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Wang Y, Du J, Zhang D, Jin C, Chen J, Wang Z, Mei T, Fu K, Qian Q, Pang T. Primary antibiotic resistance in Helicobacter pylori in China: a systematic review and meta-analysis. J Glob Antimicrob Resist 2023; 34:30-38. [PMID: 37315738 DOI: 10.1016/j.jgar.2023.05.014] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 05/25/2023] [Accepted: 05/31/2023] [Indexed: 06/16/2023] Open
Abstract
OBJECTIVES The incidence of Helicobacter pylori (HP) is 25-50% in developed countries and 80% in developing countries, including 56.2% in China. However, antibiotic resistance of HP is a threat to HP control. The purpose of this study was to comprehensively evaluate primary drug resistance of HP in China. METHODS The full text of reports of the primary antibiotic resistance prevalence of HP was obtained from multiple databases (PubMed, Web of Science, Evimed, Cochrane Library, and China National Knowledge Internet). Review Manager 5.2 was adopted for meta-analysis, sensitivity analysis, and bias analysis. The Newcastle-Ottawa Scale was used to assess the article quality. RESULTS In total, 38804 HP samples from 22 trials were extracted. The results suggested that the overall prevalence of amoxicillin, clarithromycin, metronidazole, and levofloxacin resistance among HP in adults was as follows: mean difference (MD) = 1.35%, 95% confidence interval (CI) [1.03%, 1.68%]; MD = 23.76%, 95% CI [20.23%, 27.3%]; MD = 69.32%, 95% CI [64.85%, 73.8%]; and MD = 29.45%, 95% CI [4.90, 176.96], respectively. From the results of sensitivity and publication bias, we find that these results are robust and had little publication bias. CONCLUSION Our research showed that in China, the prevalence of HP resistance to primary antibiotics warrants attention, especially with regard to metronidazole, levofloxacin, and clarithromycin.
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Affiliation(s)
- Yuxiang Wang
- School of Public Health, North China University of Science and Technology, Taiyuan, China
| | - Jinran Du
- Biotecnovo (Langfang) Medical Lab Co. Ltd., Langfang, China
| | - Dayan Zhang
- Wanquan District Hospital of Traditional Chinese Medicine, Zhangjiakou City, Hebei Province, China
| | - Cong Jin
- School of Public Health, North China University of Science and Technology, Taiyuan, China
| | - Jiangpo Chen
- Biotecnovo (Langfang) Medical Lab Co. Ltd., Langfang, China
| | - Zeyuan Wang
- Beijing Sentum Health Co., Ltd., Beijing, China
| | - Tonglin Mei
- Beijing Sentum Health Co., Ltd., Beijing, China
| | - Kaili Fu
- Beijing Sentum Health Co., Ltd., Beijing, China
| | - Qingzeng Qian
- School of Public Health, North China University of Science and Technology, Taiyuan, China.
| | - Tieliang Pang
- Biotecnovo (Langfang) Medical Lab Co. Ltd., Langfang, China.
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Yuan C, Yu C, Sun Q, Xiong M, Zhou S, Zeng M, Song H. Research on antibiotic resistance in Helicobacter pylori: a bibliometric analysis of the past decade. Front Microbiol 2023; 14:1208157. [PMID: 37389333 PMCID: PMC10301835 DOI: 10.3389/fmicb.2023.1208157] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 05/25/2023] [Indexed: 07/01/2023] Open
Abstract
Resistance of Helicobacter pylori (H. pylori) to antibiotics has reached alarming levels worldwide, and the efficacy of the H. pylori eradication treatment has decreased dramatically because of antibiotic resistance. To gain a more comprehensive understanding of the development status, research hotspots, and future trends related to H. pylori antibiotic resistance, we conducted a thorough retrospective analysis via the bibliometrics method. We searched the Science Citation Index Expanded of the Web of Science Core Collection for all pertinent articles on H. pylori antibiotic resistance from 2013 to 2022. R-bibliometrix, CiteSpace, and VOSviewer tools were utilized to depict statistical evaluations in order to provide an unbiased presentation and forecasts in the field. We incorporated a total of 3,509 articles related to H. pylori antibiotic resistance. Publications were inconsistent prior to 2017, but steadily increased after 2017. China generated the most papers and the United States of America received the most citations and the highest H-index. Baylor College of Medicine was the most influential institution in this field, with the highest number of publications and citations, as well as the highest H-index. Helicobacter was the most productive journal, followed by the World Journal of Gastroenterology and Frontiers in Microbiology. The World Journal of Gastroenterology had the highest citation. Graham, David Y was the most productive and cited author. Clarithromycin resistance, prevalence, gastric cancer, quadruple therapy, sequential therapy, 23S rRNA, whole genome sequencing, bismuth, and probiotics appeared with a high frequency in the keywords. The top keywords with the highest citation bursts were vonoprazan, RdxA, biofilm formation, and fatty acid chain. Our research illustrated a multi-dimensional facet and a holistic knowledge structure for H. pylori antibiotic resistance research over the past decade, which can serve as a guide for the H. pylori research community to conduct in-depth investigations in the future.
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Affiliation(s)
- Chengzhi Yuan
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, China
- School of Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Chang Yu
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, China
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Qifang Sun
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, China
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Meng Xiong
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, China
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Sainan Zhou
- The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Meiyan Zeng
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Houpan Song
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, China
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
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Moghadam MT, Chegini Z, Norouzi A, Dousari AS, Shariati A. Three-Decade Failure to the Eradication of Refractory Helicobacter pylori Infection and Recent Efforts to Eradicate the Infection. Curr Pharm Biotechnol 2021; 22:945-959. [PMID: 32767919 DOI: 10.2174/1389201021666200807110849] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 06/30/2020] [Accepted: 07/04/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Helicobacter pylori causes dangerous and deadly diseases such as gastric cancer and duodenal ulcers. Eradication and treatment of this bacterium are very important due to the deadly diseases caused by H. pylori and the high cost of treatment for countries. METHODS Thus, we present a complete list of the most important causes of failure in the treatment and eradication of H. pylori, and address new therapeutic methods that may be effective in controlling this bacterium in the future. RESULTS Many efforts have been made to control and eradicate this bacterium over the years, but no success has been achieved since its eradication is a complex process affected by the bacterial properties and host factors. Previous studies have shown that various factors are involved in the failure to eradicate H. pylori, such as new genotypes of the bacterium with higher pathogenicity, inappropriate patient cooperation, mutations, biofilm formation and dormant forms that cause antibiotic resistance, acidic stomach pH, high bacterial load, smoking, immunosuppressive features and intracellular occurrence of H. pylori. On the other hand, recent studies reported that the use of probiotics, nanoparticles, antimicrobial peptides, natural product and vaccines can be helpful in the treatment and eradication of H. pylori infections. CONCLUSION Eradication of H. pylori is crucial for the treatment of important diseases such as gastric cancer. Therefore, it seems that identifying the failure causes of treating this bacterium can be helpful in controlling the infections. Besides, further studies on new therapeutic strategies may help eradicate H. pylori in the future.
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Affiliation(s)
- Majid T Moghadam
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zahra Chegini
- Student Research Committee, Iran University of Medical Sciences, Tehran, Iran
| | - Amin Norouzi
- Department of Microbiology and Virology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Aref Shariati
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Camorlinga-Ponce M, Gómez-Delgado A, Aguilar-Zamora E, Torres RC, Giono-Cerezo S, Escobar-Ogaz A, Torres J. Phenotypic and Genotypic Antibiotic Resistance Patterns in Helicobacter pylori Strains From Ethnically Diverse Population in México. Front Cell Infect Microbiol 2021; 10:539115. [PMID: 33643927 PMCID: PMC7905308 DOI: 10.3389/fcimb.2020.539115] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 12/30/2020] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori strains carry a range of mutations in genes that confer antimicrobial resistance and restrict the available options to treat the infection. Latin America is a region that conserve a large number of indigenous communities relatively isolated that practice a traditional medicine without consumption of drugs. We hypothesized that rates of antibiotic resistance are lower in these communities. Recent progress in whole-genome sequencing has allowed the study of drug susceptibility by searching for the known mutations associated with antibiotic resistance. The aim of this work was to study trends of antibiotic resistance over a 20-year period in Mexican H. pylori strains and to compare susceptibility between strains from Mexican mestizos and from indigenous population; we also aimed to learn the prevalence of mutational patterns in genes gyrA, gyrB, rdxA, frxA, rpsU, omp11, dppA, and 23S rRNA and its association with phenotypic tests. Resistance to clarithromycin, metronidazole, amoxicillin and levofloxacin was determined in167 H. pylori isolates by E-test, and the occurrence of mutational patterns in specific genes was determined by whole genome sequencing (WGS). The trend of resistance over 20 years in mestizo isolates showed significant resistant increase for clarithromycin and levofloxacin to frequencies that banned its clinical use. Resistance in H. pylori isolates of native communities was lower for all antibiotics tested. Phenotypic resistance showed good to moderate correlation with genotypic tests. Genetic methods for characterizing antibiotic resistance require further validation in each population.
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Affiliation(s)
- Margarita Camorlinga-Ponce
- Unidad de Investigación en Enfermedades Infecciosas, UMAE Pediatría, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico
| | - Alejandro Gómez-Delgado
- Unidad de Investigación en Enfermedades Infecciosas, UMAE Pediatría, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico
| | - Emmanuel Aguilar-Zamora
- Unidad de Investigación en Enfermedades Infecciosas, UMAE Pediatría, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico.,Posgrado en Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, Mexico
| | - Roberto C Torres
- Unidad de Investigación en Enfermedades Infecciosas, UMAE Pediatría, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico
| | - Silvia Giono-Cerezo
- Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, Mexico
| | - Antonio Escobar-Ogaz
- Unidad de Investigación en Enfermedades Infecciosas, UMAE Pediatría, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico
| | - Javier Torres
- Unidad de Investigación en Enfermedades Infecciosas, UMAE Pediatría, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico
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Mascellino MT, Oliva A, Miele MC, De Angelis M, Bruno G, Severi C. Secondary Antibiotic Resistance, Correlation between Genotypic and Phenotypic Methods and Treatment in Helicobacter pylori Infected Patients: A Retrospective Study. Antibiotics (Basel) 2020; 9:E549. [PMID: 32872117 PMCID: PMC7560230 DOI: 10.3390/antibiotics9090549] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 08/17/2020] [Accepted: 08/25/2020] [Indexed: 02/07/2023] Open
Abstract
The aim of this study was to evaluate the secondary resistance in Helicobacter pylori (Hp) infected patients who had failed a first-line therapy, and to compare the genotypic tests performed directly on gastric samples with phenotypic tests performed on culture media. The eradication rate of patients treated with bismuth quadruple therapy (BQT) is also evaluated. A total of 80 positive specimens were retrospectively examined. Antibiotic susceptibility testing of Hp strains was performed by E-test, whereas a molecular commercially available method was used for detecting the mutations involved in clarithromycin and levofloxacin resistance. High resistance levels to metronidazole and clarithromycin (61.6% and 35%, respectively) and worrying resistance levels to levofloxacin (15%) were found phenotypically. Multiple resistance to two or three antibiotics was observed as well. The polymorphism A2143G on clarithromycin 23S rRNA gene was found in 34/80 (42.5%) isolates including 10 mixed infections (29%), whereas 28/80 (35%) strains were resistant phenotypically. Levofloxacin resistance corresponded to 30% by PCR and 15% by E-test (statistically significant, p < 0.05). The knowledge of clarithromycin and levofloxacin resistance is crucial to establish an appropriate therapy in different geographical areas. The genetic methods were superior to phenotypic techniques in the absence of live bacteria or for identifying mixed infections that may lead to a resistance underestimation. The BQT eradication rate was effective (90%).
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Affiliation(s)
- Maria Teresa Mascellino
- Department of Public Health and Infectious Diseases, Sapienza University, 00185 Rome, Italy; (A.O.); (M.C.M.); (M.D.A.)
| | - Alessandra Oliva
- Department of Public Health and Infectious Diseases, Sapienza University, 00185 Rome, Italy; (A.O.); (M.C.M.); (M.D.A.)
| | - Maria Claudia Miele
- Department of Public Health and Infectious Diseases, Sapienza University, 00185 Rome, Italy; (A.O.); (M.C.M.); (M.D.A.)
| | - Massimiliano De Angelis
- Department of Public Health and Infectious Diseases, Sapienza University, 00185 Rome, Italy; (A.O.); (M.C.M.); (M.D.A.)
| | - Giovanni Bruno
- Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy; (G.B.); (C.S.)
| | - Carola Severi
- Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy; (G.B.); (C.S.)
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High Prevalence of Antibiotic Resistance in Iranian Helicobacter pylori Isolates: Importance of Functional and Mutational Analysis of Resistance Genes and Virulence Genotyping. J Clin Med 2019; 8:jcm8112004. [PMID: 31744181 PMCID: PMC6912791 DOI: 10.3390/jcm8112004] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 11/11/2019] [Accepted: 11/14/2019] [Indexed: 12/14/2022] Open
Abstract
The high prevalence of antibiotic resistance in Helicobacter pylori has become a great challenge in Iran. The genetic mutations that contribute to the resistance have yet to be precisely identified. This study aimed to investigate the prevalence of antibiotic resistance and virulence markers in Iranian H. pylori isolates and to analyze if there is any association between resistance and genotype. Antibiotic susceptibility patterns of 68 H. pylori isolates were investigated against metronidazole, clarithromycin, amoxicillin, rifampicin, ciprofloxacin, levofloxacin, and tetracycline by the agar dilution method. The frxA, rdxA, gyrA, gyrB, and 23S rRNA genes of the isolates were sequenced. The virulence genotypes were also determined using PCR. Metronidazole resistance was present in 82.4% of the isolates, followed by clarithromycin (33.8%), ciprofloxacin (33.8%), rifampicin (32.4%), amoxicillin (30.9%), levofloxacin (27.9%), and tetracycline (4.4%). Overall, 75% of the isolates were resistant to at least two antibiotics tested and considered as a multidrug resistance (MDR) phenotype. Most of the metronidazole-resistant isolates carried frameshift mutations in both frxA and rdxA genes, and premature termination occurred in positions Q5Stop and Q50Stop, respectively. Amino acid substitutions M191I, G208E, and V199A were predominantly found in gyrA gene of fluoroquinolone-resistant isolates. A2143G and C2195T mutations of 23S rRNA were found in four clarithromycin-resistant isolates. Interestingly, significant associations were found between resistance to metronidazole (MNZ) and cagA-, sabA-, and dupA-positive genotypes, with p = 0.0002, p = 0.0001, and p = 0.0001, respectively. Furthermore, a significant association was found between oipA “on” status and resistance to amoxicillin (AMX) (p = 0.02). The prevalence of H. pylori antibiotic resistance is high in our region, particularly that of metronidazole, clarithromycin, ciprofloxacin, and MDR. Simultaneous screening of virulence and resistance genotypes can help clinicians to choose the appropriate therapeutic regime against H. pylori infection.
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Kouitcheu Mabeku LB, Eyoum Bille B, Tepap Zemnou C, Tali Nguefack LD, Leundji H. Broad spectrum resistance in Helicobacter pylori isolated from gastric biopsies of patients with dyspepsia in Cameroon and efflux-mediated multiresistance detection in MDR isolates. BMC Infect Dis 2019; 19:880. [PMID: 31640588 PMCID: PMC6806547 DOI: 10.1186/s12879-019-4536-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 10/09/2019] [Indexed: 12/17/2022] Open
Abstract
Background Antibiotic resistance is a leading cause of treatment failure in Helicobacter pylori infection. In Africa, there are very little data concerning the susceptibility of Helicobacter pylori isolates to antibiotics. The purpose of this study was to evaluate the resistance prevalence of Helicobacter pylori strains circulating in Cameroon, and to assess overexpression of efflux pump as a possible multi-drug resistance mechanisms. Methods A total of 140 H. pylori isolates were recovered from gastric biopsies of dyspeptic patients in two reference hospitals in Cameroon and analyzed for their antimicrobial susceptibility to amoxicillin, co-amoxiclav, ampicillin, penicillin, imipenem, metronidazole, rifabutin, erythromycin, clarithromycin, azithromycin, levofloxacin, ciprofloxacin, norfloxacin, tetracycline, doxycycline and minocycline. Antibiotic sensitivity was tested by disk diffusion method. Phe-Arg-naphthylamide (PAßN) was used as efflux pump inhibitor. INT broth microdilution method in supplemented Brain Heart Infusion broth was used to determine the MIC of ampicillin, amoxicillin, metronidazole, erythromycin, clarithromycin and doxycycline in the absence and the presence of PAßN against 32 selected MDR isolates. Results Overall H. pylori resistance rate was 100% to ampicillin, penicillin and co-amoxiclav; 97.14% to amoxicillin, 97.85% to metronidazole, 47.85% to erythromycin, 13.57% to clarithromycin; 5, 2.86 and 0.71% to doxycycline, tetracycline and minocycline respectively. No resistance to azithromycin, rifabutin, imipenem, ciprofloxacin, norfloxacin and levofloxacin was detected among H. pylori isolates. Seventy percent (70%) of the tested isolates elicited a multiple drugs resistance pattern; 42.57% double, 15.71% triple and 5.71% quadruple drugs resistance. Metronidazole and amoxicillin were more concerned with double resistance pattern (86.76%). The spectrum of activity recorded with metronidazole, doxycycline, clarithromycin and erythromycin ranged from 0 to 100% in the absence to the presence of PAßN against the tested MDR isolates. An 8 to 128-fold increase in potency was also noticed with these antibiotics in the presence of PAßN. Conclusion With regard to the high resistance rate to both amoxicillin and metronidazole, these drugs should be avoided as components of triple therapy in our milieu. In contrast, ciprofloxacin, norfloxacin, levofloxacin and tetracyclines could be used to achieve a better eradication rate and to reduce the risk of selection of H. pylori resistant strains.
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Affiliation(s)
- Laure Brigitte Kouitcheu Mabeku
- Microbiology and Pharmacology Laboratory, Department of Biochemistry, Faculty of Science, University of Dschang, P. O. Box, 67, Dschang, Cameroon.
| | - Bertrand Eyoum Bille
- Microbiology and Pharmacology Laboratory, Department of Biochemistry, Faculty of Science, University of Dschang, P. O. Box, 67, Dschang, Cameroon
| | - Cromwell Tepap Zemnou
- Microbiology and Pharmacology Laboratory, Department of Biochemistry, Faculty of Science, University of Dschang, P. O. Box, 67, Dschang, Cameroon
| | - Lionel Danny Tali Nguefack
- Microbiology and Pharmacology Laboratory, Department of Biochemistry, Faculty of Science, University of Dschang, P. O. Box, 67, Dschang, Cameroon
| | - Hubert Leundji
- Gastroenterology Department, Laquintinie Hospital of Douala, P. O. Box, 4035, Douala, Cameroon
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Inference from the analysis of genetic structure of Helicobacter pylori strains isolates from two paediatric patients with recurrent infection. BMC Microbiol 2019; 19:184. [PMID: 31395006 PMCID: PMC6686460 DOI: 10.1186/s12866-019-1554-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2019] [Accepted: 07/26/2019] [Indexed: 01/06/2023] Open
Abstract
Background Helicobacter pylori recurrence after successful eradication is an important problem. Children are particularly vulnerable to reinfection, by intrafamilial transmission which facilitates the acquisition or recombination of new genetic information by this bacterium. We investigated the evolutionary dynamics of 80 H. pylori strains isolated from two paediatric patients with recurrent infection (recrudescence and reinfection). Results We characterized the virulence genes vacA (s1, m1, s2, and m2), cagA, cagE, and babA2 and performed multilocus sequence typing (MLST) on 7 housekeeping genes (atpA, efp, ureI, ppa, mutY, trpC, and yphC) to infer the evolutionary dynamics of the H. pylori strains through phylogenetic and genealogic inference analyses, genetic diversity analysis and the exploration of recombination events during recurrent infections. The virulence genotype vacAs1m1/cagA+/cagE+/babA2 was present at a high frequency, as were the EPIYA motifs EPIYA-A, −B and -C. Furthermore, the housekeeping genes of the H. pylori strains exhibited high genetic variation, comprising 26 new alleles and 17 new Sequence Type (ST). In addition, the hpEurope (76.5%) and hspWAfrica (23.5%) populations predominated among the paediatric strains. All strains, regardless of their ancestral affiliation, harboured western EPIYA motifs. Conclusions This study provides evidence of the evolutionary dynamics of the H. pylori strains in two paediatric patients during recrudescence and reinfection events. In particular, our study shows that the strains changed during these events, as evidenced by the presence of different STs that emerged before and after treatment; these changes may be due to the accumulation of mutations and recombination events during the diversification process and recolonization of the patients by different genotypes. Electronic supplementary material The online version of this article (10.1186/s12866-019-1554-z) contains supplementary material, which is available to authorized users.
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Escobedo-Belloc M, Bosques-Padilla F. The rise of antibiotic resistance to Helicobacter pylori in Mexico: Is azithromycin plus levofloxacin the answer? REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2019. [DOI: 10.1016/j.rgmxen.2018.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
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Helicobacter pylori eradication in Mexico with a levofloxacin-based scheme versus standard triple therapy: Results from an open-label, randomized, noninferiority phase IIIb trial. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2019. [DOI: 10.1016/j.rgmxen.2018.09.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
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Escobedo-Belloc M, Bosques-Padilla F. The rise of Helicobacter pylori resistance to antibiotics in Mexico: Is azithromycin plus levofloxacin the answer? REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2019; 84:271-273. [PMID: 31047738 DOI: 10.1016/j.rgmx.2018.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Accepted: 10/10/2018] [Indexed: 06/09/2023]
Affiliation(s)
- M Escobedo-Belloc
- Hospital Universitario, Departamento de Gastroenterología, Universidad Autónoma de Nuevo León (UANL), Monterrey, México
| | - F Bosques-Padilla
- Facultad de Medicina, Universidad Autónoma de Nuevo León (UANL), Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Dirección Médica Hospital San José, Monterrey, México.
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Ladrón-de-Guevara L, Bornstein-Quevedo L, González-Huezo S, Castañeda-Romero B, Costa FG, di Silvio-López M. Helicobacter pylori eradication in Mexico with a levofloxacin-based scheme versus standard triple therapy: Results from an open-label, randomized, noninferiority phase iiib trial. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2018; 84:274-283. [PMID: 30060902 DOI: 10.1016/j.rgmx.2018.04.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Revised: 03/26/2018] [Accepted: 04/19/2018] [Indexed: 01/15/2023]
Abstract
INTRODUCTION AND AIMS Helicobacter pylori (H. pylori) infection remains the leading cause of several gastroduodenal diseases. Despite the fact that multiple antibiotic regimens have been used to change its associated morbidity and mortality, the prevalence of this bacterial infection continues to be disproportionately high worldwide, mainly due to antibiotic resistance. To assess the noninferiority efficacy and safety of 210-day triple regimens on H. pylori eradication, we evaluated clarithromycin 500mg, lansoprazole 30mg, and amoxicillin 1g, all bid (standard triple therapy or CLA, Group 1) vs. pantoprazole 80mg, levofloxacin 500mg and azithromycin 500mg, all od (PLA, Group 2). Both regimens were compared in treatment-naïve patients. MATERIALS AND METHODS An open label phase IIIb randomized and noninferiority trial comparing CLA vs. PLA was carried out for a 10-day period, within the time frame of June 2012 and March 2014. Eradication was verified with 13C-urea breath testing. Gastric biopsies were tested for fluorescence in situ hybridization (FISH)-clarithromycin resistance prior to any antibiotic administration. Efficacy and safety results were analyzed according to the noninferiority methodological approach. RESULTS From the 227 H. pylori positive subjects that were randomized, 194 were finally analyzed as per-protocol. The group 2 eradication rate was 63% and was noninferior to the group 1 eradication rate of 58.5% (upper limit 95% CI: 0.11608; below the noninferiority margin: 0.1200). FISH clarithromycin-resistance was found in 28.2% of the cases. Adverse events, all minor and self-limited, were significantly higher in group 1 than in group 2 (86 vs. 65.4%; p=0.001). CONCLUSIONS First-line H. pylori eradication with pantoprazole/levofloxacin/azithromycin combination therapy is as effective as the standard triple therapy, with better tolerability and easier dosing. Clarithromycin resistance should be considered when selecting antibiotics in Helicobacter pylori eradication treatments. ClinicalTrials.gov identifier NCT02726269.
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Affiliation(s)
- L Ladrón-de-Guevara
- Servicio de Gastroenterología, Hospital Ángeles Clínica Londres, Ciudad de México, México
| | - L Bornstein-Quevedo
- Laboratorio de Inmunohistoquímica y Patología Molecular, InmunoQ, Ciudad de México, México
| | - S González-Huezo
- Servicio de Gastroenterología, Torre Mayo, Metepec, Estado de México, México
| | - B Castañeda-Romero
- Servicio de Gastroenterología, Hospital Ángeles Metropolitano, Ciudad de México, México
| | - F G Costa
- Laboratorio Asofarma S.A.I. y C. Argentina.
| | - M di Silvio-López
- Servicio de Gastroenterología, Centro Médico ABC Observatorio, Ciudad de México, México
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Bosques-Padilla F, Remes-Troche J, González-Huezo M, Pérez-Pérez G, Torres-López J, Abdo-Francis J, Bielsa-Fernandez M, Constanza-Camargo M, Esquivel-Ayanegui F, Garza-González E, Hernández-Guerrero A, Herrera-Goepfert R, Huerta-Iga F, Leal-Herrera Y, Lopéz-Colombo A, Ortiz-Olvera N, Riquelme-Pérez A, Sampieri C, Uscanga-Domínguez L, Velarde-Ruiz Velasco J. The fourth Mexican consensus on Helicobacter pylori. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2018. [DOI: 10.1016/j.rgmxen.2018.07.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
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The fourth Mexican consensus on Helicobacter pylori. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2018; 83:325-341. [PMID: 29941237 DOI: 10.1016/j.rgmx.2018.05.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 05/12/2018] [Accepted: 05/25/2017] [Indexed: 12/14/2022]
Abstract
Important advances have been made since the last Mexican consensus on the diagnosis and treatment of Helicobacter pylori (H. pylori) infection was published in 2007. Therefore, the Asociación Mexicana de Gastroenterología summoned 20 experts to produce "The Fourth Mexican Consensus on Helicobacter pylori". From February to June 2017, 4 working groups were organized, a literature review was performed, and 3 voting rounds were carried out, resulting in the formulation of 32 statements for discussion and consensus. From the ensuing recommendations, it was striking that Mexico is a country with an intermediate-to-low risk for gastric cancer, despite having a high prevalence of H. pylori infection. It was also corroborated that peptic ulcer disease, premalignant lesions, and histories of gastric cancer and mucosa-associated lymphoid tissue lymphoma should be considered clear indications for eradication. The relation of H. pylori to dyspeptic symptoms continues to be controversial. Eradication triple therapy with amoxicillin, clarithromycin, and a proton pump inhibitor should no longer be considered first-line treatment, with the following 2 options proposed to take its place: quadruple therapy with bismuth (proton pump inhibitor, bismuth subcitrate, tetracycline, and metronidazole) and quadruple therapy without bismuth (proton pump inhibitor, amoxicillin, clarithromycin, and metronidazole). The need for antimicrobial sensitivity testing when 2 eradication treatments have failed was also established. Finally, the promotion of educational campaigns on the diagnosis and treatment of H. pylori for both primary care physicians and the general population were proposed.
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Liu RP, Romero R, Sarosiek J, Dodoo C, Dwivedi AK, Zuckerman MJ. Eradication Rate of Helicobacter pylori on the US-Mexico Border Using the Urea Breath Test. South Med J 2018; 111:51-55. [PMID: 29298370 DOI: 10.14423/smj.0000000000000747] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVES Helicobacter pylori is prevalent worldwide, especially in Latin America. Triple and quadruple antibiotic therapies have been relatively effective; however, resistance has emerged in recent years. The treatment success rate of these regimens on the border of the United States and Mexico is unknown. Our study attempted to determine eradication rates of two major regimens based on urea breath test (UBT) results in patients previously diagnosed as having H. pylori in a single center in El Paso, Texas, a city on the geographic border with Mexico. METHODS This was a retrospective cohort study of adult patients with H. pylori who underwent UBT after being treated with triple therapy (amoxicillin/clarithromycin/proton pump inhibitor for 14 days), quadruple therapy (tetracycline/metronidazole/bismuth/proton pump inhibitor, usually for 10 days), or both for H. pylori from 2010 to 2015 in a county hospital. Patients were excluded if they did not complete therapy or if their treatment regimen was unknown. The Student t test and the χ2 test were used to analyze the data. The cumulative incidence and 95% confidence interval (CI) for treatment success were estimated. RESULTS A total of 104 patients completed the treatment for H. pylori and had UBT. Mean age was 53 years, 76% were women, 85% were Hispanic, and mean body mass index was 30.5 kg/m2. Of the 104 patients diagnosed as having H. pylori, 88 received triple therapy (84.6%) and 16 received quadruple therapy: 12 (11.5%) standard quadruple therapy, 4 (3.9%) triple therapy plus metronidazole. There were no differences between groups regarding age, sex, body mass index, or ethnicity. Overall, 90 (86.5%, 95% CI 78-92) patients had negative UBT after initial treatment. Based on posttreatment UBT, the triple therapy group had a similar eradication rate compared with the quadruple therapy group (78/88, 88.6% vs 12/16, 75.0%, P = 0.22). Of the 14 patients with positive posttreatment UBT, 12 (85.7%) received retreatment (2 were lost to follow-up), 11 (91.7%) received quadruple therapy, and 1 (8.3%) received triple therapy. Eradication was successful in 9 of 12 (75%, 95% CI 43-95) patients at retreatment. As such, of the initial 104 patients, 99/104 (95.2%) achieved H. pylori eradication posttreatment (either initial or retreatment). CONCLUSIONS In a predominantly Hispanic population on the US-Mexico border, H. pylori eradication rates based on UBT results were relatively high and were similar for triple therapy and quadruple therapy. Quadruple therapy was effective for those who failed the initial H. pylori treatment. This may have implications for cost-effective therapy in our region.
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Affiliation(s)
- Roy P Liu
- From the Division of Gastroenterology and the Division of Biostatistics and Epidemiology, Texas Tech University Health Sciences Center, El Paso
| | - Roberta Romero
- From the Division of Gastroenterology and the Division of Biostatistics and Epidemiology, Texas Tech University Health Sciences Center, El Paso
| | - Jerzy Sarosiek
- From the Division of Gastroenterology and the Division of Biostatistics and Epidemiology, Texas Tech University Health Sciences Center, El Paso
| | - Christopher Dodoo
- From the Division of Gastroenterology and the Division of Biostatistics and Epidemiology, Texas Tech University Health Sciences Center, El Paso
| | - Alok K Dwivedi
- From the Division of Gastroenterology and the Division of Biostatistics and Epidemiology, Texas Tech University Health Sciences Center, El Paso
| | - Marc J Zuckerman
- From the Division of Gastroenterology and the Division of Biostatistics and Epidemiology, Texas Tech University Health Sciences Center, El Paso
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Suzuki H, Mori H. World trends for H. pylori eradication therapy and gastric cancer prevention strategy by H. pylori test-and-treat. J Gastroenterol 2018; 53:354-361. [PMID: 29138921 PMCID: PMC5847180 DOI: 10.1007/s00535-017-1407-1] [Citation(s) in RCA: 99] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Accepted: 10/25/2017] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori-associated gastritis leads to the development of gastric cancer. Kyoto global consensus report on H. pylori gastritis recommended H. pylori eradication therapy to prevent gastric cancer. To manage H. pylori infection, it is important to choose the appropriate regimen considering regional differences in resistance to clarithromycin and metronidazole. Quinolones and rifabutin-containing regimens are useful as third- and fourth-line rescue therapies.
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Affiliation(s)
- Hidekazu Suzuki
- Fellowship Training Center, Medical Education Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
| | - Hideki Mori
- Department of Gastroenterology, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan
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17
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Mascellino MT, Porowska B, De Angelis M, Oliva A. Antibiotic susceptibility, heteroresistance, and updated treatment strategies in Helicobacter pylori infection. Drug Des Devel Ther 2017; 11:2209-2220. [PMID: 28814829 PMCID: PMC5546184 DOI: 10.2147/dddt.s136240] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
In this review, we discuss the problem of antibiotic resistance, heteroresistance, the utility of cultures and antibiotic susceptibility tests in Helicobacter pylori (Hp) eradication, as well as the updated treatment strategies for this infection. The prevalence of antibiotic resistance is increasing all over the world, especially for metronidazole and clarithromycin, because of their heavy use in some geographical areas. Heteroresistance (simultaneous presence of both susceptible and resistant strains in different sites of a single stomach) is another important issue, as an isolate could be mistakenly considered susceptible if a single biopsy is used for antimicrobial tests. We also examined literature data regarding eradication success rates of culture-guided and empiric therapies. The empiric therapy and the one based on susceptibility testing, in Hp eradication, may depend on several factors such as concomitant diseases, the number of previous antibiotic treatments, differences in bacterial virulence in individuals with positive or negative cultures, together with local antibiotic resistance patterns in real-world settings. Updated treatment strategies in Hp infection presented in the guidelines of the Toronto Consensus Group (2016) are reported. These suggest to prolong eradication therapy up to 14 days, replacing the old triple therapy with a quadruple therapy based on proton pump inhibitor (PPI), bismuth, metronidazole, and tetracycline for most of the patients, or as an alternative quadruple therapy without bismuth, based on the use of PPI, amoxicillin, metronidazole, and clarithromycin. The new drug vonoprazan, a first-in-class potassium-competitive acid blocker recently approved in Japan, is also considered to be a promising solution for Hp eradication, even for clarithromycin-resistant strains. Furthermore, there is growing interest in finding new therapeutic strategies, such as the development of vaccines or the use of natural resources, including probiotics, plants, or nutraceuticals.
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Affiliation(s)
| | - Barbara Porowska
- Department of Cardio-Thoracic, Vascular, General Surgery and of Organ Transplants, Policlinico Umberto I, Rome, Italy
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Goudarzi M, Heidary M, Azad M, Fazeli M, Goudarzi H. Evaluation of antimicrobial susceptibility and integron carriage in Helicobacter pylori isolates from patients. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2016; 9:S47-S52. [PMID: 28224028 PMCID: PMC5310800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
AIM The purpose of this study was to determine the antibiotic susceptibility pattern and distribution of integron in H. pylori isolates collected from patients referred to private health care centers in Tehran, Iran. BACKGROUND Antibiotic resistance is the main reason for failure of Helicobacter pylori therapy. Integrons as genetic reservoirs play main roles in the dissemination of antimicrobial resistance gene. METHODS During a 12-month cross-sectional study period, 65 H. pylori isolates were recovered from 124 biopsy specimens. Isolates were subjected to susceptibility testing using by Epsilometer test according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline. PCR was used to detect different types of integrons. RESULTS Antimicrobial susceptibility testing revealed that 73.8% of isolates were resistant to metronidazole, 43.1% to clarithromycin, 29.2% to tetracycline, 27.7% to amoxicillin, 23.1% to rifampicin and 13.4% to levofloxacin. Frequency of multidrug resistance among H. pylori isolates was 26.1%. The most predominant resistance profiles among our isolates were included resistance to clarithromycin and metronidazole (20%). Class 1 and 2 integrons were detected in 8 (12.3%) and 15 (23.1%) of the isolates, respectively. CONCLUSIONS The high prevalence of multidrug resistance and frequency of class 2 integron in this survey can be a warning for clinicians. Continuous surveillance is necessary for the development of new treatment protocols to prevent the treatment failures and also further spread of resistant isolates.
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Affiliation(s)
- Mehdi Goudarzi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohsen Heidary
- Department of Medical Microbiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mehdi Azad
- Department of Medical Laboratory Sciences, School of Paramedicine, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Maryam Fazeli
- WHO Collaborating Center for Reference and Research on Rabies, Pasteur Institute of Iran, Tehran, Iran
| | - Hossein Goudarzi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Alarcón-Millán J, Fernández-Tilapa G, Cortés-Malagón EM, Castañón-Sánchez CA, De Sampedro-Reyes J, Cruz-Del Carmen I, Betancourt-Linares R, Román-Román A. Clarithromycin resistance and prevalence of Helicobacter pylori virulent genotypes in patients from Southern México with chronic gastritis. INFECTION GENETICS AND EVOLUTION 2016; 44:190-198. [PMID: 27355861 DOI: 10.1016/j.meegid.2016.06.044] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Revised: 06/21/2016] [Accepted: 06/23/2016] [Indexed: 02/07/2023]
Abstract
In developing countries, clarithromycin resistance and frequency of re-infection are factors that contribute to high prevalence of Helicobacter pylori infection. The aim of this research was determine the prevalence of clarithromycin resistance and its relation with A2142G, A2142C and A2143G mutations in the domain V of the 23S rRNA gene of H. pylori isolates in patients from Southern Mexico with chronic gastritis. Another purpose of this work was to study the prevalence of virulent genotypes and distribution of resistant strains according to the vacA/cagA/babA2 H. pylori genotypes. One hundred forty-four patients with chronic gastritis were studied. Forty-five H. pylori strains were isolated and clarithromycin susceptibility was determined by the disk-diffusion method. The 82.2% of the strains had the combination of alleles vacA s1 m1 and the cagA gene was detected in 77.8% and 40% of the strains were babA2 positive. The vacA s1 m1 genotype was detected more frequently in cagA(+) strains, vacA s1m1/cagA(+)/babA2(-) genotype was more frequent than vacA s1m1/cagA(+)/babA2(+), 37.8% and 33.3%, respectively. Eight strains were clarithromycin resistant, in three of these, point mutations were identified, but only in one strain the A2143G mutation associated with clarithromycin resistance was found. Other point mutations (A1821G, G1826A, T1830C, A2089G, T1600C, C1601T, C1602T, T1610C, A1611C and T1633G) that have not been associated with clarithromycin resistance were identified. The highest proportion of resistant strains was vacA s1m1/cagA(+) (62.5%). In patients from southern Mexico with chronic gastritis, the prevalence of clarithromycin resistance is within internationally accepted range (17.8%) and allows continued use of triple therapy for H. pylori eradication. However, it is necessary to monitor the evolution of clarithromycin resistance in this area. The largest proportion of resistant H. pylori strains is not harboring the A2142G, A2142C and A2143G mutations in the 23S rRNA gene (87.5%). The vacA s1m1/cagA(+) genotype was the most prevalent and among clarithromycin-resistant strains, this was the predominant.
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Affiliation(s)
- Judit Alarcón-Millán
- Laboratorio de Investigación en Bacteriología, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México.
| | - Gloria Fernández-Tilapa
- Laboratorio de Investigación Clínica, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México.
| | - Enoc Mariano Cortés-Malagón
- Laboratorio de Biología Molecular del Cáncer, Unidad de Investigación, Hospital Juárez de México, Ciudad de México, México.
| | | | | | - Iván Cruz-Del Carmen
- Hospital General "Dr. Raymundo Abarca Alarcón", Chilpancingo, Guerrero, México; Unidad Especializada de Gastroenterología Endoscopia, Chilpancingo, Guerrero, México.
| | | | - Adolfo Román-Román
- Laboratorio de Investigación en Bacteriología, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México.
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20
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Goudarzi H, Seyedjavadi SS, Fazeli M, Azad M, Goudarzi M. Genotyping of Peroxisome Proliferator-Activated Receptor gamma in Iranian Patients with Helicobacter pylori Infection. Asian Pac J Cancer Prev 2016. [PMID: 26225656 DOI: 10.7314/apjcp.2015.16.13.5219] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Helicobacter pylori (H. pylori) infection as a serious problem in both adults and children can induce chronic gastritis, peptic ulcer disease (PUD), and possibly gastric cancer. The aim of the current study was to survey antibiotic resistance and also to determine influence of PPARγ polymorphism in patients with H. pylori infection. During an 11-month-period, 98 H. pylori isolates were collected from 104 biopsy specimens. In vitro susceptibility of H. pylori isolates to 4 antimicrobial agents metronidazole, clarithromycin, amoxicillin and tetracycline were assessed by quantitative method according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline. PPARγ polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of H. pylori infection in our study was 94.2%. In vitro susceptibility data showed that highest level of resistance was related to metronidazole (66.3%), and the majority of H. pylori isolates were highly susceptible to amoxicillin and tetracycline (94.9% and 96.9%, respectively). Genotypic frequencies were 25.5% for CC (Pro12Pro), 40.8% for GC (Pro12Ala) and 33.7% for GG (Ala12Ala). In our study, CG genotype had highest distributions among infected patients with H. pylori. The study suggests that the PPAR-γ Pro12Ala polymorphism could be evaluated as a potential genetic marker for susceptibility to gastric cancer in the presence of H. pylori infection.
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Affiliation(s)
- Hossein Goudarzi
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran E-mail :
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Thung I, Aramin H, Vavinskaya V, Gupta S, Park JY, Crowe SE, Valasek MA. Review article: the global emergence of Helicobacter pylori antibiotic resistance. Aliment Pharmacol Ther 2016; 43:514-33. [PMID: 26694080 PMCID: PMC5064663 DOI: 10.1111/apt.13497] [Citation(s) in RCA: 530] [Impact Index Per Article: 58.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Revised: 05/04/2015] [Accepted: 11/19/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Helicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma. AIM To review recent trends in H. pylori antibiotic resistance rates, and to discuss diagnostics and treatment paradigms. METHODS A PubMed literature search using the following keywords: Helicobacter pylori, antibiotic resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing. RESULTS The prevalence of bacterial antibiotic resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other antibiotics show similar trends, although less pronounced. CONCLUSIONS Since the choice of empiric therapies should be predicated on accurate information regarding antibiotic resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric antibiotic therapy but also inform the development of better methods to identify H. pylori antibiotic resistance at diagnosis. Patient-specific tailoring of effective antibiotic treatment strategies may lead to reduced treatment failures and less antibiotic resistance.
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Affiliation(s)
- I. Thung
- Division of Anatomic PathologyDepartment of PathologyUniversity of California San Diego Medical CenterSan DiegoCAUSA
| | - H. Aramin
- Division of Anatomic PathologyDepartment of PathologyUniversity of California San Diego Medical CenterSan DiegoCAUSA
| | - V. Vavinskaya
- Division of Anatomic PathologyDepartment of PathologyUniversity of California San Diego Medical CenterSan DiegoCAUSA
| | - S. Gupta
- Division of GastroenterologyDepartment of MedicineUniversity of California San Diego Medical CenterLa JollaCAUSA
| | - J. Y. Park
- Department of Pathology and the Eugene McDermott Center for Human Growth and DevelopmentUniversity of Texas Southwestern Medical Center and Children's Medical CenterDallasTXUSA
| | - S. E. Crowe
- Division of GastroenterologyDepartment of MedicineUniversity of California San Diego Medical CenterLa JollaCAUSA
| | - M. A. Valasek
- Division of Anatomic PathologyDepartment of PathologyUniversity of California San Diego Medical CenterSan DiegoCAUSA
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Maleknejad S, Mojtahedi A, Safaei-Asl A, Taghavi Z, Kazemnejad E. Primary Antibiotic Resistance to Helicobacter pylori Strains Isolated From Children in Northern Iran: A Single Center Study. IRANIAN JOURNAL OF PEDIATRICS 2015; 25:e2661. [PMID: 26635938 PMCID: PMC4662838 DOI: 10.5812/ijp.2661] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Revised: 08/25/2015] [Accepted: 09/05/2015] [Indexed: 02/06/2023]
Abstract
Background: Initial resistance to antibiotics is the main reason for the failure of Helicobacter pylori (H. pylori) eradication in children. Objectives: As we commonly face high antibiotic resistance rates in children, we aimed to determine the susceptibility of H. pylori to common antibiotics. Patients and Methods: In this cross-sectional in vitro study, 169 children younger than 14 years with clinical diagnosis of peptic ulcer underwent upper gastrointestinal endoscopy. Biopsy specimens from stomach and duodenum were cultured. In isolated colonies, tests of catalase, urease, and oxidase as well as gram staining were performed. After confirming the colonies as H. pylori, the antibiogram was obtained using disk diffusion method. Results: Culture for H. pylori was positive in 12.3% of the specimens, urease test in 21.3%, serological test in 18.9% and stool antigen test was positive in 21.9%. We could show high specificity but moderate sensitivity of both histological and H. pylori stool antigen tests to detect H. pylori. The overall susceptibility to metronidazole was 42.9%, amoxicillin 95.2%, clarithromycin 85.7%, furazolidone 61.9%, azithromycin 81.0%, and tetracycline 76.2% with the highest resistance to metronidazole and the lowest to clarithromycin. Conclusions: In our region, there is high resistance of H. pylori to some antibiotics including metronidazole and furazolidone among affected children. To reduce the prevalence of this antibiotic resistance, more controlled use of antibiotics should be considered in children.
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Affiliation(s)
- Shohreh Maleknejad
- Department of Pediatrics, 17th Shahrivar Hospital, Guilan University of Medical Sciences, Rasht, IR Iran
- Corresponding author: Shohreh Maleknejad, Department of Pediatrics, 17th Shahrivar Hospital, Guilan University of Medical Sciences, Rasht, IR Iran. Tel: +98-1313226101, Fax: +98-1313226101, E-mail:
| | - Ali Mojtahedi
- Department of Pediatrics, 17th Shahrivar Hospital, Guilan University of Medical Sciences, Rasht, IR Iran
| | - Afshin Safaei-Asl
- Department of Pediatrics, 17th Shahrivar Hospital, Guilan University of Medical Sciences, Rasht, IR Iran
| | - Zeinab Taghavi
- Department of Pediatrics, 17th Shahrivar Hospital, Guilan University of Medical Sciences, Rasht, IR Iran
| | - Ehsan Kazemnejad
- Department of Pediatrics, 17th Shahrivar Hospital, Guilan University of Medical Sciences, Rasht, IR Iran
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Three unsuccessful treatments of Helicobacter pylori infection by a highly virulent strain with quadruple antibiotic resistance. Folia Microbiol (Praha) 2015; 61:307-10. [PMID: 26634607 DOI: 10.1007/s12223-015-0439-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2015] [Accepted: 11/25/2015] [Indexed: 01/06/2023]
Abstract
We report a case of an adult patient undergoing three unsuccessful Helicobacter pylori treatments, including proton pump inhibitor (PPI), bismuth subcitrate, metronidazole and tetracycline in 2012, PPI, amoxicillin and clarithromycin in 2013, and PPI, amoxicillin and rifampin in 2014. Following the first treatment, the isolate was metronidazole and ciprofloxacin/levofloxacin resistant. After the second treatment, the isolate was resistant to metronidazole, ciprofloxacin/levofloxacin and rifampin, developing secondary clarithromycin resistance by A2143G mutation and was susceptible only to tetracycline. After the third treatment, the patient still remained H. pylori positive. Patient's strain was highly virulent (cagA (+) , cagE (+) and vacA s1a/m1/i1). The evolution of the patient's disease was from gastroesophageal reflux disease in 2012 to two duodenal ulcers in 2015. Briefly, the infecting strain showed quadruple antibiotic resistance and a transient amoxicillin resistance. Triple clarithromycin-based treatment induced secondary clarithromycin resistance by A2143G mutation, while rifampin resistance caused the third treatment failure. Several options for the next treatment regimens are discussed.
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Gehlot V, Mahant S, Mukhopadhyay AK, Das K, De R, Kar P, Das R. Antimicrobial susceptibility profiles of Helicobacter pylori isolated from patients in North India. J Glob Antimicrob Resist 2015; 5:51-6. [PMID: 27436467 DOI: 10.1016/j.jgar.2015.09.009] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 09/17/2015] [Accepted: 09/30/2015] [Indexed: 12/27/2022] Open
Abstract
Helicobacter pylori-related gastroduodenal diseases are very common in India. Antibiotic resistance to commonly used antibiotics against H. pylori is increasing very rapidly. The aim of this study was to determine the antimicrobial susceptibility patterns of H. pylori strains from India against commonly used antibiotics in H. pylori treatment. Helicobacter pylori were cultured from 68 patients suffering from various gastroduodenal diseases in North India. Minimum inhibitory concentrations (MICs) to different antibiotics were determined by agar dilution. The clinical diagnosis of the 68 patients who were H. pylori culture-positive were gastro-oesophageal reflux disease (GERD) (n=23), non-erosive reflux disease (NERD) (n=22), non-ulcer dyspepsia (NUD) (n=13), antral gastritis (n=3), duodenal ulcer (n=2) and others (n=5). Of the 68 H. pylori isolates, 20 (29.4%) showed no resistance. The prevalence of drug resistance was 70.6%, including resistance to metronidazole (48.5%), furazolidone (22.1%), amoxicillin (17.6%), tetracycline (16.2%) and clarithromycin (11.8%). Dual and multiple drug resistance were found in 26.5% and 8.8% of cases, respectively. In conclusion, more than two-thirds of the isolated H. pylori strains showed resistance to at least one of the antibiotics for H. pylori treatment. Metronidazole resistance was most prevalent amongst the isolates tested. Emergence of dual and multidrug resistance is of great concern and there is an urgent need for regular antibiotic resistance surveillance studies. Amoxicillin- and clarithromycin-based anti-H. pylori regimens commonly prescribed for triple therapy in India show least resistance and hence are appropriate for anti-H. pylori management in India.
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Affiliation(s)
- Valentina Gehlot
- Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
| | - Shweta Mahant
- Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
| | | | - Kunal Das
- Yashoda Superspeciality Hospital, Ghaziabad, Uttar Pradesh, India; Yatharth Wellness Superspeciality Hospital, Noida, Uttar Pradesh, India
| | - Ronita De
- National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India
| | - Premashis Kar
- Maulana Azad Medical College and L.N. Hospital, New Delhi, India
| | - Rajashree Das
- Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India.
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Kim SY, Choi DJ, Chung JW. Antibiotic treatment for Helicobacter pylori: Is the end coming? World J Gastrointest Pharmacol Ther 2015; 6:183-198. [PMID: 26558152 PMCID: PMC4635158 DOI: 10.4292/wjgpt.v6.i4.183] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 08/01/2015] [Accepted: 09/28/2015] [Indexed: 02/06/2023] Open
Abstract
Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori) has been associated with gastro-duodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacillus. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication.
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Ozbey G, Dogan Y, Demiroren K, Ozercan IH. Prevalence of Helicobacter pylori in children in eastern Turkey and molecular typing of isolates. Braz J Microbiol 2015; 46:505-11. [PMID: 26273266 PMCID: PMC4507543 DOI: 10.1590/s1517-838246220140234] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2013] [Accepted: 09/30/2014] [Indexed: 12/19/2022] Open
Abstract
The objectives of the present study were to determine Helicobacter
pylori via culture, polymerase chain reaction and histopathological
diagnosis in 101 children ranging in age from 4 to 18 years, to identify the
association among restriction fragment length polymorphism types and clinical
disease and to investigate the relationships among different isolates of
H. pylori in different age groups. We observed a high
prevalence of H. pylori infections in children between the ages
of 13 and 18 (75.8%), while children aged 4 to 6 years had the lowest prevalence
of infection (40%). H. pylori was detected in 30.7% (31 of
101), 66.3% (67 of 101) and 63.2% (60 of 95) of children as determined by
culture methods, PCR and histological examination, respectively. H.
pylori isolates with RFLP types I and III were the most common
among children with antral nodularity, whereas RFLP types II and IV were the
least detected types. Interestingly, all isolates from peptic ulcer patients
were type III. Although our results show a high prevalence of H.
pylori infections in the pediatric population in eastern Turkey, no
association was identified between H. pylori infection with
antral nodularity and recurring abdominal pain. In addition, we found low
genetic variation among H. pylori isolates from children and no
association between RFLP types and antral nodularity (p > 0.05).
Additionally, we found that H. pylori isolates with specific
RFLP types were predominant in different age groups.
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Affiliation(s)
- Gokben Ozbey
- Firat University, Vocational School of Health Services, Firat University, Elazig, Turkey, Vocational School of Health Services, Firat University, Elazig, Turkey
| | - Yasar Dogan
- Firat University, Department of Pediatric Gastroenterology, Faculty of Medicine, Firat University, Elazig, Turkey, Department of Pediatric Gastroenterology, Faculty of Medicine, Firat University, Elazig, Turkey
| | - Kaan Demiroren
- Firat University, Department of Pediatric Gastroenterology, Faculty of Medicine, Firat University, Elazig, Turkey, Department of Pediatric Gastroenterology, Faculty of Medicine, Firat University, Elazig, Turkey
| | - Ibrahim Hanifi Ozercan
- Firat University, Department of Pathology, Faculty of Medicine, Firat University, Elazig, Turkey, Department of Pathology, Faculty of Medicine, Firat University, Elazig, Turkey
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Heo J, Jeon SW, Jung JT, Kwon JG, Kim EY, Lee DW, Seo HE, Ha CY, Kim HJ, Kim ES, Park KS, Cho KB, Lee SH, Jang BI. A randomised clinical trial of 10-day concomitant therapy and standard triple therapy for Helicobacter pylori eradication. Dig Liver Dis 2014; 46:980-4. [PMID: 25132282 DOI: 10.1016/j.dld.2014.07.018] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Revised: 07/07/2014] [Accepted: 07/20/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND As a result of increased resistance to antibiotics, Helicobacter pylori eradication rates using standard triple therapy have been declining. AIM To validate the efficacy and tolerability of a concomitant regimen as a first-line treatment for H. pylori infection. METHODS A total of 348 naïve H. pylori-infected patients from six hospitals in Korea were randomly assigned to concomitant therapy and standard triple therapy groups. The concomitant regimen consisted of 30 mg of lansoprazole, 1g of amoxicillin, 500 mg of clarithromycin, and 500 mg of metronidazole, twice daily for 10 days. The standard triple regimen consisted of 30 mg of lansoprazole, 1g of amoxicillin, and 500 mg of clarithromycin, twice daily for 10 days. RESULTS Concomitant and standard eradication rates were 78.7% (137/174) vs. 70.7% (123/174) by intention-to-treat (p=0.084) and 88.7% (133/150) vs. 78.4% (120/153) by per-protocol (p=0.016), respectively. The two groups were similar with regard to the incidence of adverse events. CONCLUSIONS Although 10-day concomitant therapy was validated as a suboptimal treatment option for the treatment of H. pylori infection, this regimen is expected to be a promising starting point in the development of an optimal treatment regimen for H. pylori infection.
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Affiliation(s)
- Jun Heo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, South Korea
| | - Seong Woo Jeon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, South Korea.
| | - Jin Tae Jung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, South Korea
| | - Joong Goo Kwon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, South Korea
| | - Eun Young Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, South Korea
| | - Dong Wook Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Daegu Fatima Hospital, Daegu, South Korea
| | - Hyang Eun Seo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Daegu Fatima Hospital, Daegu, South Korea
| | - Chang Yoon Ha
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, South Korea
| | - Hyun Jin Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, South Korea
| | - Eun Soo Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea
| | - Kyung Sik Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea
| | - Kwang Bum Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea
| | - Si Hyung Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, South Korea
| | - Byung Ik Jang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, South Korea
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Shokrzadeh L, Alebouyeh M, Mirzaei T, Farzi N, Zali MR. Prevalence of multiple drug-resistant Helicobacter pylori strains among patients with different gastric disorders in Iran. Microb Drug Resist 2014; 21:105-10. [PMID: 25303151 DOI: 10.1089/mdr.2014.0081] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Emergence of multidrug-resistant (MDR) strains of Helicobacter pylori is a global health concern. This study was aimed to determine the frequency of MDR H. pylori strains in Iran. H. pylori isolates were obtained from cultured gastric biopsy samples on selective culture media after their characterization by PCR and conventional biochemical methods. The minimal inhibitory concentrations of rifampicin, ciprofloxacin, levofloxacin, ampicillin, clarithromycin, erythromycin, metronidazole, and tetracycline were determined for 111 strains that were isolated from 197 dyspeptic patients by the agar dilution method. The primary resistance rates were 61.3% (68/111) for metronidazole, 15.3% (17/111) for ampicillin, and 14.4% (16/111) for rifampicin. Resistance rates for other antimicrobials were as follows: macrolides (erythromycin or clarithromycin) 32.4% (36/111) and quinolones (levofloxacin or ciprofloxacin) 30.6% (34/111). Among the resistant strains, the rates of double and multiple drug resistance phenotypes were 22.6% (19/84) and 34.5% (29/84), respectively. The quadruple drug resistance phenotype encompasses 37.9% of the MDR strains, of which 90% of them was resistant to metronidazole. In conclusion, these results showed a high frequency of MDR phenotypes among the studied H. pylori strains in Iran. The eradication of the H. pylori strains presenting high resistance rates to macrolides, fluoroquinolones, or metronidazole could be achieved by approved tetracycline- or amoxicillin-containing regimens as alternative regimens to standard triple therapy.
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Affiliation(s)
- Leila Shokrzadeh
- 1 Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences , Tehran, Iran
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Bustamante-Rengifo JA, Matta AJ, Pazos A, Bravo LE. In vitro effect of amoxicillin and clarithromycin on the 3’ region of cagA gene in Helicobacter pylori isolates. World J Gastroenterol 2013; 19:6044-6054. [PMID: 24106405 PMCID: PMC3785626 DOI: 10.3748/wjg.v19.i36.6044] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2013] [Revised: 04/04/2013] [Accepted: 05/08/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the in vitro effect of amoxicillin and clarithromycin on the cag pathogenicity island (cag PAI).
METHODS: One hundred and forty-nine clinical isolates of Helicobacter pylori (H. pylori) cultured from gastric biopsies from 206 Colombian patients with dyspeptic symptoms from a high-risk area for gastric cancer were included as study material. Antimicrobial susceptibility was determined by the agar dilution method. Resistant isolates at baseline and in amoxicillin and clarithromycin serial dilutions were subjected to genotyping (cagA, vacA alleles s and m), Glu-Pro-Ile-Tyr-Ala (EPIYA) polymerase chain reaction and random amplified polymorphic DNA (RAPD). Images of the RAPD amplicons were analyzed by Gel-Pro Analyzer 4.5 program. Cluster analyses was done using SPSS 15.0 statistical package, where each of the fingerprint bands were denoted as variables. Dendrograms were designed by following Ward’s clustering method and the estimation of distances between each pair of H. pylori isolates was calculated with the squared Euclidean distance.
RESULTS: Resistance rates were 4% for amoxicillin and 2.7% for clarithromycin with 2% double resistances. Genotyping evidenced a high prevalence of the genotype cagA-positive/vacA s1m1. The 3’ region of cagA gene was successfully amplified in 92.3% (12/13) of the baseline resistant isolates and in 60% (36/60) of the resistant isolates growing in antibiotic dilutions. Upon observing the distribution of the number of EPIYA repetitions in each dilution with respect to baseline isolates, it was found that in 61.5% (8/13) of the baseline isolates, a change in the number of EPIYA repetitions lowered antibiotic pressure. The gain and loss of EPIYA motifs resulted in a diversity of H. pylori subclones after bacterial adjustment to changing conditions product of antibiotic pressure. RAPD PCR evidenced the close clonal relationship between baseline isolates and isolates growing in antibiotic dilutions.
CONCLUSION: Antibiotic pressure does not induce loss of the cag pathogenicity island, but it can lead - in most cases - to genetic rearrangements within the 3’ region cagA of the founding bacteria that can affect the level of tyrosine phosphorylation impacting on its cellular effects and lead to divergence of cagA-positive subclones.
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Morales-Espinosa R, Gonzalez-Valencia G, Delgado G, Navarro A, Garcia V, Cravioto A. Susceptibility Profile to Common Antimicrobials Used for Eradication ofHelicobacter pyloriInfection in Mexico by Agar Dilution Method. J Chemother 2013; 19:108-9. [PMID: 17309863 DOI: 10.1179/joc.2007.19.1.108] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Xiong LJ, Tong Y, Wang Z, Mao M. Detection of clarithromycin-resistant Helicobacter pylori by stool PCR in children: a comprehensive review of literature. Helicobacter 2013; 18:89-101. [PMID: 23067446 DOI: 10.1111/hel.12016] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Helicobacter pylori infection is acquired mainly during childhood. To eradicate H. pylori, clarithromycin-based triple therapy has been recommended in children and adults by the latest Maastricht Consensus. However, the prevalence of clarithromycin-resistant H. pylori was higher in children than that in adults. Therefore, rapid, reliable and noninvasive methods for detecting clarithromycin-resistant H. pylori strains should be developed for children. MATERIALS AND METHODS Studies on evaluating stool PCR in detecting clarithromycin-resistant H. pylori and epidemiological surveys of the prevalence of clarithromycin-resistant H. pylori in children were searched in PubMed (from 1966 to December, 2011) for reviewing. RESULTS The average rates of primary clarithromycin-resistant H. pylori ranged from less than 10% to more than 40% in different regions. The rates of secondary resistance to clarithromycin were higher than primary resistance in the same population. In H. pylori isolated from children, the frequent point mutations that are responsible for the clarithromycin resistance included A2143G, A2142G, A2142C and A2144G, and they varied geographically. Comparing with culture-based susceptibility tests, stool PCR performed excellently for their rapidity, independence of bacterial growth, reproducibility and easy standardization. However, stool PCR showed lower sensitivity but perfect specificity in detection of clarithromycin-resistant H. pylori in children. Methodology and mixed infections of resistant H. pylori strains might contribute to the considerable discrepancies of stool PCR results. CONCLUSION Detection of clarithromycin-resistant H. pylori by stool PCR for children are reliable, rapid, noninvasive methods that are worthy of further clinical promotion. However, more evaluations of stool PCR in detection of clarithromycin-resistant H. pylori in children need to be conducted.
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Affiliation(s)
- Li Jing Xiong
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
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Liou JM, Chen CC, Chen MJ, Chen CC, Chang CY, Fang YJ, Lee JY, Hsu SJ, Luo JC, Chang WH, Hsu YC, Tseng CH, Tseng PH, Wang HP, Yang UC, Shun CT, Lin JT, Lee YC, Wu MS. Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet 2013; 381:205-13. [PMID: 23158886 DOI: 10.1016/s0140-6736(12)61579-7] [Citation(s) in RCA: 197] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Whether sequential treatment can replace triple therapy as the standard treatment for Helicobacter pylori infection is unknown. We compared the efficacy of sequential treatment for 10 days and 14 days with triple therapy for 14 days in first-line treatment. METHODS For this multicentre, open-label, randomised trial, we recruited patients (≥20 years of age) with H pylori infection from six centres in Taiwan. Using a computer-generated randomisation sequence, we randomly allocated patients (1:1:1; block sizes of six) to either sequential treatment (lansoprazole 30 mg and amoxicillin 1 g for the first 7 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg for another 7 days; with all drugs given twice daily) for either 10 days (S-10) or 14 days (S-14), of 14 days of triple therapy (T-14; lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg for 14 days; with all drugs given twice daily). Investigators were masked to treatment allocation. Our primary outcome was the eradication rate in first-line treatment by intention-to-treat (ITT) and per-protocol (PP) analyses. This trial is registered with ClinicalTrials.gov, number NCT01042184. FINDINGS Between Dec 28, 2009, and Sept 24, 2011, we enrolled 900 patients: 300 to each group. The eradication rate was 90·7% (95% CI 87·4-94·0; 272 of 300 patients) in the S-14 group, 87·0% (83·2-90·8; 261 of 300 patients) in the S-10 group, and 82·3% (78·0-86·6; 247 of 300 patients) in the T-14 group. Treatment efficacy was better in the S-14 group than it was in the T-14 group in both the ITT analysis (number needed to treat of 12·0 [95% CI 7·2-34·5]; p=0·003) and PP analyses (13·7 [8·3-40], p=0·003). We recorded no significant difference in the occurrence of adverse effects or in compliance between the three groups. INTERPRETATION Our findings lend support to the use of sequential treatment as the standard first-line treatment for H pylori infection. FUNDING National Taiwan University Hospital and National Science Council.
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Affiliation(s)
- Jyh-Ming Liou
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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The IncF plasmid pRSB225 isolated from a municipal wastewater treatment plant's on-site preflooder combining antibiotic resistance and putative virulence functions is highly related to virulence plasmids identified in pathogenic E. coli isolates. Plasmid 2012; 69:127-37. [PMID: 23212116 DOI: 10.1016/j.plasmid.2012.11.001] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2012] [Revised: 11/12/2012] [Accepted: 11/18/2012] [Indexed: 11/22/2022]
Abstract
The IncF antibiotic resistance and virulence plasmid pRSB225, isolated from an unknown bacterium released with the purified wastewater from a municipal sewage treatment plant into the environment has been analysed at the genomic level by pyrosequencing. The 164,550bp plasmid comprises 210 coding sequences (cds). It is composed of three replicons (RepFIA, RepFIB, and RepFII) and encodes further plasmid-specific functions for stable maintenance and inheritance and conjugative plasmid transfer. The plasmid is self-transmissible and shows a narrow host range limited to the family Enterobacteriaceae. The accessory modules of the plasmid mainly comprise genes conferring resistance to ampicillin (bla(TEM-1b)), chloramphenicol (catA1), erythromycin (mphA), kanamycin and neomycin (aphA1), streptomycin (strAB), sulphonamides (sul2), tetracycline (tetA(B)) and trimethoprim (dfrA14), as well as mercuric ions (mer genes). In addition, putative virulence-associated genes coding for iron uptake (iutA/iucABCD, sitABCD, and a putative high-affinity Fe²⁺ uptake system) and for a toxin/antitoxin system (vagCD) were identified on the plasmid. All antibiotic and heavy metal resistance genes are located either on class 1 (Tn10-remnant, Tn4352B) and class 2 transposons (Tn2-remnant, Tn21, Tn402-remnant) or a class 1 integron, whereas almost all putative virulence genes are associated with IS elements (IS1, IS26), indicating that transposition and/or recombination events were responsible for acquisition of the accessory pRSB225 modules. Particular modules of plasmid pRSB225 are related to corresponding segments of different virulence plasmids harboured by pathogenic Escherichia coli strains. Moreover, pRSB225 modules were also detected in entero-aggregative-haemorrhagic E. coli (EAHEC) draft genome sequences suggesting that IncF plasmids related to pRSB225 mediated gene transfer into pathogenic E. coli derivatives.
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Salazar CO, Cardenas VM, Reddy RK, Dominguez DC, Snyder LK, Graham DY. Greater than 95% success with 14-day bismuth quadruple anti- Helicobacter pylori therapy: a pilot study in US Hispanics. Helicobacter 2012; 17:382-90. [PMID: 22967122 DOI: 10.1111/j.1523-5378.2012.00962.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND A combination capsule of bismuth, metronidazole, and tetracycline plus omeprazole given as 10-day therapy has an overall effectiveness of 92-93% in per-protocol analysis (Grade B) with eradication of 86-91% of metronidazole-resistant Helicobacter pylori. This study aimed to explore whether extending the duration to 14 days would improve overall effectiveness per protocol to ≥95% (Grade A) in a population in which metronidazole resistance was anticipated to exist. METHODS A one-arm, open-label pilot study of H. pylori-infected, asymptomatic/mildly dyspeptic adults, Hispanic residents of El Paso, Texas, received a 14-day course of omeprazole, plus the combination capsule. We cultured and Gram-stained specimens obtained using a minimally invasive orogastric brush. Helicobacter pylori status was determined by (13)C-urea breath test at 4 or more weeks post-therapy. RESULTS Forty-seven subjects (7 men and 40 women, average age 42 years) were entered. The per-protocol effectiveness was 97.1% (33/34) (95% mid-P CI: 86.3, 99.9); 100% of metronidazole-resistant strains were eradicated. Side effects were mild and self-limited but contributed to nonadherence. Therapy taken for <10 days was more likely to result in eradication failure (p < .001). Office-based orogastric brushing was well tolerated; positive cultures were obtained in 95%. Gram staining showed H. pylori-like forms in all specimens. CONCLUSIONS This pilot study supports the concept that 14-day OBMT therapy is likely to be more efficacious for H. pylori eradication (Grade A, PP basis) than a 10-day course where metronidazole resistance is suspected. If confirmed, 14 days should be recommended in populations where metronidazole resistance is common.
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Affiliation(s)
- Cesar O Salazar
- University of Texas-Houston School of Public Health, El Paso Regional Campus, El Paso, TX 79902, USA
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Nguyen TVH, Bengtsson C, Yin L, Nguyen GK, Hoang TTH, Phung DC, Sörberg M, Granström M. Eradication of Helicobacter pylori in children in Vietnam in relation to antibiotic resistance. Helicobacter 2012; 17:319-25. [PMID: 22759333 DOI: 10.1111/j.1523-5378.2012.00950.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Low Helicobacter pylori eradication rates are common in pediatric trials especially in developing countries. The aim of the study was to investigate the role of antibiotic resistance, drug dosage, and administration frequency on treatment outcome for children in Vietnam. MATERIALS AND METHODS Antibiotics resistance of H. pylori was analyzed by the Etest in 222 pretreatment isolates from children 3-15 years of age who were originally recruited in a randomized trial with two treatment regiments: lansoprazole with amoxicillin and either clarithromycin (LAC) or metronidazole (LAM) in two weight groups with once- or twice-daily administration. The study design was an observational study embedded in a randomized trial. RESULTS The overall resistance to clarithromycin, metronidazole, and amoxicillin was 50.9%, 65.3%, and 0.5%, respectively. In LAC, eradication was linked to the strains being susceptible to clarithromycin (78.2% vs 29.3%, p = .0001). Twice-daily dosage of proton-pump inhibitor (PPI) and clarithromycin was more effective for eradication than once-daily dosage for resistant strains (50.0% vs 14.7%, p = .004) and tended to be so also for sensitive strains (87.5% vs 65.2%, p = .051). Exact antibiotic dose per body weight resulted in more eradication for resistant strains (45.3% vs 8.0%, p = .006). These differences were less pronounced for the LAM regimen, with twice-daily PPI versus once daily for resistant strains resulting in 69.2% and 50.0% eradication (p = .096), respectively. CONCLUSIONS Helicobacter pylori clarithromycin resistance was unexpectedly high in young children in Vietnam. Clarithromycin resistance was an important cause for eradication treatment failure. Twice-daily administration and exact antibiotic dosing resulted in more eradicated infections when the strains were antibiotic resistant, which has implications for the study design in pediatric H. pylori eradication trials.
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Affiliation(s)
- Thi Viet Ha Nguyen
- Department of Pediatrics, Hanoi Medical University and National Hospital of Pediatrics, Hanoi, Vietnam
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López-Colombo A. [Are we doing the right thing with Helicobacter pylori?]. REVISTA DE GASTROENTEROLOGIA DE MEXICO 2012; 77:106-107. [PMID: 22921102 DOI: 10.1016/j.rgmx.2012.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2012] [Accepted: 06/30/2012] [Indexed: 06/01/2023]
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Khan A, Farooqui A, Manzoor H, Akhtar SS, Quraishy MS, Kazmi SU. Antibiotic resistance and cagA gene correlation: A looming crisis of Helicobacter pylori. World J Gastroenterol 2012; 18:2245-52. [PMID: 22611319 PMCID: PMC3351776 DOI: 10.3748/wjg.v18.i18.2245] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2011] [Revised: 12/06/2011] [Accepted: 03/10/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine antibiotic resistance of Helicobacter pylori (H. pylori) in Pakistan and its correlation with host and pathogen associated factors.
METHODS: A total of 178 strains of H. pylori were isolated from gastric biopsies of dyspeptic patients. Susceptibility patterns against first and second-line antibiotics were determined and trends of resistance were analyzed in relation to the sampling period, gastric conditions and cagA gene carriage. The effect of cagA gene on the acquisition of resistance was investigated by mutant selection assay.
RESULTS: The observations showed that monoresistant strains were prevalent with rates of 89% for metronidazole, 36% for clarithromycin, 37% for amoxicillin, 18.5% for ofloxacin and 12% for tetracycline. Furthermore, clarithromycin resistance was on the rise from 2005 to 2008 (32% vs 38%, P = 0.004) and it is significantly observed in non ulcerative dyspeptic patients compared to gastritis, gastric ulcer and duodenal ulcer cases (53% vs 20%, 18% and 19%, P = 0.000). On the contrary, metronidazole and ofloxacin resistance were more common in gastritis and gastric ulcer cases. Distribution analysis and frequencies of resistant mutants in vitro correlated with the absence of cagA gene with metronidazole and ofloxacin resistance.
CONCLUSION: The study confirms the alarming levels of antibiotic resistance associated with the degree of gastric inflammation and cagA gene carriage in H. pylori strains.
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Milani M, Ghotaslou R, Akhi MT, Nahaei MR, Hasani A, Somi MH, Rafeey M, Sharifi Y. The status of antimicrobial resistance of Helicobacter pylori in Eastern Azerbaijan, Iran: comparative study according to demographics. J Infect Chemother 2012; 18:848-52. [PMID: 22581031 DOI: 10.1007/s10156-012-0425-4] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2012] [Accepted: 04/18/2012] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori-associated infections are extremely common in Iran, but few data about antibiotic sensitivity of H. pylori are available for this region. The purpose of this study was to investigate the prevalence of resistance in isolates against commonly used antibiotics in Eastern Azerbaijan, Iran, and the dependence of prevalence on the sex and age of patients. H. pylori isolates were collected by culture from gastric biopsies. Antibiotic susceptibility of isolates was determined by use of the disk agar diffusion test, and the minimum inhibitory concentration of clarithromycin was established by use of the Etest. A total 395 of biopsy specimens were studied; 112 samples of H. pylori were isolated (28.3 %), 55 (49 %) from males and 57 (51 %) from females. The prevalence of resistance to clarithromycin, metronidazole, erythromycin, amoxicillin, ciprofloxacin, rifampin, nitrofurantoin, and tetracycline were 16 (14.3 %), 86 (76.8 %), 29 (26.0 %), 32 (28.6 %), 37 (33.0 %), 32 (28.6 %), 13 (11.6 %), and 21 (18.7 %), respectively. Antimicrobial resistance was not statistically significantly associated with sex or age. Furthermore, the prevalence of resistance to metronidazole was high and that to clarithromycin was reasonable, consistent with reported low success in H. pylori treatment in this area. Therefore, continuous surveillance of antibiotic resistance of H. pylori is essential.
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Affiliation(s)
- Morteza Milani
- Liver and Gastroenterology Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Melake NA, Shaker GH, Salama MA. Incidence of Helicobacter pylori infection and their clarithromycin-resistant strains in otitis media with effusion regarding phenotypic and genotypic studies. Saudi Pharm J 2012; 20:345-53. [PMID: 23960809 DOI: 10.1016/j.jsps.2012.02.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2011] [Accepted: 02/19/2012] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori (H. pylori) are pathogenic bacteria that infect a half of the human population, colonize gastric mucosa and can be found in gastric juice. Reflux of gastric juice has been suggested to be associated with glue ear in children. It has been suggested that tonsil and adenoid tissues are potential reservoirs of H. pylori infection. These observations raise the question as to whether H. pylori infection might have a role in otitis media with effusion (OME) in children. The objectives of this research were to evaluate the incidence and possible role of H. pylori in the pathogenesis of OME in children and to evaluate the clarithromycin-resistant strains. Molecular assessment was done to evaluate the culture results vs. molecular study. A total of 60 children, who were prone to ventilation tube insertion, adenoidectomy and/or tonsillectomy were included in the study. The control group consisted of 40 children who underwent adenoidectomy and/or tonsillectomy without the history of OME. Samples of the middle ear fluid and mucosa, adenoid tissue, tonsillar tissue and gastric lavage were cultured and underwent polymerase chain reaction (PCR) analysis then were assembled by using QIAxcel System as capillary electrophoresis for H. pylori detection. There was significant difference between the results of cultures and PCR (P < 0.05). Middle ear fluid culture was positive for H. pylori in 40% of the patients vs. 56.7% PCR results while middle ear mucosa culture was positive in 20% vs. 26.7% PCR results. Gastric lavage culture was positive in 46.6% of the patients and PCR was positive in 63.3% of the patients. Adenoid culture and PCR were positive in 56.3% for each, while tonsil culture was positive in 70% and PCR was positive in 90%. H. pylori presence in the gastric lavage, the tonsillar and adenoid tissues by culture and PCR was significantly more frequent in the study group compared to the control group. The minimum inhibitory concentration (MIC) values of clarithromycin-resistant isolates ranged from 1.5 to 8 μg/ml. This study showed the presence of H. pylori in around 50% of the patients with OME. PCR revealed its sensitivity than culture techniques. The incidence of clarithromycin resistance was found to be high among the isolates (39.6%).
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Affiliation(s)
- Nahla A Melake
- Department of Pharmaceutics-Microbiology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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Liu G, Xu X, He L, Ding Z, Gu Y, Zhang J, Zhou L. Primary antibiotic resistance of Helicobacter pylori isolated from Beijing children. Helicobacter 2011; 16:356-62. [PMID: 21923681 DOI: 10.1111/j.1523-5378.2011.00856.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The antimicrobials resistance of Helicobacter pylori (H. pylori) was able to sharply decline the eradication rate of H. pylori both in adults and children, but there are limited studies about the primary antibiotic resistance and the related gene mutations, specifically in China. MATERIALS AND METHODS The primary resistance to 9 antibiotics of 73 H. pylori strains isolated from gastric biopsies of children recruited at Beijing Children's Hospital was assessed, and the mutations in 23S rRNA gene of 65 macrolide-resistant strains and in gyrA and gyrB of 12 quinolone-resistant strains were investigated. RESULTS The resistance rate to clarithromycin, azithromycin, metronidazole, levofloxacin, moxifloxacin, and rifampicin was 84.9%, 87.7%, 61.6%, 13.7%, 15.1%, and 6.8%, respectively. No resistance to amoxicillin, gentamicin, and tetracycline was observed. Dual, triple, and quadruple antibacterial resistant percentage was 46.6% (34/73), 15.1% (11/73), and 2.7% (2/73), respectively. The gene mutation rate of A2142C, A2142G, and A2143G in 23S rRNA gene was 1.5% (1/65), 6.2% (4/65), and 84.6% (55/65), respectively. The detection rate of mutations of Asn87, Asp91, and Met191 in GyrA was 41.7% (5/12), 25% (3/12), and 25% (3/12), respectively. CONCLUSION The high prevalence of primary antibiotic resistance was out of expectation in H. pylori strains isolated from the children in Beijing. Antibiotic susceptibility should be made clear before the antibiotic was used in the anti-H. pylori therapy in this population. The A2143G was the most populated mutation in macrolide-resistant strains, and Asn87 and Asp91 of GyrA were the most common mutation points in quinolone resistance strains.
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Affiliation(s)
- Guodong Liu
- National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
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Greenberg ER, Anderson GL, Morgan DR, Torres J, Chey WD, Bravo LE, Dominguez RL, Ferreccio C, Herrero R, Lazcano-Ponce EC, Meza-Montenegro MM, Peña R, Peña EM, Salazar-Martínez E, Correa P, Martínez ME, Valdivieso M, Goodman GE, Crowley JJ, Baker LH. 14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: a randomised trial. Lancet 2011; 378:507-14. [PMID: 21777974 PMCID: PMC3313469 DOI: 10.1016/s0140-6736(11)60825-8] [Citation(s) in RCA: 204] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Evidence from Europe, Asia, and North America suggests that standard three-drug regimens of a proton-pump inhibitor plus amoxicillin and clarithromycin are significantly less effective for eradication of Helicobacter pylori infection than are 5-day concomitant and 10-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses than do three-drug regimens and thus could be suitable for eradication programmes in low-resource settings. Few studies in Latin America have been done, where the burden of H pylori-associated diseases is high. We therefore did a randomised trial in Latin America comparing the effectiveness of four-drug regimens given concomitantly or sequentially with that of a standard 14-day regimen of triple therapy. METHODS Between September, 2009, and June, 2010, we did a randomised trial of empiric 14-day triple, 5-day concomitant, and 10-day sequential therapies for H pylori in seven Latin American sites: Chile, Colombia, Costa Rica, Honduras, Nicaragua, and Mexico (two sites). Participants aged 21-65 years who tested positive for H pylori by a urea breath test were randomly assigned by a central computer using a dynamic balancing procedure to: 14 days of lansoprazole, amoxicillin, and clarithromycin (standard therapy); 5 days of lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant therapy); or 5 days of lansoprazole and amoxicillin followed by 5 days of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Eradication was assessed by urea breath test 6-8 weeks after randomisation. The trial was not masked. Our primary outcome was probablity of H pylori eradication. Our analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, registration number NCT01061437. FINDINGS 1463 participants aged 21-65 years were randomly allocated a treatment: 488 were treated with 14-day standard therapy, 489 with 5-day concomitant therapy, and 486 with 10-day sequential therapy. The probability of eradication with standard therapy was 82·2% (401 of 488), which was 8·6% higher (95% adjusted CI 2·6-14·5) than with concomitant therapy (73·6% [360 of 489]) and 5·6% higher (-0·04% to 11·6) than with sequential therapy (76·5% [372 of 486]). Neither four-drug regimen was significantly better than standard triple therapy in any of the seven sites. INTERPRETATION Standard 14-day triple-drug therapy is preferable to 5-day concomitant or 10-day sequential four-drug regimens as empiric therapy for H pylori infection in diverse Latin American populations. FUNDING Bill & Melinda Gates Foundation, US National Institutes of Health.
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Affiliation(s)
- E Robert Greenberg
- SWOG Statistical Center, Cancer Research and Biostatistics, Seattle, WA 98101-1468, USA.
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Ayala G, Galván-Portillo M, Chihu L, Fierros G, Sánchez A, Carrillo B, Román A, López-Carrillo L, Silva-Sánchez J. Resistance to antibiotics and characterization of Helicobacter pylori strains isolated from antrum and body from adults in Mexico. Microb Drug Resist 2011; 17:149-55. [PMID: 21303219 DOI: 10.1089/mdr.2010.0154] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND AND AIMS Resistance to antibiotics is common in patients with Helicobacter pylori infection in more than one anatomic stomach site. We assessed whether the antibiotic resistance varies according to virulence factors of the bacteria as well as to the age and gender of individuals infected in two anatomic sites. METHODS H. pylori strains were isolated from an antral and corpus biopsy from 90 patients with gastric ambulatory who had not received any previous therapy. Susceptibility to metronidazole and clarithromycin was assessed by E-test, and vacA and cagA genotypes were determined by polymerase chain reaction. RESULTS Dual resistance to metronidazole and clarithromycin was 3.3% in antrum and 4.4% in the corpus; heteroresistance was 19% and 5.5% for metronidazole and clarithromycin, respectively. Clarithromycin resistance significantly increased with age. Women showed a twofold increased risk for metronidazole-resistant strains in antrum (odds ratio = 2.85, 95% confidence interval 1.09 to 7.42). Virulence factors were not associated with antimicrobial resistance. CONCLUSION Prevalence of resistance to clarithromycin may be increasing in this country. Antimicrobial susceptibility tests from different biopsy sites deserve attention.
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Affiliation(s)
- Guadalupe Ayala
- Instituto Nacional de Salud Pública, SSA, Cuernavaca, Morelos, Mexico
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Ahmad N, Zakaria WR, Mohamed R. Analysis of antibiotic susceptibility patterns of Helicobacter pylori isolates from Malaysia. Helicobacter 2011; 16:47-51. [PMID: 21241412 DOI: 10.1111/j.1523-5378.2010.00816.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The prevalence of antibiotic resistance varies in geographic areas. The information on the antibiotic susceptibility patterns of Helicobacter pylori (H. pylori) in our local setting is therefore relevant as a guide for the treatment options. OBJECTIVE This study was conducted to determine the primary resistance rates among H. pylori isolated from Malaysian patients. MATERIALS AND METHODS Biopsy samples were obtained from the stomach antrum and corpus of 777 patients from September 2004 until 2007. H. pylori isolated from these patients were then subjected to minimum inhibitory concentration (MICs) determination using E-test method, against metronidazole, clarithromycin, levofloxacin, ciprofloxacin, amoxicillin, and tetracycline. RESULTS From 777 patients, 119 were positive for H. pylori where a total of 187 strains were isolated. The resistance rates were noted to be 37.4% (metronidazole), 2.1% (clarithromycin), 1% (levofloxacin and ciprofloxacin), and 0% (amoxicillin and tetracycline). Different resistance profiles were observed among isolates from the antrum and corpus of 13 patients. Resistance to one type of antibiotic was observed in 36.4% of the strains where mono-resistance to metronidazole was the most common. Resistance to ≥2 antibiotics was noted in 3.3% of isolates. High metronidazole MICs of ≥256 μg/mL were observed among the resistant strains. CONCLUSIONS The resistance rates of the antibiotics used in primary treatment of H. pylori infections in Malaysia are low, and multi-antibiotic-resistant strains are uncommon. Infections with mixed populations of metronidazole-sensitive and -resistant strains were also observed. However, the high metronidazole MIC values seen among the metronidazole-resistant strains are a cause for concern.
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Affiliation(s)
- Norazah Ahmad
- Bacteriology Unit, Institute for Medical Research, Jalan Pahang, 50588, Kuala Lumpur, Malaysia.
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Koizumi W, Tanabe S, Nakatani K, Ishido K, Nishimura K, Azuma M, Ae T, Sasaki T, Higuchi K, Katada C, Nakayama N, Saigenji K. Quadruple therapy with ecabet sodium, omeprazole, amoxicillin and metronidazole is effective for eradication of Helicobacter pylori after failure of first-line therapy (KDOG0201 Study). J Clin Pharm Ther 2010; 35:303-7. [PMID: 20831531 DOI: 10.1111/j.1365-2710.2009.01092.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND AND OBJECT An antiulcer agent, ecabet sodium, is active against Helicobacter pylori. The aim of the present study was to clinically examine whether eradication therapy, which includes ecabet sodium, is effective in eradication of H. pylori after failure of first-line therapy. METHODS Patients with peptic ulcer who failed with first-line triple eradication therapy containing clarithromycin received quadruple therapy with omeprazole (20 mg, twice daily), amoxicillin (750 mg, twice daily), metronidazole (500 mg, twice daily) and ecabet sodium (1000 mg, twice daily) for 14 days. Eradication of H. pylori was judged by 13C-urea breath test 8 weeks later. RESULTS Fifty-two patients (36 men and 16 women) were included. Their mean age was 51.4 years (range 28-73). One patient dropped out because of diarrhoea. The eradication rate was 98.0% (50/51) according to the per-protocol analysis and 96.2% (50/52) according to the intention-to-treat analysis. Side effects occurred in seven patients, but none were serious. CONCLUSIONS Quadruple therapy including ecabet sodium is useful as second-line eradication treatment for H. pylori.
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Affiliation(s)
- W Koizumi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara-shi, Japan.
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Abstract
INTRODUCTION Helicobacter pylori eradication rates have fallen considerably in recent years. Antibiotic resistance is thought to be rising. OBJECTIVES To examine the levels of resistance to metronidazole (MTZ) and clarithromycin (CLA) in H. pylori, isolates were taken in a reference centre in Ireland from 2007 to 2008 and were compared to a similar cohort from a study in 1997. METHOD Antimicrobial susceptibilities were tested by E-test. Frequencies of spontaneous metronidazole and clarithromycin resistance were measured on an agar plate containing the antibiotics at concentrations of 2x and 4x minimum inhibition concentration values. Clinical data were obtained from charts, laboratory and endoscopy reports. RESULTS Two hundred and twenty-two patients were analyzed, 98 were females. Colonies amenable to culture were grown in 219 patients. Thirty-seven had prior attempts at eradication therapy (all with amoxicillin-CLA-proton pump inhibitor. A total of 31.5% of the patients had strains resistant to MTZ and 13.2% of the patients were noted to have strains resistant to CLA. About 8.6% of the patients had strains resistant to both the agents. CLA resistance was 9.3% in those who had no prior eradication therapy compared with 32.4% of those who had. CLA resistance increased from 3.9%, among treatment-naive patients in 1997, to 9.3% in our study. MTZ resistance was 29.1% in the treatment-naive population. In 1997, MTZ resistance in the treatment-naive cohort was 27.1%. MTZ resistance was more likely to occur in females (35.4 vs. 28.5%) than in males. CONCLUSION This study shows that resistance to CLA among Irish patients infected with H. pylori has increased since 1997. The future of treatment may well lie in the widespread use of sensitivity testing before the treatment. This would promote an accurate treatment.
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Ben Mansour K, Burucoa C, Zribi M, Masmoudi A, Karoui S, Kallel L, Chouaib S, Matri S, Fekih M, Zarrouk S, Labbene M, Boubaker J, Cheikh I, Hriz MB, Siala N, Ayadi A, Filali A, Mami NB, Najjar T, Maherzi A, Sfar MT, Fendri C. Primary resistance to clarithromycin, metronidazole and amoxicillin of Helicobacter pylori isolated from Tunisian patients with peptic ulcers and gastritis: a prospective multicentre study. Ann Clin Microbiol Antimicrob 2010; 9:22. [PMID: 20707901 PMCID: PMC2928169 DOI: 10.1186/1476-0711-9-22] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2010] [Accepted: 08/13/2010] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The frequency of primary resistance to antibiotics in H. pylori isolates is increasing worldwide. In Tunisia, there are limited data regarding the pattern of H. pylori antibiotic primary resistance. AIM To evaluate the primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin and to detect the mutations involved in clarithromycin resistance. MATERIALS AND METHODS 273 strains isolated from adults and children were enrolled. The primary resistance to clarithromycin, metronidazole and amoxicillin was evaluated by means of E-test minimal inhibitory concentration (MIC). The real-time PCR using Scorpion primers was performed in all cases to assess clarithromycin primary resistance and point mutations involved. RESULTS No resistance to amoxicillin was detected. For adults, resistance to clarithromycin and metronidazole was found respectively in 14.6% and 56.8%, and respectively in 18.8% and 25% in children. Overall, the rates of global primary resistance to clarithromycin and metronidazole in Tunisia were respectively determined in 15.4% and 51.3%.By the use of Scorpion PCR, the A2143G was the most frequent point mutation observed (88.1%), followed by the A2142G (11.9%); the A2142C was not found and 18 of 42 patients (42.8%) were infected by both the resistant and the susceptible genotype.The association of clarithromycin resistance with gender was not statistically significant, but metronidazole resistant strains were isolated more frequently in females (67.8%) than in males (32.2%) and the difference was significant. As for gastroduodenal diseases, the difference between strains isolated from patients with peptic ulceration and those with non peptic ulceration was not statistically significant. When about the distribution of resistant strains to clarithromycin and metronidazole between the three Tunisian cities (Tunis, Menzel Bourguiba and Mahdia), the difference was not statistically significant. CONCLUSION Local data regarding the primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin and the main genetic mutation involved in clarithromycin resistance in vivo (A2143G) are necessary to prove a clear need for a periodic evaluation of antibiotic consumption and new therapeutic strategies in Tunisia in order to avoid the emergence of resistant strains.
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Affiliation(s)
- Khansa Ben Mansour
- Microbiology laboratory/UR04SP08 Rabta University Hospital-Tunis, 1007 El Jabbari, Tunisia.
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Abstract
Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcers and gastric cancer. H. pylori eradication has been shown to have a prophylactic effect against gastric cancer. According to several international guidelines, the first-line therapy for treating H. pylori infection consists of a proton pump inhibitor (PPI) or ranitidine bismuth citrate, with any two antibiotics among amoxicillin, clarithromycin and metronidazole, given for 7-14 days. However, even with these recommended regimens, H. pylori eradication failure is still seen in more than 20% of patients. The failure rate for first-line therapy may be higher in actual clinical practice, owing to the indiscriminate use of antibiotics. The recommended second-line therapy is a quadruple regimen composed of tetracycline, metronidazole, a bismuth salt and a PPI. The combination of PPI-amoxicillin-levofloxacin is a good option as second-line therapy. In the case of failure of second-line therapy, the patients should be evaluated using a case-by-case approach. European guidelines recommend culture before the selection of a third-line treatment based on the microbial antibiotic sensitivity. H. pylori isolates after two eradication failures are often resistant to both metronidazole and clarithromycin. The alternative candidates for third-line therapy are quinolones, tetracycline, rifabutin and furazolidone; high-dose PPI/amoxicillin therapy might also be promising.
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Affiliation(s)
- Hidekazu Suzuki
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
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Broussard CS, Goodman KJ, Nurgalieva ZZ, Fischbach LA, Gold BD. Exposure to antibiotics in a United States-Mexico border birth cohort. Pediatrics 2010; 125:e1468-74. [PMID: 20457685 DOI: 10.1542/peds.2008-3173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVE The goal was to compare the frequency of children's antibiotic intake, emphasizing antibiotics with anti-Helicobacter pylori effects, in El Paso, Texas, and Juarez, Mexico. METHODS Hispanic children were enrolled prenatally at mother-child clinics in El Paso, and Juarez, in 1998-2000, to identify determinants of H pylori infection. During follow-up examinations targeted every 6 months from 6 to 84 months of age, caretakers reported medication use during the preceding interval. Courses of any systemic and H pylori-effective antibiotics were compared for US and Mexican children. RESULTS Antibiotic data were available for 602 children, from 2938 follow-up visits. Overall antibiotic intake was higher in Juarez, where 84% of children received > or = 1 course during the follow-up period (52% of visits), compared with El Paso, where 76% of children received > or = 1 course (40% of visits). In contrast, the intake of H pylori-effective antibiotics was higher in El Paso, where 65% of children received > or = 1 course during the follow-up period (27% of visits), compared with Juarez, where 44% of children received > or = 1 course (16% of visits). Of H pylori-effective courses, 94% contained amoxicillin and 2% each clarithromycin, metronidazole, and furazolidone; uses were primarily for throat and ear infections, diarrhea, and cold/flu. CONCLUSIONS Pediatric antibiotic use was higher in Mexico than on the US side of the border. Apparent misuse of H pylori-effective antibiotics was more frequent in Juarez but also occurred in El Paso. Such misuse of antibiotics may lead to drug resistance and may impair the control of H pylori infection in this region.
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Affiliation(s)
- Cheryl S Broussard
- School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
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Alfaresi MS, Elkoush AA. Characterization of clarithromycin resistance in isolates of Helicobacter pylori from the UAE. Indian J Gastroenterol 2010; 29:116-20. [PMID: 20658326 DOI: 10.1007/s12664-010-0034-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2009] [Accepted: 01/07/2010] [Indexed: 02/04/2023]
Abstract
BACKGROUND Clarithromycin therapy is effective in eradicating Helicobacter pylori. However, the resistance of H. pylori to clarithromycin is increasingly reported. The present study aimed to characterize the types of mutations present in the 23S rRNA genes of isolates of clarithromycin-resistant H. pylori from the UAE. METHODS Clarithromycin susceptibility of H. pylori isolates (n = 26) was determined by E tests. Analyses for point mutations in domain V of the 23S rRNA genes in clarithromycin-resistant and-sensitive strains were performed by sequence analysis of amplified PCR products. RESULTS Out of 100 gastric antral biopsy samples, 26 were positive for H. pylori by culture, and 29 were positive by PCR. Of the 26 culture isolates, five (19.2%) were resistant to clarithromycin and 24 were sensitive. The MIC of the resistant strains ranged from 3 to 24 microg/mL (median 24). All of the clarithromycin-resistant isolates had point mutations in the 23S rRNA gene. Two isolates had an A2142G 23S rRNA mutation, and three had A2143G mutations. CONCLUSION Clarithromycin resistance was common in this small collection of H. pylori isolates from the UAE. The A2142G and A2143G mutations were associated with clarithromycin resistance.
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Affiliation(s)
- Mubarak S Alfaresi
- Department of Pathology and Laboratory Medicine, Zayed Military Hospital, Abu Dhabi, United Arab Emirates.
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Ho SL, Tan EL, Sam CK, Goh KL. Clarithromycin resistance and point mutations in the 23S rRNA gene in Helicobacter pylori isolates from Malaysia. J Dig Dis 2010; 11:101-5. [PMID: 20402836 DOI: 10.1111/j.1751-2980.2010.00423.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To determine the prevalence of primary clarithromycin resistance amongst Helicobacter pylori (H. pylori) strains in Malaysian patients with gastroduodenal diseases, by using restriction fragment length polymorphism (RFLP) in domain V of 23S rRNA. METHODS Gastric biopsies were obtained from H. pylori positive patients undergoing gastroscopy. DNA extraction was followed by PCR amplification using the primers Hp23-1 and Hp23-2 flanking a region of 425bp within the bacterial 23S rRNA peptidyltranferase (Hp23S fragment). Analysis of the 23S rRNA gene mutations is based on the generation of restriction sites for two restriction enzymes: BbsI and BsaI, which correspond to the base substitutions characteristic of clarithromycin resistance from A to G at positions 2142 and 2143, respectively. RESULTS Gastric biopsy samples were obtained from 107 patients. A fragment of size 425bp corresponding to that expected from amplification of domain V of 23S rRNA was PCR-amplified from only 105 samples. The amplicon was subsequently subjected to restriction by BbsI and BsaI. Only 1 sample (0.95%) had the BbsI mutation (base substitution at A2142G) and 2 samples (1.90%) the BsaI mutation (base substitution at A2143G). Thus 3 of 105 (2.9%) samples harbored clarithromycin resistant strains. CONCLUSION In our experience, PCR-RFLP is a rapid and precise method to detect the resistance of H. pylori to clarithromycin. Using this method, a low prevalence of clarithromycin resistance was detected in our local Malaysian strains. This augurs well for the continued use of clarithromycin as a first line drug in the treatment and eradication of H. pylori infection.
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Affiliation(s)
- Sin-Loong Ho
- Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
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