- Oriental Hospital Affiliated To Xiamen University, Fuzhou, China
| | - Wen Wang
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, 156 North Road of West No.2 Ring, Fuzhou, 350025, China.
- Fuzhou General Clinical Medical College, Fujian Medical University, Fuzhou, China.
- Oriental Hospital Affiliated To Xiamen University, Fuzhou, China.
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3
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Vermeulen H, Coenen S, Hens N, Bruyndonckx R. Impact of changing reimbursement criteria on the use of fluoroquinolones in Belgium. J Antimicrob Chemother 2021; 76:2725-2732. [PMID: 34374778 PMCID: PMC8446932 DOI: 10.1093/jac/dkab255] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 06/22/2021] [Indexed: 11/14/2022] Open
Abstract
Objectives The criteria for the reimbursement of fluoroquinolones changed in Belgium on 1 May 2018. This study aims to quantify the difference in fluoroquinolone use after this change, and to assess the timing and persistence of this effect, both in terms of total reimbursed fluoroquinolone use and its relative proportion. Methods Longitudinal reimbursement data on fluoroquinolone use in the Belgian community from January 2017 to November 2018 were analysed to identify a change in reimbursed fluoroquinolone use expressed in DDD per 1000 inhabitants per day (DID), using a set of non-linear mixed models including change-points. In addition, longitudinal data on the relative proportion of prescribed fluoroquinolones from January 2017 to December 2018 were analysed to identify a change in the relative proportion of prescribed fluoroquinolones using generalized estimation equations including change-points. Results Fluoroquinolone use dropped significantly immediately after the change in reimbursement criteria, from 2.21 DID (95% CI: 2.03–2.38) to 0.52 DID (95% CI: 0.48–0.56) and from 9.14% (95% CI: 8.75%–9.56%) to 6.52% (95% CI: 6.04%–7.04%). The observed decrease in fluoroquinolone use persisted over time. Conclusions While fluoroquinolone use was still above the target of 5% after the change in reimbursement criteria, its implementation helped to lower fluoroquinolone use in Belgium.
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Affiliation(s)
- Helene Vermeulen
- Interuniversity Institute for Biostatistics and statistical Bioinformatics (I-BIOSTAT), Data Science Institute (DSI), Hasselt University, Hasselt, Belgium
| | - Samuel Coenen
- Laboratory of Medical Microbiology (LMM), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.,Department of Family Medicine and Population Health (FAMPOP), University of Antwerp, Antwerp, Belgium
| | - Niel Hens
- Interuniversity Institute for Biostatistics and statistical Bioinformatics (I-BIOSTAT), Data Science Institute (DSI), Hasselt University, Hasselt, Belgium.,Department of Family Medicine and Population Health (FAMPOP), University of Antwerp, Antwerp, Belgium.,Centre for Health Economic Research and Modelling Infectious Diseases, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium
| | - Robin Bruyndonckx
- Interuniversity Institute for Biostatistics and statistical Bioinformatics (I-BIOSTAT), Data Science Institute (DSI), Hasselt University, Hasselt, Belgium.,Laboratory of Medical Microbiology (LMM), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium
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4
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González-Hormazábal P, Arenas A, Serrano C, Pizarro M, Fuentes-López E, Arnold J, Berger Z, Musleh M, Valladares H, Lanzarini E, Jara L, Castro VG, Camargo MC, Riquelme A. Prevalence of Helicobacter pylori Antimicrobial Resistance Among Chilean Patients. Arch Med Res 2021; 52:529-534. [PMID: 33583603 DOI: 10.1016/j.arcmed.2021.01.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 12/16/2020] [Accepted: 01/21/2021] [Indexed: 02/07/2023]
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Nkuize M, Vanderpas J, Buset M, Gomez-Galdon M, Delforge M, Miendje-Deyi VY, Muls V, De Wit S. Primary antibiotic resistance of Helicobacter pylori isolates is twofold more frequent in HIV-positive than HIV-negative individuals: A descriptive observational study. Microbiologyopen 2021; 10:e1184. [PMID: 34180600 PMCID: PMC8166256 DOI: 10.1002/mbo3.1184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 03/05/2021] [Accepted: 03/23/2021] [Indexed: 11/11/2022] Open
Abstract
The antimicrobial susceptibility of Helicobacter pylori strains isolated from HIV-positive individuals is not well characterized. This study aimed to measure the prevalence and long-term trends associated with primary H. pylori antibiotic resistance, evaluate correlations with antibiotic consumption, and compare predictors for H. pylori antibiotic resistance between HIV-positive and HIV-negative individuals. In this longitudinal registry study, we evaluated consecutive adults with and without HIV infection, naïve to H. pylori treatment, who underwent upper gastrointestinal endoscopy and had a positive H. pylori culture, with susceptibility testing available, between 2004 and 2015. Outpatient antibiotic consumption data were based on nationwide aggregated numbers. H. pylori was isolated from gastric biopsies of 3008/8321 patients, 181/477 (37.9%) were HIV-positive and 2827/7844 (36.0%) HIV-negative. Overall cohort mean prevalence of H. pylori primary antibiotic resistance was 11.1% for clarithromycin, 17.8% levofloxacin, and 39.4% metronidazole. The prevalence of H. pylori primary resistance was significantly higher for these three drugs in HIV-positive individuals across the study period. Linear regression showed that the prevalence of clarithromycin and levofloxacin resistance correlated with the country aggregate daily dose consumption of macrolides and quinolones, respectively. Multivariable regression analysis showed that HIV infection is a strong independent risk factor for multiple H. pylori antibiotic resistance. In summary, HIV infection is a risk factor for carrying multi-resistant H. pylori strains and this is correlated with antibiotic consumption. Empirical therapies should be avoided in HIV-positive individuals. These data highlight the need to implement ongoing monitoring of H. pylori antimicrobial susceptibility among HIV-positive individuals. The study is registered at ISRCTN registry, number 13466428: https://www.isrctn.com/ISRCTN13466428.
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Affiliation(s)
- Marcel Nkuize
- Department of Gastroenterology and Hepatology, CHU Saint Pierre Université Libre de Bruxelles, Bruxelles, Belgium
| | - Jean Vanderpas
- Department of Hospital Hygiene & Infection Control, CHU Saint Pierre Université Libre de Bruxelles, Bruxelles, Belgium
| | - Michel Buset
- Department of Gastroenterology and Hepatology, CHU Saint Pierre Université Libre de Bruxelles, Bruxelles, Belgium.,Department of Gastroenterology and Hepatology, Delta Hospital, CHIREC, Bruxelles, Belgium
| | - Maria Gomez-Galdon
- Department of Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Marc Delforge
- Department of Infectious Diseases, CHU Saint Pierre Université Libre de Bruxelles, Bruxelles, Belgium
| | - Véronique Yvette Miendje-Deyi
- Department of Microbiology-LHUB, Pôle Hospitalier Universitaire de Bruxelles, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Vinciane Muls
- Department of Gastroenterology and Hepatology, CHU Saint Pierre Université Libre de Bruxelles, Bruxelles, Belgium
| | - Stéphane De Wit
- Department of Infectious Diseases, CHU Saint Pierre Université Libre de Bruxelles, Bruxelles, Belgium
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Salehi N, Attaran B, Eskini N, Esmaeili M, Sharifirad A, Sadeghi M, Mohammadi M. New insights into resistance of Helicobacter pylori against third- and fourth-generation fluoroquinolones: A molecular docking study of prevalent GyrA mutations. Helicobacter 2019; 24:e12628. [PMID: 31282059 DOI: 10.1111/hel.12628] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 05/04/2019] [Accepted: 05/28/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND Fluoroquinolones hinder bacterial DNA replication by inhibiting DNA gyrase. However, mutations, in the QRDR segment of its A subunit (GyrA), cause antibiotic resistance. Here, the interactions of levofloxacin (LVX), gemifloxacin (GXN), and moxifloxacin (MXN) with Helicobacter pylori GyrA, in LVX-resistant vs -sensitive strains, were studied. METHODS Levoflixacin-sensitive (n = 4) and -resistant (n = 9) H pylori strains, randomly selected from another antibiotic susceptibility study, underwent PCR amplification of gyrA gene, spanning the QRDR segment. The amplified gene fragments were sequenced and aligned. The homology model of H pylori GyrA was built based on that of Escherichia coli, and energy minimization was done. The interaction patterns of LVX, GXN, and MXN with GyrA were analyzed via molecular docking studies. RESULTS Sequence alignment of the 13 studied strains, created 5 categories of strains: (A) wild type-like (H pylori ATCC26695), (B) N87K-only, (C) D91N-only, (D) N87K + V94L, and (E) D91N + A97V mutations. The minimum inhibitory concentrations (MIC) for LVX-sensitive (category A) and -resistant (categories B-E) strains were <1 mg/L and ≥32 mg/L, respectively. The binding mode of GyrA in category A with LVX identified G35/N87/Y90/D91/V94/G114/S115/I116/D117/G118/D119, as key residues, some residing outside the QRDR segment. Category B strains lost only one interaction (G35), which led to elevated binding free energy (∆G) and full LVX resistance. Categories C-E lost more contacts, with higher ∆G and again full LVX resistance. GXN bound to GyrA of categories A and B via a different set of key residues, while MXN retained the lost contact (G35) in LVX-resistant, category B strains. CONCLUSION Using molecular docking tools, we identified the key residues responsible for interaction of GyrA with LVX, GXN, and MXN. In the presence of N87K-only mutation, the loss of one of these contacts (ie, G35) led to full LVX resistance. Yet, GXN and MXN overcame this mutation, by retaining all key contacts with GyrA.
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Affiliation(s)
- Najmeh Salehi
- Department of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
| | - Bahareh Attaran
- HPGC Research Group, Department of Medical Biotechnology, Pasteur Institute of Iran, Tehran, Iran.,Department of Microbiology, Faculty of Biology, Alzahra University, Tehran, Iran
| | - Negin Eskini
- HPGC Research Group, Department of Medical Biotechnology, Pasteur Institute of Iran, Tehran, Iran
| | - Maryam Esmaeili
- HPGC Research Group, Department of Medical Biotechnology, Pasteur Institute of Iran, Tehran, Iran
| | - Atefeh Sharifirad
- HPGC Research Group, Department of Medical Biotechnology, Pasteur Institute of Iran, Tehran, Iran
| | - Mehdi Sadeghi
- National Institute for Genetic Engineering and Biotechnology, Tehran, Iran
| | - Marjan Mohammadi
- HPGC Research Group, Department of Medical Biotechnology, Pasteur Institute of Iran, Tehran, Iran
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Genetic Determinants and Prediction of Antibiotic Resistance Phenotypes in Helicobacter pylori. J Clin Med 2019; 8:jcm8010053. [PMID: 30621024 PMCID: PMC6351930 DOI: 10.3390/jcm8010053] [Citation(s) in RCA: 81] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 12/29/2018] [Accepted: 12/31/2018] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori is a major human pathogen. Diagnosis of H. pylori infection and determination of its antibiotic susceptibility still mainly rely on culture and phenotypic drug susceptibility testing (DST) that is time-consuming and laborious. Whole genome sequencing (WGS) has recently emerged in medical microbiology as a diagnostic tool for reliable drug resistance prediction in bacterial pathogens. The aim of this study was to compare phenotypic DST results with the predictions based on the presence of genetic determinants identified in the H. pylori genome using WGS. Phenotypic resistance to clarithromycin, metronidazole, tetracycline, levofloxacin, and rifampicin was determined in 140 clinical H. pylori isolates by E-Test®, and the occurrence of certain single nucleotide polymorphisms (SNPs) in target genes was determined by WGS. Overall, there was a high congruence of >99% between phenotypic DST results for clarithromycin, levofloxacin, and rifampicin and SNPs identified in the 23S rRNA, gyrA, and rpoB gene. However, it was not possible to infer a resistance phenotype for metronidazole based on the occurrence of distinct SNPs in frxA and rdxA. All 140 H. pylori isolates analysed in this study were susceptible to tetracycline, which was in accordance with the absence of double or triple nucleotide substitutions in the 16S rRNA gene.
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8
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Simultaneous detection of human CYP2C19 polymorphisms and antibiotic resistance of Helicobacter pylori using a personalised diagnosis kit. J Glob Antimicrob Resist 2018; 13:174-179. [PMID: 29444465 DOI: 10.1016/j.jgar.2017.12.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 12/22/2017] [Accepted: 12/30/2017] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVES A personalised diagnosis kit for Helicobacter pylori that employs visual gene chip technology for the simultaneous detection of CYP2C19 polymorphisms and clarithromycin/levofloxacin antibiotic resistance was evaluated. METHODS Gastric antrum mucosa biopsy specimens of 394 patients were tested using the kit. DNA sequencing and antibiotic susceptibility testing of the H. pylori were also performed. RESULTS In total, 267 (67.8%) of the 394 specimens were positive for H. pylori using the kit and DNA sequencing, and 136 (34.5%) were positive by culturing. For human CYP2C19 and the bacterial 23S rRNA and gyrA genes, the concordance rates were 92.4% (364/394), 96.6% (258/267) and 97.0% (259/267) between the kit and DNA sequencing results, respectively. For clarithromycin and levofloxacin resistance, the concordance rates were 90.4% (123/136) and 81.6% (111/136) between the kit and antibiotic susceptibility testing results. CONCLUSIONS The personalised diagnosis kit for H. pylori provides useful information for the choice of proton pump inhibitor and antibiotic in combination therapy.
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9
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Martins GM, Sanches BSF, Moretzsohn LD, Lima KS, Cota BDCV, Coelho LGV. MOLECULAR DETECTION OF CLARITHROMYCIN AND FLUOROQUINOLONES RESISTANCE IN HELICOBACTER PYLORI INFECTION, DIRECTLY APPLIED TO GASTRIC BIOPSIES, IN AN URBAN BRAZILIAN POPULATION. ARQUIVOS DE GASTROENTEROLOGIA 2017; 53:113-7. [PMID: 27305419 DOI: 10.1590/s0004-28032016000200012] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Accepted: 02/01/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND - Antimicrobial resistance is the major factor leading to eradication failure in H. pylori treatment. Molecular tests are useful to detect genetic mutations predictive of clarithromycin and fluoroquinolones resistance. Knowledge of the local prevalence rate of resistance is important to define the best recommended treatment. OBJECTIVE - To assess the prevalence of primary resistance of H. pylori to clarithromycin and fluoroquinolones, using a molecular test, in a Southeastern urban Brazilian population. METHODS - A total of 72 H. pylori seropositive patients [65% female, mean age 39 (19-73) years] never treated before for this infection were studied. All patients underwent gastroscopy in addition to antrum and corpus biopsies and molecular test GenoType HelicoDR (Hain Life Science, Germany) to detect H. pylori and point mutations in genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from biopsy samples, a multiplex amplification with biotinylated primers and a reverse hybridization. The most frequent point mutations involved in resistance to the two antibiotics were evaluated. RESULTS - Resistance to clarithromycin was detected in nine (12.5%) patients and to fluoroquinolones in eight (11.1%) patients. The point mutation A2147G was the most common (77.8%) among resistant strains to clarithromycin. In 50% of the resistant strains to fluoroquinolones, the mutant codon couldn't be identified. CONCLUSION - The resistance rates to clarithromycin and fluorquinolones in a large urban population in the Southeast of Brazil were acceptable, suggesting that these drugs remain appropriate options to first and second-line of H. pylori treatment. The molecular test represents an adequate diagnostic tool for monitoring H. pylori resistance.
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Affiliation(s)
- Gustavo Miranda Martins
- Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil., Universidade Federal de Minas Gerais, Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Belo Horizonte MG , Brazil
| | - Bruno Squárcio Fernandes Sanches
- Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil., Universidade Federal de Minas Gerais, Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Belo Horizonte MG , Brazil
| | - Luciana Dias Moretzsohn
- Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil., Universidade Federal de Minas Gerais, Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Belo Horizonte MG , Brazil
| | - Karine Sampaio Lima
- Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil., Universidade Federal de Minas Gerais, Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Belo Horizonte MG , Brazil
| | - Bianca Della Croce V Cota
- Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil., Universidade Federal de Minas Gerais, Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Belo Horizonte MG , Brazil
| | - Luiz Gonzaga Vaz Coelho
- Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil., Universidade Federal de Minas Gerais, Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Belo Horizonte MG , Brazil
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10
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Abstract
In current clinical practice, there is no optimal empirical therapy for Helicobacter pylori (H. pylori) infection and there is a progressive decrease in the efficiency of classical eradication therapy (ET) regimens. The variability in the efficiency of ET in a specific patient is largely due to the heterogeneous molecular genetic mechanisms underlying the resistance of the microorganism to the components of the treatment regimens. The basis of the mechanisms for antibiotic resistance in H. pylori is mainly the point mutations in some genes, which determine alterations in the mechanisms of action of drugs, such as clarithromycin (domain V of 23S rRNA), metronidazole (rdxA, frxA), amoxicillin (pbp1A), tetracycline (16S rRNA), and levofloxacin (gyrA). The predictors of resistance to ET are also the CagA-negative status of the microorganism and the presence of the vacA s2 allele. There are a number of host genetic determinants (the CYP2C19 genotype (*1/*1, *1/*17, *17/*17) and the MDR1 3435 T/T genotype (in an Asian population)) that reduce the efficiency of ET, by altering the pharmacokinetics of proton pump inhibitors. In addition, the IL-1β-511 C/C polymorphism that affects gastric acid secretion is a predictor of the inefficiency of ET.
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Affiliation(s)
- I V Maev
- A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
| | - D N Andreev
- A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
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11
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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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Chen PY, Wu MS, Chen CY, Bair MJ, Chou CK, Lin JT, Liou JM. Systematic review with meta-analysis: the efficacy of levofloxacin triple therapy as the first- or second-line treatments of Helicobacter pylori infection. Aliment Pharmacol Ther 2016; 44:427-37. [PMID: 27363687 DOI: 10.1111/apt.13712] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2016] [Revised: 04/27/2016] [Accepted: 06/08/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Levofloxacin triple therapy has been used for the first-line and second-line treatment of Helicobacter pylori infection for more than 10 years. AIMS To systematically review the efficacy of levofloxacin triple therapy in the first- and second-line treatment, and to assess the time trend and factors that might affect its efficacy. METHODS Prospective trials reporting the efficacy of levofloxacin triple therapy in either the first-line or second-line treatment of H. pylori infection in adults were searched from the PubMed and Cochrane database from January 2000 to September 2015. Meta-analysis was performed to calculate the cumulative eradication rate and the efficacies in subgroups. RESULTS Of the 322 articles identified, a total of 4574 patients from 41 trials, including 16 trials in the first-line treatment and 25 trials in the second-line treatment were eligible for analysis. The cumulative eradication rate was 77.3% (95% confidence intervals, CI: 74.7-79.6) and was 80.7% (95% CI 77.1-83.7) in the first-line treatment and 74.5% (95% CI: 70.9-77.8) in the second-line treatment. The efficacies of levofloxacin triple therapy before 2008, between 2009 and 2011, and after 2012 were 77.4%, 79.6% and 74.8% respectively. The eradication rate was higher when levofloxacin was given once daily (80.6%, 95% CI: 77.1-83.7) than twice daily (73.6%, 95% CI: 69.7-77.2). The efficacy was significantly higher in levofloxacin-susceptible strains than resistant strains (81.1% vs. 36.3%, risk ratio 2.18, 95% CI: 1.6-3, P < 0.001). CONCLUSION The efficacy of levofloxacin triple therapy has been lower than 80% in many countries and it is not recommended when the levofloxacin resistance is higher than 5-10%.
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Affiliation(s)
- P-Y Chen
- Department of Internal Medicine, Ditmanson Medication Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan
| | - M-S Wu
- Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - C-Y Chen
- Department of Internal Medicine, Ditmanson Medication Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan
| | - M-J Bair
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taiwan
- Department of Nursing, Meiho University, Pingtung, Taiwan
| | - C-K Chou
- Department of Internal Medicine, Ditmanson Medication Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan
| | - J-T Lin
- Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
- School of Medicine and Big Data Research Centre, Fu Jen Catholic University, New Taipei City, Taiwan
| | - J-M Liou
- Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
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Ang TL, Fock KM, Ang D, Kwek ABE, Teo EK, Dhamodaran S. The Changing Profile of Helicobacter pylori Antibiotic Resistance in Singapore: A 15-Year Study. Helicobacter 2016; 21:261-5. [PMID: 26774006 DOI: 10.1111/hel.12291] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Antibiotic resistance is an important cause of H. pylori treatment failure. This study aimed to examine the change in H. pylori antibiotic resistance profile in Singapore over the course of 15 years. MATERIALS AND METHODS The study period was from 2000 to 2014. Gastric mucosal biopsies obtained from H. pylori-positive patients were cultured. Antibiotic susceptibility to metronidazole, clarithromycin, levofloxacin, tetracycline, and amoxicillin was tested. The change in resistance rates over time was analyzed. RESULTS A total of 708 H. pylori isolates were cultured. There was a significant increase in resistance rates for metronidazole (2000-2002: 24.8%; 2012-2014: 48.2%; p < .001), clarithromycin (2000-2002: 7.9%; 2012-2014: 17.1%; p = .022), and levofloxacin (2000-2002: 5%; 2012-2014: 14.7%; p = .007). The resistance rates for tetracycline (2000-2002: 5%; 2012-2014: 7.6%) and amoxicillin (2000-2002: 3%; 2012-2014: 4.4%) remained stable. Increase in dual (2000-2002: 6.9%; 2012-2014: 9.4%; p = .479) and triple antibiotic resistance rates (2000-2002: 0; 2012-2014: 7.6%; p < .001) were observed. Overall, the most common dual and triple resistance patterns were metronidazole/clarithromycin (4.4%) and metronidazole/clarithromycin/levofloxacin (1.8%), respectively. CONCLUSIONS Over 15 years, H. pylori resistance rates to metronidazole, clarithromycin and levofloxacin had increased. There was increased resistance to multiple antibiotics.
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Affiliation(s)
- Tiing Leong Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore, Singapore
| | - Kwong Ming Fock
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore, Singapore
| | - Daphne Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore, Singapore
| | - Andrew Boon Eu Kwek
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore, Singapore
| | - Eng Kiong Teo
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore, Singapore
| | - Subbiah Dhamodaran
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore, Singapore
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Trespalacios-Rangél AA, Otero W, Arévalo-Galvis A, Poutou-Piñales RA, Rimbara E, Graham DY. Surveillance of Levofloxacin Resistance in Helicobacter pylori Isolates in Bogotá-Colombia (2009-2014). PLoS One 2016; 11:e0160007. [PMID: 27454429 PMCID: PMC4959775 DOI: 10.1371/journal.pone.0160007] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Accepted: 07/12/2016] [Indexed: 12/20/2022] Open
Abstract
Increased resistance of Helicobacter pylori to clarithromycin and metronidazole has resulted in recommendation to substitute fluoroquinolones for eradication therapy. The aims of the study were to determine the prevalence and changes in primary levofloxacin resistance related to H. pylori gyrA sequences. The study utilized H. pylori strains isolated from patients undergoing gastroscopy in Bogotá, Colombia from 2009 to 2014. Levofloxacin susceptibility was assessed by agar dilution. Mutations in gyrA sequences affecting the quinolone resistance-determining region (QRDR) were evaluated by direct sequencing. Overall, the mean prevalence of primary levofloxacin resistance was 18.2% (80 of 439 samples). Resistance increased from 11.8% (12/102) in 2009 to 27.3% (21/77) in 2014 (p = 0.001). gyrA mutations in levofloxacin resistant strains were present in QRDR positions 87 and 91. The most common mutation was N87I (43.8%, 35/80) followed by D91N (28.8%, 23/80) and N87K (11.3%, 9/80). Levofloxacin resistance increased markedly in Colombia during the six-year study period. Primary levofloxacin resistance was most often mediated by point mutations in gyrA, with N87I being the most common QRDR mutation related to levofloxacin resistance.
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Affiliation(s)
- Alba A. Trespalacios-Rangél
- Grupo de Enfermedades Infecciosas, Departamento de Microbiología, Pontificia Universidad Javeriana, Bogotá, D.C, Colombia
- * E-mail:
| | - William Otero
- Unidad de Gastroenterología, Universidad Nacional de Colombia, Bogotá, D.C, Colombia
| | - Azucena Arévalo-Galvis
- Grupo de Enfermedades Infecciosas, Departamento de Microbiología, Pontificia Universidad Javeriana, Bogotá, D.C, Colombia
| | - Raúl A. Poutou-Piñales
- Grupo de Biotecnología Ambiental e Industrial (GBAI). Departamento de Microbiología, Pontificia Universidad Javeriana, Bogotá, D.C, Colombia
| | - Emiko Rimbara
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Houston TX, United States of America
- Baylor College of Medicine, Houston TX, United States of America
| | - David Y. Graham
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Houston TX, United States of America
- Baylor College of Medicine, Houston TX, United States of America
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Mégraud F, Bénéjat L, Ontsira Ngoyi EN, Lehours P. Molecular Approaches to Identify Helicobacter pylori Antimicrobial Resistance. Gastroenterol Clin North Am 2015; 44:577-96. [PMID: 26314669 DOI: 10.1016/j.gtc.2015.05.002] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Antimicrobial susceptibility testing is needed to adapt Helicobacter pylori treatment to obtain the best results. Beside the standard phenotypic methods, molecular methods are increasingly used. The value of these molecular tests is that they are quick, independent of the transport conditions, easy to standardize, and commercial kits are available. In this article, these methods are reviewed, focusing on the determination of H pylori resistance to macrolides and fluoroquinolones, and mentioning also the methods used for tetracycline and rifampin.
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Affiliation(s)
- Francis Mégraud
- Bacteriology Laboratory, INSERM U853, University of Bordeaux, Bordeaux F-33000, France.
| | - Lucie Bénéjat
- Bacteriology Laboratory, INSERM U853, University of Bordeaux, Bordeaux F-33000, France
| | | | - Philippe Lehours
- Bacteriology Laboratory, INSERM U853, University of Bordeaux, Bordeaux F-33000, France
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Gisbert JP, Romano M, Molina-Infante J, Lucendo AJ, Medina E, Modolell I, Rodríguez-Tellez M, Gomez B, Barrio J, Perona M, Ortuño J, Ariño I, Domínguez-Muñoz JE, Perez-Aisa Á, Bermejo F, Domínguez JL, Almela P, Gomez-Camarero J, Millastre J, Martin-Noguerol E, Gravina AG, Martorano M, Miranda A, Federico A, Fernandez-Bermejo M, Angueira T, Ferrer-Barcelo L, Fernández N, Marín AC, McNicholl AG. Two-week, high-dose proton pump inhibitor, moxifloxacin triple Helicobacter pylori therapy after failure of standard triple or non-bismuth quadruple treatments. Dig Liver Dis 2015; 47:108-13. [PMID: 25454706 DOI: 10.1016/j.dld.2014.10.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2014] [Revised: 09/01/2014] [Accepted: 10/12/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Aim was to evaluate the efficacy and tolerability of a moxifloxacin-containing second-line triple regimen in patients whose previous Helicobacter pylori eradication treatment failed. METHODS Prospective multicentre study including patients in whom a triple therapy or a non-bismuth-quadruple-therapy failed. Moxifloxacin (400mg qd), amoxicillin (1g bid), and esomeprazole (40 mg bid) were prescribed for 14 days. Eradication was confirmed by (13)C-urea-breath-test. Compliance was determined through questioning and recovery of empty medication envelopes. RESULTS 250 patients were consecutively included (mean age 48 ± 15 years, 11% with ulcer). Previous (failed) therapy included: standard triple (n = 179), sequential (n = 27), and concomitant (n = 44); 97% of patients took all medications, 4 were lost to follow-up. Intention-to-treat and per-protocol eradication rates were 82.4% (95% CI, 77-87%) and 85.7% (95% CI, 81-90%). Cure rates were similar independently of diagnosis (ulcer, 77%; dyspepsia, 82%) and previous treatment (standard triple, 83%; sequential, 89%; concomitant, 77%). At multivariate analysis, only age was associated with eradication (OR = 0.957; 95% CI, 0.933-0.981). Adverse events were reported in 25.2% of patients: diarrhoea (9.6%), abdominal pain (9.6%), and nausea (9.2%). CONCLUSION 14-day moxifloxacin-containing triple therapy is an effective and safe second-line strategy in patients whose previous standard triple therapy or non-bismuth quadruple (sequential or concomitant) therapy has failed, providing a simple alternative to bismuth quadruple regimen.
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Affiliation(s)
- Javier P Gisbert
- Univeristy Hospital La Princesa, Instituto de Investigación Sanitaria Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Spain.
| | - Marco Romano
- University Hospital, Seconda University of Naples, Naples, Italy
| | | | | | | | | | | | - Blas Gomez
- Hospital Quirón Sagrado Corazón, Seville, Spain
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Agnese Miranda
- University Hospital, Seconda University of Naples, Naples, Italy
| | | | | | | | | | | | - Alicia C Marín
- Univeristy Hospital La Princesa, Instituto de Investigación Sanitaria Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Spain
| | - Adrián G McNicholl
- Univeristy Hospital La Princesa, Instituto de Investigación Sanitaria Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Spain
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Papastergiou V, Georgopoulos SD, Karatapanis S. Treatment of Helicobacter pylori infection: meeting the challenge of antimicrobial resistance. World J Gastroenterol 2014; 20:9898-911. [PMID: 25110420 PMCID: PMC4123371 DOI: 10.3748/wjg.v20.i29.9898] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2013] [Revised: 01/27/2014] [Accepted: 03/12/2014] [Indexed: 02/06/2023] Open
Abstract
Treatment of Helicobacter pylori (H. pylori) infection is paramount for the management of prevalent gastrointestinal disorders including peptic ulcer disease and gastric cancer. Due to the wide increase in prevalence of H. pylori resistance to antibiotics, clarithromycin-based triple therapies are not any more suitable for unconditional empiric use, and should not be recommended, unless local resistance to this antibiotic is low (< 20%). Alternative strategies have been proposed to overcome the issue of increasing clarithromycin resistance, and some of them are already implemented in clinical practice. These comprise: (1) adoption of novel, more effective, empirical treatments: bismuth quadruple, sequential, non-bismuth quadruple (concomitant), dual-concomitant (hybrid), and levofloxacin-based regimens, the latter mainly designated as second-line/rescue options; (2) perspectives for a susceptibility-guided (tailored) therapeutic approach based on culture-free molecular testing methods; and (3) adjunct use of probiotics to improve eradication rates. The present article is aimed to provide a comprehensive overview of current and emerging strategies in the treatment of H. pylori infection, focusing on the challenge of antimicrobial resistance.
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18
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Talebi Bezmin Abadi A. Therapy of Helicobacter pylori: present medley and future prospective. BIOMED RESEARCH INTERNATIONAL 2014; 2014:124607. [PMID: 24800203 PMCID: PMC3988734 DOI: 10.1155/2014/124607] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Accepted: 03/16/2014] [Indexed: 12/19/2022]
Abstract
The increasing prevalence of antimicrobial resistance has warned clinicians to adopt new strategies for dealing with the H. pylori infection. The success of various therapeutic regimens has recently declined to unacceptable levels. To date, first line therapies (including concomitant therapy and hybrid therapy), second line therapies (including bismuth-containing quadruple therapy and levofloxacin-containing therapy), and third line therapy (culture-guided therapy) had been introduced. In the near future, treatment of H. pylori is entering into a completely new resistance era. In this setting, despite the recent progress, we may only be targeting the patients with problematic H. pylori. Local preference for antibiotic selection should be an inevitable article in each therapeutic regimen worldwide. Meanwhile, improving the patients' compliance protocols and observed side effects in suggested therapeutic regimens should be considered cautiously. The new strategies in treatment should be adopted based upon local resistance patterns, which requires physician's resistance about the recommended guidelines. Designing new therapeutic regimen, which contains most effective available antibiotics with less possible side effects and high patient compliance, represents a challenging task in treatment of H. pylori infections.
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Affiliation(s)
- Amin Talebi Bezmin Abadi
- Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
- Department of Medical Bacteriology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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19
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Furuta T, Sugimoto M, Kodaira C, Nishino M, Yamade M, Uotani T, Sahara S, Ichikawa H, Yamada T, Osawa S, Sugimoto K, Watanabe H, Umemura K. Sitafloxacin-based third-line rescue regimens for Helicobacter pylori infection in Japan. J Gastroenterol Hepatol 2014; 29:487-93. [PMID: 24224808 DOI: 10.1111/jgh.12442] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/25/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUNDS Quinolone-based regimens have been used as the rescue for eradication of Helicobacter pylori. Sitafloxacin is known to have low minimum inhibitory concentration for H. pylori. Here, we compared two sitafloxacin-based eradication regimens as rescue for the eradication of H. pylori. METHODS We attempted to eradicate H. pylori in 180 Japanese patients who had never failed in eradication of H. pylori with the triple proton pump inhibitor/amoxicillin/clarithromycin therapy (1st line) and the triple proton pump inhibitor/amoxicillin/metronidazole therapy (2nd line). They were assigned to either the triple therapy with rabeprazole 10 mg b.i.d./q.i.d., amoxicillin 500 mg q.i.d, and sitafloxacin 100 mg b.i.d. (RAS) for 1 or 2 weeks or the triple therapy with rabeprazole 10 mg b.i.d./q.i.d., metronidazole 250 mg b.i.d., and sitafloxacin 100 mg b.i.d. (RMS) for 1 or 2 weeks. Eradication was assessed via the (13) C-urea breath test and rapid urease test. RESULTS Intention-to-treat and per-protocol analyses of eradication rates were 84.1% (37/44) and 86.4% (37/43) with RAS for 1 week, 88.9% (40/45) and 90.9% (40/44) for RAS for 2 weeks, 90.9% (40/44) and 90.9% (40/44) for 1 week-RMS and 87.2% (41/47) and 91.1% (41/45) with RMS for 2 weeks. We noted no statistical significant differences in eradication rates among four regimens. CONCLUSION All of the above-described rescue regimens proved relatively equally useful in the eradication of H. pylori. Of them, RAS for 2 weeks and RMS for 1 or 2 weeks could attain the rescue eradication rates higher than 90% by per-protocol analysis.
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Affiliation(s)
- Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan
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Abstract
Helicobacter pylori (H. pylori) has been identified as the most important risk factor for chronic active gastritis and peptic ulcer disease. Resistance to antibiotics is increasing in H. pylori and is the main reason for failure of H. pylori eradication therapy. It is now widely accepted that resistance to fluoroquinolones (levofloxacin) is related with mutations of H. pylori gyrA gene. Molecular mechanisms of and detection methods for H. pylori resistance to levofloxacin have become the focus of current research. Therefore, study on H. pylori resistance to antibiotics is of great significance for eradication therapy of H. pylori infection.
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Furuta T, Sugimoto M, Yamade M, Uotani T, Sahara S, Ichikawa H, Kagami T, Yamada T, Osawa S, Sugimoto K, Watanabe H, Umemura K. Eradication of H. pylori infection in patients allergic to penicillin using triple therapy with a PPI, metronidazole and sitafloxacin. Intern Med 2014; 53:571-5. [PMID: 24633026 DOI: 10.2169/internalmedicine.53.1677] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Eradication of H. pylori in patients allergic to penicillin should be performed using regimens without penicillin derivatives. We treated a total of 28 patients allergic to penicillin with a proton pump inhibitor (PPI), metronidazole (250 mg bid) and sitafloxacin (100 mg bid) for one to two weeks. At four to eight weeks after the treatment, the patients underwent the [(13)C]-urea breath test. The overall eradication rate was 100.0%. Mild adverse events were observed. Triple therapy with a PPI, metronidazole and sitafloxacin is well tolerated and effective for the eradication of H. pylori in patients allergic to penicillin.
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Affiliation(s)
- Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Japan
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22
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Allele-Specific Polymerase Chain Reaction for Detection of Main gyrA Allelic Variants in Helicobacter pylori Strains. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2013. [DOI: 10.5812/archcid.19312] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Liao J, Zheng Q, Liang X, Zhang W, Sun Q, Liu W, Xiao S, Graham DY, Lu H. Effect of fluoroquinolone resistance on 14-day levofloxacin triple and triple plus bismuth quadruple therapy. Helicobacter 2013; 18:373-7. [PMID: 23581720 PMCID: PMC3974565 DOI: 10.1111/hel.12052] [Citation(s) in RCA: 82] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
OBJECTIVE Levofloxacin has been proposed to replace clarithromycin for Helicobacter pylori treatment. Seven- and 10-day fluoroquinolone triple therapies have generally failed to achieve cure rates of ≥90%, whereas 14-day therapy has achieved 95% success. The aim was to assess the efficacy and effect of fluoroquinolone resistance on 14-day levofloxacin-containing triple therapy with or without the addition of bismuth. DESIGN Helicobacter pylori-positive patients with functional dyspepsia or healed peptic ulcers were randomized to receive lansoprazole 30 mg b.i.d., amoxicillin 1000 mg b.i.d., and levofloxacin 500 mg daily with (B-LAL) or without (LAL) bismuth potassium citrate 220 mg b.i.d. for 14 days. Eradication was assessed by ¹³C-urea breath testing 4 weeks after completing treatment. Antimicrobial susceptibility was by the agar dilution method. Success was defined as PP success ≥90%. RESULTS A total of 152 of 161 patients (81 LAL and 80 B-LAL) enrolled completed treatment. The PP rates were 94.6% (70/74; 95% CI, 86.9-97.9%) with B-LAL and 85.9% (95% CI, 76.5-91.9%) with LAL (p = .07); the ITT eradication rates were 87.5% (95% CI, 78.5-93.1%) with B-LAL and 82.7% (95% CI, 73-89.4%) with LAL (p = .39). Levofloxacin resistance was present in 30.3%. Treatment success was excellent with susceptible strains (97.5%) versus resistant strains (70.6%) for B-LAL and 97.3% versus 37.5% for LAL, respectively. CONCLUSIONS Fourteen-day fluoroquinolone therapy was highly effective when fluoroquinolone resistance rates are <12%. The addition of bismuth maintained effectiveness with fluoroquinolone resistance as high as 25%.
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Affiliation(s)
- Jingxian Liao
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - Qing Zheng
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - Xiao Liang
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - Wei Zhang
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - Qinjuan Sun
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - Wenzhong Liu
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - Shudong Xiao
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - David Y. Graham
- Department of Medicine, Michael E. DeBakey VA Medical Center, Houston, TX, USA
| | - Hong Lu
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
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Vilaichone RK, Yamaoka Y, Shiota S, Ratanachu-ek T, Tshering L, Uchida T, Fujioka T, Mahachai V. Antibiotics resistance rate of Helicobacter pylori in Bhutan. World J Gastroenterol 2013; 19:5508-5512. [PMID: 24023494 PMCID: PMC3761104 DOI: 10.3748/wjg.v19.i33.5508] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2013] [Revised: 04/13/2013] [Accepted: 05/17/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To survey the antibiotic resistance pattern of Helicobacter pylori (H. pylori) strains isolated from Bhutanese population.
METHODS: We isolated 111 H. pylori strains from the gastric mucosa of H. pylori-infected patients in Bhutan in 2010. The Epsilometer test was used to determine the minimum inhibitory concentrations (MICs) of amoxicillin (AMX), clarithromycin (CLR), metronidazole (MNZ), levofloxacin (LVX), ciprofloxacin (CIP), and tetracycline (TET).
RESULTS: Nineteen of the isolated H. pylori strains were susceptible to all antibiotics tested. The isolated strains showed the highest rate of antibiotic resistance to MNZ (92/111, 82.9%). Among the 92 MNZ-resistant strains, 74 strains (80.4%) showed high-level resistance (MIC ≥ 256 μg/mL). Three strains were resistance to LVX (2.7%). These strains were also resistance to CIP. None of the strains showed resistance to CLR, AMX and TET.
CONCLUSION: CLR-based triple therapy is a more effective treatment approach over MNZ-based triple therapy for H. pylori infection in Bhutan.
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Wueppenhorst N, Stueger HP, Kist M, Glocker EO. High secondary resistance to quinolones in German Helicobacter pylori clinical isolates. J Antimicrob Chemother 2013; 68:1562-6. [PMID: 23463210 DOI: 10.1093/jac/dkt061] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES The aim of this study was to update data on levofloxacin/ciprofloxacin and triple resistance (resistance to metronidazole, clarithromycin and levofloxacin/ciprofloxacin) in Helicobacter pylori clinical isolates and to identify the impact of prior eradication therapies on their development. METHODS We tested the antimicrobial susceptibility to amoxicillin, metronidazole, clarithromycin, levofloxacin/ciprofloxacin, tetracycline and rifampicin of 5296 clinical H. pylori strains isolated between 2006 and 2011. Information on prior eradication therapies was gathered and their impact on the development of antimicrobial resistance, in particular to levofloxacin/ciprofloxacin and triple resistance, was analysed. RESULTS From 2006 onwards, both levofloxacin/ciprofloxacin and triple resistance have steadily increased and peaked in 2011 with 29.1% and 18.6%, respectively. Unsuccessful prior eradication attempts proved a major risk factor for resistance development. Patients who had undergone unsuccessful eradication attempts harboured levofloxacin/ciprofloxacin- and triple-resistant isolates significantly more often than untreated individuals (26.7% and 18.1% versus 10.6% and 1.6%). Levofloxacin/ciprofloxacin and triple resistance occurred significantly more often in patients who had received quinolones when compared with patients who had not (44.5% versus 23.1% and 28.7% versus 15.6%). We did not observe any significant differences in resistance rates in the different German federal states. CONCLUSIONS Resistance to levofloxacin/ciprofloxacin and triple resistance have continuously risen and reached worrying numbers. Hence we strongly advise against the use of quinolones in empirical second-line therapies for H. pylori without prior susceptibility testing and/or a carefully taken patient medical history.
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Affiliation(s)
- Nicole Wueppenhorst
- National Reference Centre for Helicobacter pylori, Department of Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University Medical Centre Freiburg, Hermann-Herder-Str. 11, 79104 Freiburg, Germany
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Abstract
GOALS To determine the susceptibility of Helicobacter pylori strains isolated from a Vietnamese population to 5 antibiotics. BACKGROUND The incidence of antibiotic resistance in H. pylori infection is increasing worldwide and has become a leading cause for failure of treatment. Antibiotic susceptibility testing is very important to provide optimal regimens in a clinical setting. STUDY We isolated 103 H. pylori strains from the gastric mucosa of H. pylori-infected patients from 2 areas in Vietnam (Ho Chi Minh and Hanoi) in 2008. Epsilometer test was used to determine the minimum inhibitory concentrations of amoxicillin, clarithromycin (CLR), metronidazole (MNZ), levofloxacin, and tetracycline. RESULTS Among the 103 strains, the resistance rates were 0% (amoxicillin), 33% (CLR), 69.9% (MNZ), 18.4% (levofloxacin), and 5.8% (tetracycline). The resistant strains showed a high-level of resistance (≥ 256 µg/mL) to CLR, 23.5% (8/34), and MNZ, 29.1% (21/72). The resistance rate for CLR was significantly higher in Ho Chi Minh than in Hanoi (49% vs. 18.5%, P=0.001). Resistance to both CLR and MNZ was most commonly observed (24.3%). Two strains (1.9%) were resistant to 4 of the 5 antibiotics. No significant association was observed between antibiotic resistance rates and age, sex, or clinical outcomes of the patients. CONCLUSIONS High incidence of resistance to CLR and MNZ suggests that standard triple therapies may not be useful as first-line treatment in Vietnam. Alternative strategies such as bismuth-based quadruple therapies or sequential therapy may be more effective in Vietnam.
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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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Cuadrado-Lavín A, Salcines-Caviedes JR, Carrascosa MF, Dierssen-Sotos T, Cobo M, Campos MR, Ayestarán B, Fernández-Pousa A, González-Colominas E, Aresti-Zárate S, Hernández M, Pascual EL. Levofloxacin versus clarithromycin in a 10 day triple therapy regimen for first-line Helicobacter pylori eradication: a single-blind randomized clinical trial. J Antimicrob Chemother 2012; 67:2254-9. [PMID: 22687889 DOI: 10.1093/jac/dks209] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND There is growing evidence that the standard triple therapy against Helicobacter pylori infection is losing clinical effectiveness. A triple therapy regimen with levofloxacin, amoxicillin and a proton pump inhibitor has been reported to be effective and well tolerated, and this regimen has been suggested as an alternative first-line treatment. The aim of this single-blind randomized clinical trial was to compare the eradication success of two first-line triple therapy regimens in the north of Spain: clarithromycin, amoxicillin and omeprazole (CAO) versus levofloxacin, amoxicillin and omeprazole (LAO). MATERIALS AND METHODS A total of 250 consecutive patients diagnosed by conventional methods with H. pylori infection were randomized into one of two 10 day therapeutic regimens: standard CAO (n = 128) or LAO (n = 122). Eradication was confirmed by the (13)C-urea breath test. Adverse effects and compliance were also assessed. The clinical trial registration number was HPL08001HCLAD (EudraCT: 2008-001892-31). RESULTS Intention-to-treat cure rates were: CAO, 75.0% (96/128; 95% CI: 66.6%-82.2%) and LAO, 82.8% (101/122; 95% CI: 74.9%-89.0%). Per-protocol cure rates were: CAO, 78.0% (96/123; 95% CI: 69.7%-85.0%) and LAO, 83.1% (98/118; 95% CI: 75.0%-89.3%). There were no statistically significant differences in effectiveness between the two regimens. In addition, no relevant differences in compliance or adverse effects were demonstrated. CONCLUSIONS Levofloxacin-based treatment for H. pylori infection did not improve upon the eradication rate of the standard clarithromycin-based triple therapy in this study. This may reflect the progressive increase in in vitro resistance rates to levofloxacin observed in our region.
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Affiliation(s)
- Antonio Cuadrado-Lavín
- Department of Gastroenterology, Hospital of Laredo-Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Avda Derechos Humanos s/n, 39770 Laredo, Cantabria, Spain
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Chang WL, Kao CY, Wu CT, Huang AH, Wu JJ, Yang HB, Cheng HC, Sheu BS. Gemifloxacin can partially overcome quinolone resistance of H. pylori with gyrA mutation in Taiwan. Helicobacter 2012; 17:210-5. [PMID: 22515359 DOI: 10.1111/j.1523-5378.2012.00935.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUNDS The levofloxacin resistance caused by gyrA gene mutation is rising rapidly to limit wide application for Helicobacter pylori eradication. We investigated whether gemifloxacin has a superior antimicrobial activity to levofloxacin against H. pylori. MATERIALS AND METHODS Forty-four consecutive clinical H. pylori isolates with levofloxacin resistance and 80 randomly selected levofloxacin-sensitive controls were tested for gemifloxacin sensitivity by E-test. The resistance to levofloxacin or gemifloxacin was defined as minimal inhibitory concentration (MIC) > 1 mg/L. The clinical features and GyrA mutation patterns checked by direct sequencing were also analyzed to assess its association with the H. pylori gemifloxacin resistance. RESULTS All levofloxacin-sensitive H. pylori isolates were sensitive to gemifloxacin. Eight strains (18.2%) resistant to levofloxacin could be still sensitive to gemifloxacin. Gemifloxacin achieved a 5-time lower in MIC levels against levofloxacin-resistant isolates. Nearly all levofloxacin-resistant isolates (97.7%, 43/44) had GyrA mutation at amino acid position 87 or 91. Double mutation sites may play dual roles in quinolone resistance, as N87K plus H57Y or D91N plus V77A mutations showed high-level resistance to both quinolones; whereas D91Y plus A97V or D91N plus A97V mutations showed low level levofloxacin resistance to become sensitive to gemifloxacin. In H. pylori isolates with single N87K, D91Y or D91N mutation, near 20% was gemifloxacin-sensitive and levofloxacin-resistant. The gemifloxacin-resistant rate of H. pylori was higher in patients with gastric ulcer than in those without (p <.05). CONCLUSION Gemifloxacin is superior to levofloxacin in antimicrobial activity against clinical H. pylori isolates, and even overcome some levofloxacin resistance.
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Affiliation(s)
- Wei-Lun Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Gisbert JP. Rescue Therapy for Helicobacter pylori Infection 2012. Gastroenterol Res Pract 2012; 2012:974594. [PMID: 22536225 PMCID: PMC3299261 DOI: 10.1155/2012/974594] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2011] [Accepted: 12/10/2011] [Indexed: 12/18/2022] Open
Abstract
Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After 30 years of experience in H. pylori treatment, however, the ideal regimen to treat this infection has still to be found. Nowadays, apart from having to know well first-line eradication regimens, we must also be prepared to face treatment failures. In designing a treatment strategy, we should not only focus on the results of primary therapy alone but also on the final-overall-eradication rate. The choice of a "rescue" treatment depends on which treatment is used initially. If a first-line clarithromycin-based regimen was used, a second-line metronidazole-based treatment (quadruple therapy) may be used afterwards, and then a levofloxacin-based combination would be a third-line "rescue" option. Alternatively, it has recently been suggested that levofloxacin-based "rescue" therapy constitutes an encouraging 2nd-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, quadruple regimen may be reserved as a 3rd-line "rescue" option. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several "rescue" therapies are consecutively given.
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Affiliation(s)
- Javier P. Gisbert
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
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Variability in Prevalence ofHelicobacter pyloriStrains Resistant to Clarithromycin and Levofloxacin in Southern Poland. Gastroenterol Res Pract 2012; 2012:418010. [PMID: 22693490 PMCID: PMC3368181 DOI: 10.1155/2012/418010] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2012] [Revised: 03/15/2012] [Accepted: 03/29/2012] [Indexed: 02/07/2023] Open
Abstract
Background. An increasing resistance ofHelicobacter pyloristrains to antimicrobial agents is the serious therapeutic problem. The aim of this study was to compare the primary and secondary resistance ofH. pyloristrains isolated between 2006–2008 (data published) and 2009–2011 to clarithromycin and levofloxacin.Material and Methods. 220 dyspeptic patients (153 before treatment, 67 after), were enrolled in the study. 51H. pyloristrains were isolated. MIC values of clarithromycin and levofloxacin were determined by theE-test method. The statistical analysis was conducted with theχ2test with Yates correction at the 0.05 significance level (P≤0.05).Results. Between 2006 and 2008, 34% (39/115) ofH. pyloristrains were resistant to clarithromycin (primary 21% (19/90), secondary 80% (20/25)). 5% (6/115) of strains were resistant to levofloxacin (primary 2% (2/90), secondary 16% ((4/25); data published) Between 2009–2011, 22% (11/51) ofH. pyloristrains were resistant to clarithromycin (primary 19% (8/43), secondary 38% (3/8)). 16% (8/51) of strains were resistant to levofloxacin (primary 12% (5/43), secondary 38% (3/8)).Conclusion. The present study has shown the increasing amount of resistantH. pyloristrains isolated from patients in Southern Poland to levofloxacin and decreasing number of resistant strains to clarithromycin.
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Garcia M, Raymond J, Garnier M, Cremniter J, Burucoa C. Distribution of spontaneous gyrA mutations in 97 fluoroquinolone-resistant Helicobacter pylori isolates collected in France. Antimicrob Agents Chemother 2012; 56:550-1. [PMID: 22064536 PMCID: PMC3256052 DOI: 10.1128/aac.05243-11] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2011] [Accepted: 10/24/2011] [Indexed: 01/30/2023] Open
Abstract
We determined the prevalence of gyrA mutations conferring fluoroquinolone resistance in 97 Helicobacter pylori isolates collected in France from 2007 to 2010. Ninety-four harbored one or two mutations already found in the quinolone resistance determining region (QRDR) of gyrA (for T87I, n = 23; for N87K, n = 32; for D91N, n = 30; for D91G, n = 7; for D91Y, n = 6), 2 harbored a mutation never previously described (D91H and A88P), and one strain was resistant (ciprofloxacin MIC of 8 mg/liter) without a detected mutation conferring this resistance in gyrA or gyrB genes.
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Affiliation(s)
- Magali Garcia
- EA 4331 LITEC, Université de Poitiers, CHU de Poitiers, Laboratoire de Bactériologie-Hygiène, Poitiers, France
| | - Josette Raymond
- CHU Cochin Port Royal, Unité Postulante de Pathogénèse de Helicobacter, Institut Pasteur, Paris, France
| | - Martine Garnier
- EA 4331 LITEC, Université de Poitiers, CHU de Poitiers, Laboratoire de Bactériologie-Hygiène, Poitiers, France
| | - Julie Cremniter
- EA 4331 LITEC, Université de Poitiers, CHU de Poitiers, Laboratoire de Bactériologie-Hygiène, Poitiers, France
| | - Christophe Burucoa
- EA 4331 LITEC, Université de Poitiers, CHU de Poitiers, Laboratoire de Bactériologie-Hygiène, Poitiers, France
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Karczewska E, Wojtas-Bonior I, Sito E, Zwolińska-Wcisło M, Budak A. Primary and secondary clarithromycin, metronidazole, amoxicillin and levofloxacin resistance to Helicobacter pylori in southern Poland. Pharmacol Rep 2011; 63:799-807. [PMID: 21857091 DOI: 10.1016/s1734-1140(11)70592-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2010] [Revised: 12/21/2010] [Indexed: 12/14/2022]
Abstract
The aim of this study was to assess the primary and secondary resistance of H. pylori strains cultured from adult patients of the Małopolska region of Poland, mainly of Kraków and the surrounding areas, to antibacterial agents (amoxicillin, clarithromycin, metronidazole and levofloxacin). In total, 115 H. pylori strains were isolated, of which 90 strains originated from patients who had never been treated for H. pylori infection, while the remaining 25 were isolated from patients in whom eradication of the infection failed after treatment. All tested H. pylori strains were susceptible to amoxicillin. Forty-four percent of strains isolated were resistant to metronidazole. The primary and secondary resistance to this antimicrobial chemotherapeutic reached 37% and 72% (p = 0.002), respectively. In total, 34% of strains were resistant to clarithromycin, and the ratio of strains with secondary resistance was significantly greater than that of the strains with primary resistance (80% vs. 21%, p < 0.001). The double resistance to both metronidazole and clarithromycin was confirmed in 23% of H. pylori strains. Five percent of H. pylori strains were resistant to levofloxacin, while primary and secondary resistance to this drug accounted for 2% and 16% (p = 0.006), respectively. In total, 4% of H. pylori strains were simultaneously resistant to metronidazole, clarithromycin and levofloxacin. Thus, the high resistance to metronidazole and clarithromycin excludes the possibility of using these drugs for treatment of H. pylori infection without earlier antibiogramming. Levofloxacin, as a drug of high efficacy against H. pylori, should be reserved for an "emergency" therapy and used in a limited capacity in order to preserve its potent antimicrobial activity. The Polish Society of Gastroenterology recommends levofloxacin as a third-line therapy.
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Affiliation(s)
- Elżbieta Karczewska
- Department of Pharmaceutical Microbiology of the Jagiellonian University Medical College, Medyczna 9, PL 30-688 Kraków, Poland.
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Cuadrado-Lavín A, Salcines-Caviedes JR, Carrascosa MF, Mellado P, Monteagudo I, Llorca J, Cobo M, Campos MR, Ayestarán B, Fernández-Pousa A, González-Colominas E. Antimicrobial susceptibility of Helicobacter pylori to six antibiotics currently used in Spain. J Antimicrob Chemother 2011; 67:170-3. [PMID: 21965436 DOI: 10.1093/jac/dkr410] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Antibiotic resistance is directly related to the loss of efficacy of currently accepted Helicobacter pylori therapies. Knowledge of the antibiotic susceptibility in a local area can contribute to the design of specific 'à la carte' treatments. The aim of this study was to analyse the susceptibility of H. pylori isolates to six conventional antibiotics currently used in a northern region of Spain. METHODS Seventy-one isolates were obtained from gastric biopsies of 76 consecutive adult patients suffering from peptic ulcer disease, dyspepsia or familial gastric cancer and known to be infected with H. pylori by conventional methods. Susceptibility testing was performed for amoxicillin, ciprofloxacin, levofloxacin, clarithromycin, metronidazole and tetracycline using the Etest method. RESULTS The prevalence rates of resistance were as follows: amoxicillin, 1.4% [95% confidence interval (CI) 0.0-7.6]; clarithromycin, 14.7% (95% CI 7.3-25.4); ciprofloxacin, 14.3% (95% CI 7.1-24.7); levofloxacin, 14.5% (95% CI 7.2-25.0); metronidazole, 45.1% (95% CI 33.2-57.3); and tetracycline, 0% (95% CI 0.0-5.1). CONCLUSIONS Our study confirms an increasing rate of resistance to levofloxacin that equals that of clarithromycin in our healthcare area. This fact may reflect a wide and indiscriminate use of the former antibiotic and could account for a loss of clinical effectiveness of levofloxacin-containing regimens. Moreover, clarithromycin resistance rates remain stable, which could allow us to maintain its use in our area.
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Affiliation(s)
- Antonio Cuadrado-Lavín
- Department of Gastroenterology, Hospital of Laredo-Instituto de Formación e Investigación Marqués de Valdecilla, Avda Derechos Humanos s/n, 39770 Laredo, Cantabria, Spain
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Miendje Deyi VY, Burette A, Bentatou Z, Maaroufi Y, Bontems P, Lepage P, Reynders M. Practical use of GenoType® HelicoDR, a molecular test for Helicobacter pylori detection and susceptibility testing. Diagn Microbiol Infect Dis 2011; 70:557-60. [PMID: 21696906 DOI: 10.1016/j.diagmicrobio.2011.05.002] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2011] [Revised: 04/29/2011] [Accepted: 05/04/2011] [Indexed: 12/12/2022]
Abstract
Compared to culture-based method, the sensitivity, specificity, positive, and negative predictive values of the GenoType(®) HelicoDR for detecting Helicobacter pylori resistance were, respectively, 100, 86.2, 89.7%, and 100% to clarithromycin as well as 82.6, 95.1, 90.5%, and 90.7% to fluoroquinolones. This molecular assay detected a mixture of genotypes and could successfully analyze biopsies without transport/storage limitations.
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Affiliation(s)
- Véronique Yvette Miendje Deyi
- Section of Microbiology, Clinical Biology Department, Brugmann University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
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Francesco VD, Zullo A, Hassan C, Giorgio F, Rosania R, Ierardi E. Mechanisms of Helicobacter pylori antibiotic resistance: An updated appraisal. World J Gastrointest Pathophysiol 2011; 2:35-41. [PMID: 21860834 PMCID: PMC3158889 DOI: 10.4291/wjgp.v2.i3.35] [Citation(s) in RCA: 100] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2011] [Revised: 05/29/2011] [Accepted: 06/05/2011] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) antibiotic resistance is the main factor affecting the efficacy of the current eradicating therapies. The aim of this editorial is to report on the recent information about the mechanisms accounting for the resistance to the different antibiotics currently utilized in H. pylori eradicating treatments. Different mechanisms of resistance to clarithromycin, metronidazole, quinolones, amoxicillin and tetracycline are accurately detailed (point mutations, redox intracellular potential, pump efflux systems, membrane permeability) on the basis of the most recent data available from the literature. The next hope for the future is that by improving the knowledge of resistance mechanisms, the elaboration of rational and efficacious associations for the treatment of the infection will be possible. Another auspicious progress might be the possibility of a cheap, feasible and reliable laboratory test to predict the outcome of a therapeutic scheme.
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Yu C, Li L, Chen W, Jiao Y, Yang N, Yang E, Zhang J, Chen L, Li Y. Levofloxacin susceptibility testing for Helicobacter pylori in China: comparison of E-test and disk diffusion method. Helicobacter 2011; 16:119-23. [PMID: 21435089 DOI: 10.1111/j.1523-5378.2011.00820.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aims of this study were to compare disk diffusion with E-test method for levofloxacin susceptibility testing of Helicobacter pylori and standardized breakpoints for disk diffusion as a stable and reliable method for determining qualitative levofloxacin susceptibility. MATERIALS AND METHODS We determined the levofloxacin susceptibility of 45 H. pylori strains isolated from Chinese patients by the E-test method. Disk diffusion was evaluated as an alternative method to determine susceptibility and compared with the E-test results by linear regression analysis. RESULTS The minimum inhibitory concentration (MIC) values tested by E-test method ranged from 0.047 to 32 μg/mL. Resistance to levofloxacin was detected in 16 (35.6%) isolates. The levofloxacin disk zone sizes obtained by disk diffusion method correlated well (r² = .877) with the MICs obtained by E-test method. As a consequence of regression analysis, isolates with inhibition diameters < 12 mm were considered resistant to levofloxacin. There was 100% agreement between the two methods for levofloxacin, applying the regression-based breakpoints. CONCLUSIONS The disk diffusion method is equivalent to the E-test method for testing levofloxacin susceptibility of H. pylori strains; it is more practical and inexpensive, and it is suitable for the analysis of a small number of isolates compared with the E-test method.
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Affiliation(s)
- Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Multicenter survey of routine determinations of resistance of Helicobacter pylori to antimicrobials over the last 20 years (1990 to 2009) in Belgium. J Clin Microbiol 2011; 49:2200-9. [PMID: 21450969 DOI: 10.1128/jcm.02642-10] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
We analyzed the rates of antimicrobial resistance of Helicobacter pylori strains isolated from patients from 1990 to 2009 and identified risk factors associated with resistance. Gastric biopsy specimens were collected from several digestive disease centers in Brussels, Belgium. We routinely performed antimicrobial susceptibility testing for clarithromycin (CLR), metronidazole, amoxicillin, tetracycline, and ciprofloxacin. Evaluable susceptibility testing was obtained for 9,430 strains isolated from patients who were not previously treated for Helicobacter pylori infection (1,527 isolates from children and 7,903 from adults) and 1,371 strains from patients who were previously treated (162 isolates from children and 1,209 from adults). No resistance to amoxicillin was observed, and tetracycline resistance was very rare (<0.01%). Primary metronidazole resistance remained stable over the years, with significantly lower rates for isolates from children (23.4%) than for isolates from adults (30.6%). Ciprofloxacin resistance remained rare in children, while it increased significantly over the last years in adults. Primary clarithromycin resistance increased significantly, reaching peaks in 2000 for children (16.9%) and in 2003 for adults (23.7%). A subsequent decrease of resistance rates down to 10% in both groups corresponded to a parallel decrease in macrolide consumption during the same period. Multivariate logistic regression revealed that female gender, age of the patient of 40 to 64 years, ethnic background, the number of previously unsuccessful eradication attempts, and the different time periods studied were independent risk factors of resistance to clarithromycin, metronidazole, and ciprofloxacin. Our study highlights the need to update local epidemiological data. Thus, the empirical CLR-based triple therapy proposed by the Maastricht III consensus report remains currently applicable to our population.
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Abstract
New generations of fluoroquinolones, like levofloxacin and moxifloxacin, exhibit a broad-spectrum activity against Gram-positive and Gram-negative bacteria, and have been successfully introduced into the treatment of Helicobacter pylori infection. Based on a large body of evidence, current guidelines recommend the use of levofloxacin- or moxifloxacin-containing proton-pump inhibitor (PPI) triple therapies in second-line or rescue treatment of H. pylori infection. The efficacy of standard PPI triple therapies has substantially declined during the last decade, mainly due to increasing resistance against the key antibiotics clarithromycin and metronidazole. Therefore, alternative strategies for first-line therapy of H. pylori infection have been evaluated in a considerable number of clinical trials including sequential regimens, nonbismuth quadruple regimens, and quinolone-containing PPI triple therapy regimens. The aim of this paper is to summarize the current body of evidence of levofloxacin- and moxifloxacin-containing regimens in first-line treatment of H. pylori infection, and to discuss the risks and benefits of these strategies in the light of increasing resistance of H. pylori to quinolones.
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Affiliation(s)
- Marco Berning
- Medical Department I, University Hospital Carl Gustav Carus, Technical University Dresden, Germany
| | - Susanne Krasz
- Medical Department I, University Hospital Carl Gustav Carus, Technical University Dresden, Germany
| | - Stephan Miehlke
- Medical Department I, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstr. 74, 01307 Dresden Germany
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Genotypic resistance in Helicobacter pylori strains correlates with susceptibility test and treatment outcomes after levofloxacin- and clarithromycin-based therapies. Antimicrob Agents Chemother 2010; 55:1123-9. [PMID: 21189342 DOI: 10.1128/aac.01131-10] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The accuracy of genotypic resistance to levofloxacin (gyrA mutations) and its agreement with treatment outcomes after levofloxacin-based therapy have not been reported. We aimed to assess the correlation. Helicobacter pylori strains isolated from patients who received levofloxacin-based and clarithromycin-based triple therapies in a previous randomized trial were analyzed for point mutations in gyrA and 23S rRNA. PCR followed by direct sequencing was used to assess the gyrA and 23S rRNA mutations. An agar dilution test was used to determine the MICs of clarithromycin and levofloxacin. We found that the agreement between genotypic and phenotypic resistance to levofloxacin was best when the MIC breakpoint was >1 μg/ml (kappa coefficient, 0.754). The eradication rates in patients with and without gyrA mutations were 41.7% and 82.7%, respectively (P = 0.003). The agreement between genotypic and phenotypic resistance to clarithromycin was best when the MIC breakpoint was >2 μg/ml (kappa, 0.694). The eradication rates in patients with and without 23S rRNA mutations were 7.7% and 93.5%, respectively (P < 0.001). The agreements (kappa coefficient) between therapeutic outcomes after clarithromycin-based triple therapy and genotypic and phenotypic resistance were 0.671 and 0.356, respectively. The agreements (kappa coefficient) between therapeutic outcomes after levofloxacin-based triple therapy and genotypic and phenotypic resistance were 0.244 and 0.190, respectively. In conclusion, gyrA and 23S rRNA mutations in H. pylori strains appeared to be better markers than phenotypic resistance in the prediction of treatment outcomes. The optimal breakpoints for levofloxacin and clarithromycin resistance appeared to be >1 μg/ml and >2 μg/ml, respectively.
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Kostamo P, Veijola L, Oksanen A, Sarna S, Rautelin H. Recent trends in primary antimicrobial resistance of Helicobacter pylori in Finland. Int J Antimicrob Agents 2010; 37:22-5. [PMID: 21084175 DOI: 10.1016/j.ijantimicag.2010.09.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2010] [Revised: 08/16/2010] [Accepted: 09/27/2010] [Indexed: 12/18/2022]
Abstract
The antimicrobial susceptibility of Helicobacter pylori is an important predictor of the success of eradication therapy. To evaluate recent changes in primary antimicrobial resistance of H. pylori isolated from Finnish patients, the clinical records of H. pylori-positive patients referred for endoscopy to Herttoniemi Hospital (Helsinki, Finland) during 2000-2008 were investigated retrospectively. Stored H. pylori strains from 505 patients without previous eradication therapy were tested for clarithromycin, metronidazole, levofloxacin, tetracycline and amoxicillin susceptibility by Etest. Data on local consumption of antimicrobials were collected and correlations between consumption and resistance were calculated. During the 9-year study period, metronidazole resistance was high (range 29-59%, overall 41%). After an initial increase in clarithromycin resistance (0% in 2000 to 16% in 2003), resistance to clarithromycin decreased to 4% in 2008. No significant correlation was detected between consumption of macrolides and resistance of clarithromycin. Resistance to levofloxacin varied between 0% and 12%. Primary metronidazole resistance in H. pylori is at a high level, however levofloxacin and clarithromycin resistances are still at a reasonable level. Thus, primary clarithromycin resistance in H. pylori in Finland has not become such a problem as in many other countries. Primary resistance to the antimicrobials studied varied considerably from year to year.
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Affiliation(s)
- Pirkko Kostamo
- Helsinki Health Care, Kettutie 8 M, 00800 Helsinki, Finland.
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Affiliation(s)
- Javier P Gisbert
- Department of Gastroenterology, Hospital Universitario de la Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Playa de Mojácar 29, Madrid, Spain.
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Assem M, El Azab G, Rasheed MA, Abdelfatah M, Shastery M. Efficacy and safety of Levofloxacin, Clarithromycin and Esomeprazol as first line triple therapy for Helicobacter pylori eradication in Middle East. Prospective, randomized, blind, comparative, multicenter study. Eur J Intern Med 2010; 21:310-4. [PMID: 20603042 DOI: 10.1016/j.ejim.2010.05.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2010] [Revised: 05/17/2010] [Accepted: 05/19/2010] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIMS Antibiotic resistance and poor compliance are the main causes of Helicobacter pylori (H. pylori ) eradication failure. This study evaluated the eradication rate, tolerability, and compliance of Levofloxacin, Clarithromycin and Esomeprazol combined triple therapy for H. pylori eradication. PATIENTS AND METHODS Four hundred-fifty patients from 3 centres who were diagnosed to have Helicobacter pylori infection by (13)C-urea breath test were randomized into 3 equal groups; group 1 (CAE) received Clarithromycin 500mg twice daily, Amoxicillin 1000mg twice daily, plus Esomeprazol 20mg twice daily for 7 days, group 2 (LAE) received Levofloxacin 500mg once daily, Amoxicillin 1000mg twice daily, plus Esomeprazol 20mg twice daily for 7 days, group 3 (CLE) received Levofloxacin 500mg once daily, Clarithromycin 500mg twice daily, plus Esomeprazol 20mg twice daily for 7 days. 436 patients were re-evaluated by (13)C-urea breath test after 6weeks from completion of treatment. RESULTS H. pylori eradication (intention to treat) was successful in 136/150 (90.6%) with CLE, 127/150 (84.7%) with LAE and 118/150 (78.6%) with CAE. There was a significant difference (p<0.001) regarding treatment success between CLE and LAE when compared with CAE. There was no difference among the treatment groups with regard to the incidence and severity of adverse events reported. CONCLUSION The combined Levofloxacin, and Clarithromycin and Esomeprazol based regimen as first line triple therapy for H. pylori eradication can give more significant eradication rate with same safety when compared with classic triple therapy.
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Affiliation(s)
- M Assem
- Hepatology Department, National Liver Institute, Sheben Al koom, Egypt.
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Yang JC, Lee PI, Hsueh PR. In vitro activity of nemonoxacin, tigecycline, and other antimicrobial agents against Helicobacter pylori isolates in Taiwan, 1998-2007. Eur J Clin Microbiol Infect Dis 2010; 29:1369-75. [PMID: 20658256 DOI: 10.1007/s10096-010-1009-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2010] [Accepted: 06/20/2010] [Indexed: 12/17/2022]
Abstract
The minimum inhibitory concentrations (MICs) of 330 nonduplicate Helicobacter pylori isolates to nemonoxacin, tigecycline, and eight other antimicrobial agents were determined by using the agar dilution method. Sequencing the quinolone resistance-determining regions (QRDRs) in the gyrA gene of these isolates was also performed. Resistance to clarithromycin showed an increasing trend during the ten-year study period and was highest (38%) in 2005. Tigecycline had potent in vitro activities against all isolates, with an MIC(90) of 0.06 μg/ml. Among the quinolones tested, nemonoxacin (MIC(50) of 0.12 μg/ml and MIC(90) of 0.25 μg/ml) and gemifloxacin had one to two-fold better in vitro activities than ciprofloxacin, levofloxacin, and moxifloxacin. Among the nine isolates (2.7%) with levofloxacin resistance, four (44.4%) were also resistant to metronidazole, three (33.3%) to clarithromycin, and two (22.2%) to amoxicillin. Isolates with levofloxacin resistance exhibited one or two of three amino acid alterations (Ser-70, Asn-87, and Asp-91) involved in QRDRs in the gyrA gene. A double mutation at Ser70Cys and Asn87Ile had a higher level of resistance. The results of this study suggest a potentially useful role of nemonoxacin and tigecycline in the treatment of infections caused by H. pylori. The gyrA mutation at Ser-70 is a novel finding and has an impact on levofloxacin resistance.
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Affiliation(s)
- J-C Yang
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
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Boyanova L, Mitov I. Geographic map and evolution of primary Helicobacter pylori resistance to antibacterial agents. Expert Rev Anti Infect Ther 2010; 8:59-70. [PMID: 20014902 DOI: 10.1586/eri.09.113] [Citation(s) in RCA: 86] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Antibiotic resistance in Helicobacter pylori is the major cause of eradication failure. Primary H. pylori susceptibility patterns, however, are becoming less predictable. Currently, high (> or =20%) clarithromycin resistance rates have been observed in the USA and in developed countries in Europe and Asia, while the highest (> or =80%) metronidazole-resistance rates have been reported in Africa, Asia and South America. Primary quinolone-resistance rates of 10% or more have already been reported in developed countries in Europe and Asia. Primary amoxicillin resistance has been low (0 to <2%) in Europe but higher (6-59%) in Africa, Asia and South America. Similarly, tetracycline resistance has been absent or low (<5%) in most countries and higher (9-27%) in Asia and South America. The increasing clarithromycin and quinolone resistance, and multidrug resistance detected in 0 to less than 5% in Europe and more often (14.2%) in Brazil are worrying. Growing resistance often parallels national antibiotic consumption and may vary within patient groups according to the geographic region, patient's age and sex, type of disease, birthplace, other infections and other factors. The geographic map and evolution of primary H. pylori resistance are clinically important, should be considered when choosing eradication regimens, and should be monitored constantly at national and global levels in an attempt to reach the recently recommended goal of eradication of more than 95%.
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Affiliation(s)
- Lyudmila Boyanova
- Department of Medical Microbiology, Medical University of Sofia, Zdrave street 2, 1431 Sofia, Bulgaria.
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Vécsei A, Kipet A, Innerhofer A, Graf U, Binder C, Gizci H, Hammer K, Bruckdorfer A, Huber WD, Hirschl AM, Makristathis A. Time trends of Helicobacter pylori resistance to antibiotics in children living in Vienna, Austria. Helicobacter 2010; 15:214-20. [PMID: 20557363 DOI: 10.1111/j.1523-5378.2010.00753.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Increase of antibiotic resistance is a worldwide problem. Within the 4 years before the turn of the millennium Helicobacter pylori strains isolated in children living in Vienna, Austria, showed a primary clarithromycin and metronidazole resistance of 20% and 16%, respectively. The aim of this retrospective follow-up survey was to assess the further development and current antimicrobial resistance status. METHODS Children having undergone upper endoscopy between March 2002 and March 2008 at the same two co-operating pediatric gastroenterology units which had also been collaborating on the prior assessment were included. H. pylori infection was diagnosed by rapid urease test, histology, and culture. If the latter was positive, susceptibility testing to amoxicillin, clarithromycin and metronidazole by E-test followed. From March 2004 onwards, susceptibility to levofloxacin, tetracycline and rifampin was additionally assessed. RESULTS Out of 897 children, 153 had a proven infection with H. pylori and no history of prior eradication treatment. Their median age was 11.5 years (range 0.5-20.9 years). Primary resistance to clarithromycin and metronidazole were 34% and 22.9%, respectively; dual resistance was found in 9.8% of the strains; 0.9% was resistant to tetracycline and rifampin, respectively. No case of amoxicillin resistance was detected. The only independent risk factor for clarithromycin resistance turned out to be the origin of a child from Austrian parents. CONCLUSIONS In the last decade, the rate of primary resistance of H. pylori to clarithromycin continued to rise. No significant change was found regarding primary resistance to metronidazole or dual resistance to metronidazole and clarithromycin, respectively.
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Wang LH, Cheng H, Hu FL, Li J. Distribution of gyrA mutations in fluoroquinolone-resistant Helicobacter pylori strains. World J Gastroenterol 2010; 16:2272-7. [PMID: 20458765 PMCID: PMC2868221 DOI: 10.3748/wjg.v16.i18.2272] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the resistance of Helicobacter pylori (H. pylori) to ciprofloxacin (CIP), levofloxacin (LVX) and moxifloxacin (MOX) in the Beijing area and to elucidate the resistance mechanisms.
METHODS: Seventy-nine H. pylori clinical strains, isolated from patients who had undergone upper gastrointestinal endoscopy in Peking University First Hospital from 2007 to 2009, were tested for their susceptibility to CIP, LVX and MOX using the E-test method. H. pylori strain 26695 was included in the susceptibility testing as a control strain. According to the minimal inhibitory concentration (MIC) values, a strain was classified as resistant to CIP, LVX or MOX when the MIC was > 1 μg/mL. We amplified by polymerase chain reaction (PCR) and sequenced the quinolone resistance-determining regions of the gyrA and gyrB genes from 29 quinolone-resistant and 16 quinolone-susceptible H. pylori strains selected at random.
RESULTS: In this study, the resistance rates of H. pylori to CIP, LVX or MOX were 55.7% (44/79), and the primary resistance rates were 26.6% (21/79). Patients with secondary resistance had received LVX in previous eradication treatments, but not MOX or CIP. Forty-five strains, including 29 CIP, LVX or MOX-resistant strains (MIC: 1.5-32 μg/mL) and 16 susceptible strains, were selected randomly from the 79 strains and used in PCR analysis. Among these 45 strains, 27 resistant strains had mutations in the gyrA gene, including 11 strains with mutations corresponding to Asp-91 (MIC: 2-32 μg/mL), one of which also had a mutation corresponding to Val-150, and 16 strains had mutations at Asn-87 (MIC: 4-32 μg/mL), three of which also had mutations corresponding to Arg-140 or Val-150. In addition, Arg-140, Val-150 or Ala-97 mutations were separately detected in three susceptible strains. Analysis of the gyrB gene showed that one strain of low resistance had a mutation corresponding to Ser-457 that coexisted with an Asp-91 mutation. There was a significant difference in the occurrence of mutations in the gyrA gene between CIP, LVX and MOX-resistant and -susceptible strains (P < 0.05), but 2 resistant strains were found to possess no quinolone resistance-determining region mutations.
CONCLUSION: Resistance is primarily mediated through point mutations in gyrA. Whether other mechanisms are responsible for resistance in strains without mutations in the QRDR should be detected.
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Bago J, Majstorović K, Belosić-Halle Z, Kućisec N, Bakula V, Tomić M, Bago P, Troskot R. Antimicrobial resistance of H. pylori to the outcome of 10-days vs. 7-days Moxifloxacin based therapy for the eradication: a randomized controlled trial. Ann Clin Microbiol Antimicrob 2010; 9:13. [PMID: 20398300 PMCID: PMC2867970 DOI: 10.1186/1476-0711-9-13] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2010] [Accepted: 04/15/2010] [Indexed: 12/17/2022] Open
Abstract
Introduction Antibiotic resistance decreases success of Helicobacter pylori (Hp) eradication. Recently published results show low rate of resistance and better compliance with moxifloxacin based regiments. Aims&methods Whether 7 days moxifloxacin with lansoprasole and amoxycillin can be compared with 10 days moxifloxacin with lansoprasole and amoxycillin according to moxifloxacin resistance. Patients with non-ulcer dyspepsia who had culture and histology positive Hp infection (n = 150) were randomly assigned into two groups. The first group (n = 75) received moxifloxacin 400 mg/d during 7 days and the other (n = 75) received moxifloxacin 400 mg/d during 10 days. All patients received amoxycillin 1 g twice daily, lansoprasole 30 mg twice daily. All Hp cultures were tested for sensitivity to moxifloxacin. Results 138 patients (92%) completed the study, 68 in the first group and 70 in the second. Eradication rates were 84% (57/68) and 76% (57/75) in the 7 days moxifloxacin group and 90% and 84% in the second group (63/70, 63/75) according to the PP and ITT analysis; p = n.s. Among 129 patients (86% of study group), 6% of strains were primary resistant to moxifloxacin. Eradication of moxifloxacin sensitive/resistant strains was 98%/66%, p < 0.05 Conclusion According to our results we recommend 7 days moxiflixacin based triple therapy.
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Affiliation(s)
- Josip Bago
- Department of Gastroenterology, Internal Medicine Clinic, Clinical Hospital Sveti Duh, Zagreb, Croatia.
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Ramírez FB, Torres ER, Carmona JA. Criterios actuales para la erradicación de Helicobacter pylori. FMC - FORMACIÓN MÉDICA CONTINUADA EN ATENCIÓN PRIMARIA 2010; 17:158-166. [DOI: 10.1016/s1134-2072(10)70063-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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