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Lopera B, Lemos K, Atehortúa JD, Valencia-Cárdenas J, Vélez-Gómez D, Martinez A, Pérez-Cala T, Salazar B. Furazolidone susceptibility of Helicobacter pylori isolated from patients with gastroduodenal diseases in Colombia. Rev Inst Med Trop Sao Paulo 2025; 67:e20. [PMID: 40197963 PMCID: PMC11981076 DOI: 10.1590/s1678-9946202567020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 11/19/2024] [Indexed: 04/10/2025] Open
Abstract
Estimates suggest that over 50% of the global population suffer from Helicobacter pylori infections. Nowadays, first-line quadruple therapy is recommended to eradicate the bacteria due to the increasing failures of the standard triple therapy. Thus, antibiotics such as furazolidone have emerged as a new treatment due to their success rate (>90%) in rescue therapies. Nevertheless, furazolidone is not routinely used for treatment of H. pylori in Colombia. Still, some Asian countries commonly prescribe it. This study aimed to determine the susceptibility of H. pylori to furazolidone in isolates from patients with gastroduodenal diseases in Colombia that were extracted from 2019-2022. A descriptive study was carried out with 179 patients with gastroduodenal diseases. Susceptibility was determined by the agar dilution method. The gene oorD from resistant isolates was amplified by polymerase chain reaction, and their PCR products were sequenced. The frequency of H. pylori equaled 23.5% (42/179); the bacterium was isolated in 84 gastric biopsies. Moreover, 1.7% (3/179) of patients had one resistant isolate to furazolidone in at least one of the two gastric biopsies, corresponding to 5.95% (5/84) of the isolates resisting furazolidone. Overall, three new mutations in the oorD gene occurred in one isolate, and two of the mutations in the five isolates had been reported in Iran, Brazil, and China. This research found low in vitro resistance of H. pylori isolates to furazolidone in Colombia. Finally, all five isolates showed mutations in the oorD gene.
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Affiliation(s)
- Brandonn Lopera
- Universidad de Antioquia, Escuela de Microbiología, Medellín, Colombia
| | - Kellys Lemos
- Universidad de Antioquia, Escuela de Microbiología, Medellín, Colombia
| | - José Danilo Atehortúa
- Universidad de Antioquia, Facultad de Medicina, Departamento de Microbiología y Parasitología, Grupo Bacterias & Cáncer, Medellín, Colombia
| | | | - Diego Vélez-Gómez
- Universidad de Antioquia, Facultad de Medicina, Departamento de Microbiología y Parasitología, Grupo Bacterias & Cáncer, Medellín, Colombia
| | - Alonso Martinez
- Universidad de Antioquia, Facultad de Medicina, Departamento de Microbiología y Parasitología, Grupo Bacterias & Cáncer, Medellín, Colombia
| | - Tania Pérez-Cala
- Universidad de Antioquia, Facultad de Medicina, Departamento de Microbiología y Parasitología, Grupo Bacterias & Cáncer, Medellín, Colombia
| | - Beatriz Salazar
- Universidad de Antioquia, Facultad de Medicina, Departamento de Microbiología y Parasitología, Grupo Bacterias & Cáncer, Medellín, Colombia
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Wang H, Wei W, Liu F, Wang M, Zhang Y, Du S. Effects of fucoidan and synbiotics supplementation during bismuth quadruple therapy of Helicobacter pylori infection on gut microbial homeostasis: an open-label, randomized clinical trial. Front Nutr 2024; 11:1407736. [PMID: 39010853 PMCID: PMC11246856 DOI: 10.3389/fnut.2024.1407736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 06/18/2024] [Indexed: 07/17/2024] Open
Abstract
Background The eradication regimen for Helicobacter pylori (H. pylori) infection can induce gut dysbiosis. In this open-label, prospective, and randomized clinical trial, we aimed to assess the effects of fucoidan supplementation on the eradication rate and gut microbial homeostasis in the context of quadruple therapy, as well as to investigate the combined effects of fucoidan and synbiotics supplementations. Methods Eighty patients with H. pylori infection were enrolled and randomly assigned to one of four treatment groups: the QT (a 2-week quadruple therapy alone), QF (quadruple therapy plus a 6-week fucoidan supplementation), QS (quadruple therapy plus a 6-week synbiotics supplementation), and QFS (quadruple therapy with a 6-week fucoidan and synbiotics supplementation), with 20 patients in each group. The QT regimen included rabeprazole, minocycline, amoxicillin, and bismuth potassium citrate. The synbiotics supplementation contained three strains of Bifidobacterium, three strains of Lactobacillus, along with three types of dietary fiber. All of the patients underwent 13C-urea breath test (13C-UBT) at baseline and at the end of the 6th week after the initiation of the interventions. Fresh fecal samples were collected at baseline and at the end of the 6th week for gut microbiota analysis via 16S rRNA gene sequencing. Results The eradication rates among the four groups showed no significant difference. In the QT group, a significant reduction in α-diversity of gut microbiota diversity and a substantial shift in microbial composition were observed, particularly an increase in Escherichia-Shigella and a decrease in the abundance of genera from the Lachnospiraceae and Ruminococcaceae families. The Simpson index was significantly higher in the QF group than in the QT group. Neither the QS nor QFS groups exhibited significant changes in α-diversity or β-diversity. The QFS group was the only one that did not show a significant increase in the relative abundance of Escherichia-Shigella, and the relative abundance of Klebsiella significantly decreased in this group. Conclusion The current study provided supporting evidence for the positive role of fucoidan and synbiotics supplementation in the gut microbiota. The combined use of fucoidan and synbioticss might be a promising adjuvant regimen to mitigate gut dysbiosis during H. pylori eradication therapy.
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Affiliation(s)
- Huifen Wang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Wei Wei
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
- Department of Clinical Nutrition, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Fang Liu
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Miao Wang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Yanli Zhang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Shiyu Du
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
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Wang JY, Zhou XZ, Wang CJ, Xu SH, Zhu HY, Du YQ. Helicobacter pylori antibiotic resistance in different regions of China: A systematic review and meta-analysis. Shijie Huaren Xiaohua Zazhi 2024; 32:71-87. [DOI: 10.11569/wcjd.v32.i1.71] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 12/06/2023] [Accepted: 01/11/2024] [Indexed: 01/26/2024] Open
Abstract
BACKGROUND Increasing drug resistance of Helicobacter pylori (H. pylori) in China has become one of the major obstacles to the efficacy of empirical eradication therapy. Resistance profiles vary from region to region, which poses an additional challenge to the expansion of empirical eradication therapy.
AIM To evaluate H. pylori antibiotic resistance in various regions of China systematically.
METHODS A thorough computerized search of various databases, including PubMed, EMBASE, Web of Science, Sinomed, CNKI, Wanfang Data, and VIP, was conducted to identify cross-sectional studies on H. pylori resistance in various regions of China. Two researchers independently screened the literature, extracted the data, and evaluated the quality of the literature. R 4.3.1 software was used for Meta-analysis of the resistance rate to each antibiotic and their combinations.
RESULTS A total of 46 eligible articles were included. Clarithromycin (CLA), levofloxacin (LEV), amoxicillin (AMX), tetracycline (TET), metronidazole (MNZ), and furazolidone (FZD) resistance rates in China were 27.72% (95% confidence interval [CI]: 23.80%-31.82%), 31.23% (95%CI: 26.62%-36.02%), 3.97% (95%CI: 1.96%-6.65%), 4.01% (95%CI: 1.36%-7.98%), 75.30% (95%CI: 70.31%-79.97%), and 0.64% (95%CI: 0.13%-1.53%), respectively. The rate of AMX resistance varied significantly among different regions of China, being the highest in South China (7.15%, 95%CI: 6.16%-76.10%) and the lowest in North China (1.86%, 95%CI: 0.67%-3.64%). CLA resistance in East and Central China, LEV resistance in East and Northwest China, and MNZ resistance in North and Southwest China all increased significantly over time, while AMX and TET resistance in East China notably decreased. CLA + MNZ, LEV + MNZ, and CLA + LEV dual resistance rates in China reached 14.05% (95%CI: 10.70%-17.77%), 15.12% (95%CI: 11.53%-19.10%), and 5.16% (95%CI: 2.87%-8.06%), respectively. CLA + LEV + MNZ, LEV + MNZ + AMX, and CLA + MNZ + AMX triple resistance rates were 10.36% (95%CI: 7.45%-13.69%), 0.92% (95%CI: 0.12%-2.44%), and 0.85% (95%CI: 0.20%-1.92%), respectively.
CONCLUSION H. pylori resistance is serious in China, with MNZ resistance rate being the highest, followed by CLA and LEV resistance rates. The detection rate of some multi-resistant organisms has also reached a high level. Antibiotic resistance rates vary slightly across different regions of China, and most of them show an increasing trend over time.
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Affiliation(s)
- Jia-Yue Wang
- Department of Gastroenterology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Xian-Zhu Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Chan-Juan Wang
- Department of Gastroenterology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Shi-Han Xu
- Department of Gastroenterology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Hui-Yun Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Yi-Qi Du
- Department of Gastroenterology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
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Shao Y, Lin Y, Wang B, Miao M, Ye G. Antibiotic resistance status of helicobacter pylori strains isolated from initial eradication patients in Ningbo, China, from 2017 to 2021. Helicobacter 2022; 27:e12920. [PMID: 35939548 DOI: 10.1111/hel.12920] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 07/06/2022] [Accepted: 07/12/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Resistance of Helicobacter pylori (H. pylori) to antibiotics is an evolving and dynamic process. Presence of antibiotic resistance impacts the success rate of initial eradication strategies in the clinic. AIM To improve the success rate of initial eradication therapy and explore new antibiotic regimens, a large sample-based study utilizing antimicrobial susceptibility testing was performed. A total of 2508 H. pylori strains from patients subjected to initial eradication therapy were isolated, cultured, and tested for drug susceptibility from 2017 to 2021. The minimal inhibitory concentration (MIC) was recorded. H. pylori susceptibility profiles and its change trends from initial eradication patients were analyzed. The relationships between drug resistance, year of sample collection, age, and sex of patients were analyzed. RESULTS The overall resistance rates were as follows: amoxicillin (9.25%), clarithromycin (38.48%), levofloxacin (42.86%), furazolidone (11.28%), doxycycline (8.56%), rifampicin (10.81%), tinidazole (74.32%), gatifloxacin (61.71%), tetracycline (0%), metronidazole (78.71%), ornidazole (97.87%), and fosfomycin (31.67%). Only 38.04% of the strains were pansusceptible to amoxicillin, clarithromycin, levofloxacin, and furazolidone, followed by those of mono resistance (29.90%), double resistance (24.96%), triple resistance (6.34%), and quadruple resistance (0.76%). Significant differences in the resistance rate and MIC were also observed in different age and sex groups. Time of collection and patient age and sex were associated with the distribution of antibiotic resistance. CONCLUSION With the increasing resistance rate and multiple resistance of H. pylori to commonly used antibiotics, drug susceptibility testing is imperative to permit individualized therapy, and a regimen containing the combination of amoxicillin, furazolidone, tetracycline, doxycycline, or rifampicin is reasonable for initial empirical eradication therapy.
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Affiliation(s)
- Yongfu Shao
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo, China.,Ningbo University School of Medicine, Ningbo, China
| | - Yifan Lin
- Ningbo University School of Medicine, Ningbo, China
| | - Bojun Wang
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
| | - Min Miao
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
| | - Guoliang Ye
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
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Li H, Shen Y, Song X, Tang X, Hu R, Marshall BJ, Tang H, Benghezal M. Need for standardization and harmonization of Helicobacter pylori antimicrobial susceptibility testing. Helicobacter 2022; 27:e12873. [PMID: 35151236 DOI: 10.1111/hel.12873] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 12/23/2021] [Accepted: 12/27/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIMS As with other infectious diseases, Helicobacter pylori eradication regimens should be guided by susceptibility testing to achieve excellent success rate, especially in the era of high antibiotic resistance. However, susceptibility testing for H. pylori is rarely performed, which can be partly ascribed to the current lack of standardization of testing methods and the lack of unified consensus on the antibiotic resistance breakpoints. The aim of this review was to call for an international consensus on standardization and harmonization of H. pylori susceptibility testing. METHODS We summarize and compare the advantages and disadvantages of four different phenotypic antimicrobial susceptibility testing (AST) methods (agar dilution, E-test, disk diffusion, and broth microdilution) and the molecular susceptibility testing method for H. pylori. RESULTS The standard phenotypic testing methods and the molecular testing methods have their own advantages and disadvantages. Compared to the standard phenotypic methods, the molecular testing method does not require successful H. pylori culture, and therefore, is much more rapid and convenient for clinical use. However, the currently available molecular testing method is only suitable for detecting clarithromycin and quinolone susceptibility profiles in H. pylori. Although the standard AST is time-consuming, it is currently the only way to test the susceptibility of H. pylori to all the commonly used antibiotics. CONCLUSION To make H. pylori susceptibility testing become a clinical routine, an international consensus on standardization and harmonization of H. pylori AST is needed. Future efforts are needed for optimizing broth culture of H. pylori, and developing commercial AST plates for achieving high throughput and automated susceptibility testing for H. pylori.
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Affiliation(s)
- Hong Li
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Yalin Shen
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaona Song
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoqiong Tang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Renwei Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Barry James Marshall
- Helicobacter pylori Research Laboratory, School of Biomedical Sciences, Marshall Centre for Infectious Disease Research and Training, University of Western Australia, Nedlands, Australia
| | - Hong Tang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Mohammed Benghezal
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
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Dai J, Zhao J, Mao L, Hu Y, Lv B. Study on the value of antibiotic-resistant gene detection in Helicobacter pylori in China. Exp Ther Med 2022; 23:228. [PMID: 35222705 PMCID: PMC8815056 DOI: 10.3892/etm.2022.11153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 11/03/2021] [Indexed: 11/05/2022] Open
Abstract
The aim of the present study was to explore the value of detecting antibiotic-resistant genes in Helicobacter pylori (H. pylori) and the association between genotype and antibiotic resistance. Two gastric mucosa samples from each H. pylori-positive patient were collected. Each patient's H. pylori sample was cultured in vitro, and the agar plate dilution method was conducted. In addition, all patient samples were analyzed for the detection of antibiotic resistance-related mutant genes and VacA gene genotypes. The association between VacA genotypes and antibiotic resistance was also determined and the value of mutant gene detection in predicting H. pylori resistance to antibiotics was evaluated. In total, 133 H. pylori-positive patients were enrolled. A total of 22 strains of H. pylori failed to grow in in vitro culture and 25 strains were negative in a H. pylori gene test. Among 108 strains detected by PCR, a total of 39 VacA s1m1 strains, 69 VacA s1m2 strains and no VacA s2 strain were identified. There was no significant association between VacA genotypes and antibiotic resistance. The mutation rates of G616A in the rdxA gene, T87A, G91A, A91G and G91T in the gyrA gene and A2143G and A2142G in the 23S rRNA gene were 32.1, 32.3, 22.6, 12.9, 6.5, 81.8 and 0.0%, respectively. Among these mutant sites, the mutation coincidence rates were as follows, according to the agar plate dilution method: rdxA G616A (81.8%), gyrA G91T (66.7%), gyrA G91A (54.5%), 23 S rRNA A2143G (49.1%), gyrA T87A (45.5%), gyrA A91G (33.3%), penicillin-binding protein 1 (PBP1) C556G (0.0%), PBP1 A562T (0.0%), PBP1 A562G (0.0%) and 16 S rRNA 926-927 (AT-GT) (0.0%). VacA m subtypes were not associated with H. pylori antibiotic resistance. In conclusion, the present findings suggested that the detection of related mutant genes had a clinical application value in predicting the antibiotic resistance of H. pylori, particularly resistance to clarithromycin and levofloxacin.
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Affiliation(s)
- Jinfeng Dai
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China
| | - Jing Zhao
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China
| | - Liqi Mao
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China
| | - Yue Hu
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China
| | - Bin Lv
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China
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Plotnikova K, Dubenska L, Rydchuk P, Pysarevska S, Rydchuk M, Ivakh S, Yanovych D, Zasadna Z, Plotycya S. Voltammetric determination of 5-nitroimidazole derivatives in honey and HPLC-MS/MS confirmation. JOURNAL OF FOOD MEASUREMENT AND CHARACTERIZATION 2021. [DOI: 10.1007/s11694-021-01214-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Milner E, Stevens B, An M, Lam V, Ainsworth M, Dihle P, Stearns J, Dombrowski A, Rego D, Segars K. Utilizing Probiotics for the Prevention and Treatment of Gastrointestinal Diseases. Front Microbiol 2021; 12:689958. [PMID: 34434175 PMCID: PMC8381467 DOI: 10.3389/fmicb.2021.689958] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 07/05/2021] [Indexed: 12/12/2022] Open
Abstract
Probiotics are heavily advertised to promote a healthy gastrointestinal tract and boost the immune system. This review article summarizes the history and diversity of probiotics, outlines conventional in vitro assays and in vivo models, assesses the pharmacologic effects of probiotic and pharmaceutical co-administration, and the broad impact of clinical probiotic utilization for gastrointestinal disease indications.
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Affiliation(s)
- Erin Milner
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
- Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States
| | - Benjamin Stevens
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Martino An
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Victoria Lam
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Michael Ainsworth
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Preston Dihle
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Jocelyn Stearns
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Andrew Dombrowski
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Daniel Rego
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Katharine Segars
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
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Zhang J, Han C, Lu WQ, Wang N, Wu SR, Wang YX, Ma JP, Wang JH, Hao C, Yuan DH, Liu N, Shi YQ. A randomized, multicenter and noninferiority study of amoxicillin plus berberine vs tetracycline plus furazolidone in quadruple therapy for Helicobacter pylori rescue treatment. J Dig Dis 2020; 21:256-263. [PMID: 32348007 PMCID: PMC7383804 DOI: 10.1111/1751-2980.12870] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 04/23/2020] [Accepted: 04/24/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Helicobacter pylori (H. pylori) infection is closely associated with gastric ulcers and gastric adenocarcinomas. We aimed to assess the efficacy and safety of a quadruple regimen with amoxicillin plus berberine vs tetracycline plus furazolidone in rescue therapy for H. pylori eradication. METHODS We conducted a randomized, open-label, multicenter, noninferiority trial. Patients with previous treatment failures recruited from five centers were randomized (1:1) to receive a regimen with esomeprazole and bismuth plus either berberine and amoxicillin (the BA group) or tetracycline and furazolidone (the TF group) for 14 days. Their H. pylori infection status was confirmed 4-8 weeks after treatment. The primary outcome was the eradication rate. The secondary outcomes included the rates of symptom improvement, compliance, and adverse events. This study was registered at ClinicalTrials.gov (NCT03609892). RESULTS Altogether 658 participants were consecutively enrolled. An intention-to-treat analysis demonstrated that the two regimens achieved a similar eradication rate (76.3% vs 77.5%; P = 0.781). The per-protocol analysis reached a similar result (81.5% vs 85.0%; P = 0.278). The eradication rate reached in the BA group was greater than the pre-established margin of noninferiority, at -10% (the lower bounds of the 95% CI were -7.66% and -9.43%, respectively). The rate of adverse events was lower for the BA group than the TF group (18.5% vs 26.1%, P = 0.024). Rates of compliance and symptom improvement were similar for the two therapies. CONCLUSION The efficacy of both regimens in rescue treatment for H. pylori eradication was satisfactory, 14-day BA-based quadruple therapy is noninferior to the TF-based therapy.
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Affiliation(s)
- Jian Zhang
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive DiseasesAir Force Military Medical UniversityXi'anShaanxi ProvinceChina
| | - Chuan Han
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive DiseasesAir Force Military Medical UniversityXi'anShaanxi ProvinceChina,Department of EndocrinologyGeneral Hospital of the Western Theater CommandChengduSichuan ProvinceChina
| | - Wen Quan Lu
- Department of GastroenterologyFirst Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Na Wang
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive DiseasesAir Force Military Medical UniversityXi'anShaanxi ProvinceChina
| | - Si Ran Wu
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive DiseasesAir Force Military Medical UniversityXi'anShaanxi ProvinceChina
| | - Yong Xi Wang
- Department of GastroenterologyXianyang Central HospitalXianyangShaanxi ProvinceChina
| | - Jin Ping Ma
- Department of GastroenterologyXianyang Central HospitalXianyangShaanxi ProvinceChina
| | - Jie Hong Wang
- Department of GastroenterologyAffiliated Hospital of Shaanxi University of Chinese MedicineXianyangShaanxi ProvinceChina
| | - Cheng Hao
- Department of GastroenterologyAffiliated Hospital of Shaanxi University of Chinese MedicineXianyangShaanxi ProvinceChina
| | - Dong Hong Yuan
- Department of GastroenterologyYan'an University Affiliated HospitalYan'anShaanxi ProvinceChina
| | - Na Liu
- Department of GastroenterologySecond Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxi ProvinceChina
| | - Yong Quan Shi
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive DiseasesAir Force Military Medical UniversityXi'anShaanxi ProvinceChina
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Wani FA, Bashir G, Khan MA, Zargar SA, Rasool Z, Qadri Q. Antibiotic resistance in Helicobacter pylori: A mutational analysis from a tertiary care hospital in Kashmir, India. Indian J Med Microbiol 2018; 36:265-272. [PMID: 30084422 DOI: 10.4103/ijmm.ijmm_18_19] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Background Helicobacter pylori infection is recognised as type 1 carcinogen by the International Agency of Research on Cancer. Previous studies in our hospital have revealed high prevalence of H. pylori in our population with a high recurrence rate after completion of treatment. This prompted us to undertake this study. Aim This study aimed to determine common gene mutations leading to resistance to clarithromycin, metronidazole, tetracycline and quinolones in H. pylori in patients attending our hospital. Settings and Design This is a cross-sectional hospital-based study. The study was approved by the Institutional Ethics Committee. Materials and Methods This study was conducted on 196 adult dyspeptic patients with an indication for upper gastrointestinal endoscopy. Gastric biopsies collected from them were subjected to histopathological examination, rapid urease test (RUT) and culture. Of the 196 patients, 95 met the inclusion criteria. Drug susceptibility testing (DST) by various polymerase chain reaction-based methods was done for 47 RUT-positive biopsies and 13 H. pylori isolates. Results Maximum resistance was seen to metronidazole (81.66%) followed by clarithromycin (45%) and quinolones (3.33%). No high-level resistance was seen to tetracycline. In clarithromycin-resistant cases, A2142G mutation was more prevalent than A2143G mutation. Multidrug resistance (resistance to metronidazole and clarithromycin) was seen in 41.66% of patients. Conclusions Tetracycline and quinolones could be the antibiotics of choice in the eradication of H. pylori in this region, while recurrence of the infection with H. pylori could be expected among patients receiving either metronidazole or clarithromycin, for eradication therapy. DST should be done on a routine basis utilising both phenotypic and genotypic methods to prevent further emergence of resistance in this region.
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Affiliation(s)
- Fayaz Ahmad Wani
- Department of Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | - Gulnaz Bashir
- Department of Microbiology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | - Mushtaq Ahmad Khan
- Department of Gastroenterology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | - Showkat Ali Zargar
- Department of Gastroenterology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | - Zubaida Rasool
- Department of Pathology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | - Qurteeba Qadri
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
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11
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Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of Antibiotic Resistance in Helicobacter pylori: A Systematic Review and Meta-analysis in World Health Organization Regions. Gastroenterology 2018; 155:1372-1382.e17. [PMID: 29990487 PMCID: PMC6905086 DOI: 10.1053/j.gastro.2018.07.007] [Citation(s) in RCA: 795] [Impact Index Per Article: 113.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2018] [Revised: 06/27/2018] [Accepted: 07/05/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS In 2017, the World Health Organization (WHO) designated clarithromycin-resistant Helicobacter pylori a high priority for antibiotic research and development. However, there are no clear data on the global distribution of resistance or its clinical effects. We performed a systematic review and meta-analysis to assess the distribution of H pylori resistance to commonly used antibiotics and to measure the association between antibiotic resistance and treatment failure. METHODS We searched publication databases for studies that assessed rates of H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline. Pooled estimates of primary and secondary resistance and 95% confidence intervals (CIs) were grouped by WHO region. The association between antibiotic resistance and treatment failure was measured by extracting data on treatment efficacy in patients with resistant and susceptible isolates and pooling odds ratios with 95% CIs. RESULTS We identified 178 studies, comprising 66,142 isolates from 65 countries. Primary and secondary resistance rates to clarithromycin, metronidazole, and levofloxacin were ≥15% in all WHO regions, except primary clarithromycin resistance in the Americas (10%; 95% CI, 4%-16%) and South-East Asia region (10%; 95% CI, 5%-16%) and primary levofloxacin resistance in the European region (11%; 95% CI, 9%-13%). There was considerable heterogeneity (I2 > 75%) among all analyses-this might have resulted from the grouping of resistance rates by country. Increasing antibiotic resistance was observed in most WHO regions. Resistance to clarithromycin was significantly associated with failure of clarithromycin-containing regimens (odds ratio, 6.97; 95% CI, 5.23-9.28; P < .001). CONCLUSIONS Resistance of H pylori to antibiotics has reached alarming levels worldwide, which has a great effect on efficacy of treatment. Local surveillance networks are required to select appropriate eradication regimens for each region.
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Affiliation(s)
- Alessia Savoldi
- Division of Infectious Diseases, Department of Internal Medicine I, German Center for Infection Research, University of Tübingen, Tübingen, Germany
| | - Elena Carrara
- Division of Infectious Diseases, Department of Diagnostic and Public Health, G.B. Rossi University Hospital, University of Verona, Verona, Italy
| | - David Y Graham
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas
| | - Michela Conti
- Division of Infectious Diseases, Department of Diagnostic and Public Health, G.B. Rossi University Hospital, University of Verona, Verona, Italy
| | - Evelina Tacconelli
- Division of Infectious Diseases, Department of Internal Medicine I, German Center for Infection Research, University of Tübingen, Tübingen, Germany; Division of Infectious Diseases, Department of Diagnostic and Public Health, G.B. Rossi University Hospital, University of Verona, Verona, Italy.
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12
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Zhang YW, Hu WL, Cai Y, Zheng WF, Du Q, Kim JJ, Kao JY, Dai N, Si JM. Outcomes of furazolidone- and amoxicillin-based quadruple therapy for Helicobacter pylori infection and predictors of failed eradication. World J Gastroenterol 2018; 24:4596-4605. [PMID: 30386109 PMCID: PMC6209572 DOI: 10.3748/wjg.v24.i40.4596] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2018] [Revised: 08/16/2018] [Accepted: 10/05/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the outcomes of furazolidone- and amoxicillin-based quadruple therapy for treatment of Helicobacter pylori (H. pylori) infection and identify predictors of failed eradication.
METHODS Patients with H. pylori infection treated with furazolidone, amoxicillin, bismuth, and proton pump inhibitor therapy (January 2015 to December 2015) who received the 13C-urea breath test > 4 wk after treatment were evaluated. Demographic and clinical data including prior H. pylori treatment attempts, medication adherence, alcohol and cigarette consumption during therapy, and treatment-related adverse events were recorded by reviewing medical records and telephone surveys. H. pylori eradication rates for overall and subgroups were evaluated. Multivariate analysis was performed to identify independent predictors of failed H. pylori eradication.
RESULTS Of the 992 patients treated and retested for H. pylori infection, the overall eradication rate was 94.5% [95% confidence interval (CI): 94.1%-95.9%]. H. pylori eradication rate of primary therapy was 95.0% (95%CI: 93.5%-96.5%), while that of rescue therapy was 91.3% (95%CI: 86.8%-95.8%). Among the 859 patients who completed the study protocol, 144 (17%) reported treatment-related adverse events including 24 (3%) leading to premature discontinuation. On multivariate analysis, poor medication adherence [adjusted odds ratio (AOR) = 6.7, 95%CI: 2.8-15.8], two or more previous H. pylori treatments (AOR = 7.4, 95%CI: 2.2-24.9), alcohol consumption during therapy (AOR = 4.4, 95%CI: 1.5-12.3), and possibly smoking during therapy (AOR = 1.9, 95%CI: 0.9-4.3) were associated with failed H. pylori eradication.
CONCLUSION Furazolidone- and amoxicillin-based quadruple therapy for H. pylori infection in an area with a high prevalence of clarithromycin resistance demonstrated high eradication rates as primary and rescue therapies with a favorable safety profile. Patient education targeting abstinence from alcohol during therapy and strict medication adherence may further optimize H. pylori eradication.
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Affiliation(s)
- Ya-Wen Zhang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
- Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Wei-Ling Hu
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
- Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Yuan Cai
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Wen-Fang Zheng
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
- Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Qin Du
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
| | - John J Kim
- Division of Gastroenterology, Loma Linda University, Loma Linda, CA 92354, United States
| | - John Y Kao
- Division of Gastroenterology, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, United States
| | - Ning Dai
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Jian-Min Si
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
- Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
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13
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Salmanroghani H, Mirvakili M, Baghbanian M, Salmanroghani R, Sanati G, Yazdian P. Efficacy and Tolerability of Two Quadruple Regimens: Bismuth, Omeprazole, Metronidazole with Amoxicillin or Tetracycline as First-Line Treatment for Eradication of Helicobacter Pylori in Patients with Duodenal Ulcer: A Randomized Clinical Trial. PLoS One 2018; 13:e0197096. [PMID: 29889843 PMCID: PMC5995362 DOI: 10.1371/journal.pone.0197096] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Accepted: 04/26/2018] [Indexed: 12/22/2022] Open
Abstract
AIM To evaluate the efficacy and tolerability of tetracycline vs. high-dose amoxicillin in bismuth-based quadruple therapy for Helicobacter pylori(H. pylori) eradication. METHODS This randomized, open-label clinical trial included 228 patients with H.pylori infection and duodenal ulcer without a history of H.pylori treatment. Patients were randomly divided into two groups. The amoxicillin group received metronidazole 500mg, bismuth subcitrate 240mg, and amoxicillin 1000mg, all three times a day, plus omeprazole 20 mg twice a day, for 14 days. The tetracycline group received metronidazole 500mg three times a day; bismuth subcitrate240mg and tetracycline HCl 500mg, both four times a day; and omeprazole 20 mg twice a day, for 14 days. Evaluation for compliance and drug-relatedadverse effects were evaluated at the end of two weeks. Eight weeks after the end of treatment, the rate of H.pylori eradication was assessed by the C13urease breath test. RESULTS There were no significant demographic differences between the two groups. Eradication rate was higher with the amoxicillin-containing regimen than the tetracycline-containing regimen: 105/110 (95.51%; 95% confidence interval, 91.5%-99.3%) vs. 88/105 (83.8%; 95%CI, 76.7%-90.8%) by per-protocol analysis (p = 0.005) and 92.9% (95%CI, 88.1%-97.6%) vs. 76.5% (95%CI, 68.7%-84.2%) by intention-to-treat analysis (ITT, p = 0.001). Adverse effects were significant higher in the tetracycline groupthan in the amoxicillin group (65.2% vs. 43.4%; p = 0.001). CONCLUSION Bismuth-based quadruple therapy including high-dose amoxicillin and metronidazole achieved an acceptable rate of H.pylori infection eradication with good tolerance in patients with duodenal ulcer. This regimen can overcome treatment resistance in areas with high prevalence of metronidazole and clarithromycin resistance. TRIAL REGISTRATION The Thai Clinical Trial Registry (TCTR) 20170623004.
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Affiliation(s)
- Hassan Salmanroghani
- Department of Internal Medicine, ShahidSadoughi University of Medical Sciences, Yazd, Iran
- * E-mail:
| | - Massoud Mirvakili
- Department of Internal Medicine, ShahidSadoughi University of Medical Sciences, Yazd, Iran
| | - Mahmud Baghbanian
- Department of Internal Medicine, ShahidSadoughi University of Medical Sciences, Yazd, Iran
| | - Roham Salmanroghani
- Department of Internal Medicine, ShahidSadoughi University of Medical Sciences, Yazd, Iran
| | - Golshid Sanati
- Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Pouria Yazdian
- Department of Internal Medicine, ShahidSadoughi University of Medical Sciences, Yazd, Iran
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Xie Y, Pan X, Li Y, Wang H, Du Y, Xu J, Wang J, Zeng Z, Chen Y, Zhang G, Wu K, Liu D, Lv N. New single capsule of bismuth, metronidazole and tetracycline given with omeprazole versus quadruple therapy consisting of bismuth, omeprazole, amoxicillin and clarithromycin for eradication of Helicobacter pylori in duodenal ulcer patients: a Chinese prospective, randomized, multicentre trial. J Antimicrob Chemother 2018; 73:1681-1687. [PMID: 29596646 DOI: 10.1093/jac/dky056] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Accepted: 01/28/2018] [Indexed: 01/06/2023] Open
Affiliation(s)
- Yong Xie
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Xiaolin Pan
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yan Li
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Huahong Wang
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Yiqi Du
- Department of Gastroenterology, Changhai Hospital of Second Military Medical University, Shanghai, China
| | - Jianming Xu
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Jiangbin Wang
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Zhirong Zeng
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Ye Chen
- Department of Gastroenterology, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, China
| | - Guoxin Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Kaichun Wu
- Department of Gastroenterology, Xijing Hospital of Fourth Military Medical University, Xi’an, Shanxi, China
| | - Dongsheng Liu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Nonghua Lv
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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15
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Efficacy and Safety of Wei Bi Mei, a Chinese Herb Compound, as an Alternative to Bismuth for Eradication of Helicobacter pylori. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:4320219. [PMID: 29636776 PMCID: PMC5832115 DOI: 10.1155/2018/4320219] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Accepted: 01/04/2018] [Indexed: 02/07/2023]
Abstract
Bismuth-containing quadruple therapy has been recommended as the first line of treatment in areas of high clarithromycin or metronidazole resistance. However, safety concerns of bismuth agents have long been raised. We first assessed the efficacy and safety of Wei Bi Mei granules, which are bismuth compounds consisting of three synthetic drugs and five medicinal herbs, compared to bismuth aluminate and colloidal bismuth subcitrate (CBS) in H. pylori-infected mouse model. We then used atomic fluorescence spectroscopy and autometallography to measure the accumulation of three bismuth agents in the brain, heart, liver, and kidneys in adult Sprague-Dawley rats. We also evaluated the safety of bismuth agents by conducting clinical biochemistry tests in blood samples of experimental animals. Wei Bi Mei granules exhibited the highest efficacy of anti-H. pylori activity and yielded the lowest bismuth accumulation when compared to CBS and bismuth aluminate. Our findings show that Wei Bi Mei granules are a safe Chinese medicinal herb with potent anti-H. pylori activity and can be considered as an alternative to current bismuth compounds. Thus, Wei Bi Mei granules merit further evaluation, particularly with regard to efficacy and safety when they are combined with other H. pylori eradication medications in the clinical setting.
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16
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Li H, Liang X, Chen Q, Zhang W, Lu H. Inappropriate treatment in Helicobacter pylori eradication failure: a retrospective study. Scand J Gastroenterol 2018; 53:130-133. [PMID: 29214879 DOI: 10.1080/00365521.2017.1413132] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND In recent years, success rates of empirical H. pylori therapies have fallen in many countries. Although antibiotic resistance and poor adherence are described as the main factors for treatment failure, in China, iatrogenic factors also play an important role. OBJECTIVE To investigate why patients experienced multiple failures, we performed a retrospective, single center study using questionnaires to identify causes of treatment failure other than antibiotic resistance. METHODS This study was conducted from January 2016 to July 2017 in a general hospital. Patients with at least two H. pylori treatment failures who completed the questionnaire were entered. The survey covered characteristics of the study population, regimens used, and adherence to therapy. RESULTS Two hundred and ninety three patients were included in the final analysis. The top three most antibiotic combinations as the first-line treatment were a PPI plus clarithromycin-metronidazole (24.6%, 72/293), clarithromycin-levofloxacin (23.5%, 69/293) and clarithromycin-amoxicillin (21.5%, 63/293). Clarithromycin-containing regimens were repeatedly used in 178 patients (60.8%) and levofloxacin-containing regimens repeatedly in 88 patients (30.0%). Fifty patients (17.1%) had poor adherence per treatment history and 32 (10.9%) stopped treatment because of nonmedical reasons. CONCLUSIONS In order to increase the success of H. pylori eradication therapy, the effect of prior therapies needs to be given more consideration. Patient education to enhance adherence also needs to be improved.
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Affiliation(s)
- Huiyi Li
- a Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health , Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institution of Digestive Disease , Shanghai , China
| | - Xiao Liang
- a Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health , Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institution of Digestive Disease , Shanghai , China
| | - Qi Chen
- a Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health , Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institution of Digestive Disease , Shanghai , China
| | - Wei Zhang
- a Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health , Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institution of Digestive Disease , Shanghai , China
| | - Hong Lu
- a Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health , Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institution of Digestive Disease , Shanghai , China
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17
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Zamani M, Rahbar A, Shokri-Shirvani J. Resistance of Helicobacter pylori to furazolidone and levofloxacin: A viewpoint. World J Gastroenterol 2017; 23:6920-6922. [PMID: 29085236 PMCID: PMC5645626 DOI: 10.3748/wjg.v23.i37.6920] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Revised: 07/30/2017] [Accepted: 08/15/2017] [Indexed: 02/06/2023] Open
Abstract
In their review, Arslan et al[1] did not describe the status of Helicobacter pylori (H. pylori) treatment with furazolidone and the resistance to this antibiotic. We have presented different surveys showing the resistance of H. pylori to furazolidone from Asia and South America. The resistance rates varied but were mostly low (< 5%). There are not enough data on its efficacy and resistance in the United States and Europe. H. pylori mutations occurring in the oorD gene, including A041G, A122G, C349A(G), A78G, A112G, A335G, C156T and C165T, and in the porD gene, including G353A, A356G, C357T, C347T, C347G and C346A, have been indicated to be possibly related to the observed resistance. Additionally, to complete Arslan et al's statement regarding levofloxacin resistance, it should be noted that compound mutations of N87A, A88N and V65I at codon Asn-87 were recently observed in the gyrA gene for the first time. However, the results on these topics are not sufficient, and more worldwide studies are suggested.
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Affiliation(s)
- Mohammad Zamani
- Student Research Committee, Babol University of Medical Sciences, Babol 47176-47745, Iran
- Cancer Research Center, Health Research Institute, Babol University of Medical Sciences, Babol 47176-47745, Iran
| | - Arash Rahbar
- Student Research Committee, Babol University of Medical Sciences, Babol 47176-47745, Iran
| | - Javad Shokri-Shirvani
- Department of Internal Medicine, Babol University of Medical Sciences, Babol 47176-47745, Iran
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18
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Shao Y, Lu R, Yang Y, Xu Q, Wang B, Ye G. Antibiotic resistance of Helicobacter pylori to 16 antibiotics in clinical patients. J Clin Lab Anal 2017; 32:e22339. [PMID: 28984385 DOI: 10.1002/jcla.22339] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Accepted: 09/19/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Resistance of Helicobacter pylori (H. pylori) to antibiotics is increasing worldwide. To determine the status of H. pylori resistance and its patterns in clinical patients, an investigation utilizing susceptibility testing for commonly used antibiotics was needed. METHODS Total of 2283 H. pylori strains were collected from 2013 to 2016. The resistance and its patterns of these strains were tested by agar dilution method. The resistance rate and minimal inhibition concentration (MIC) in different gender groups were also analyzed. RESULTS The overall resistance rates were as following: amoxicillin (1.58%), clarithromycin (22.73%), levofloxacin (24.75%), furazolidone (1.49%), doxycycline (9.20%), cefetamet (97.20%), ceftriaxone (49.60%), cefuroxime (25.20%), gentamicin (3.73%), azithromycin (85.60%), rifampicin (2.80%), metronidazole (92.53%), ornidazole (94.27%), tinidazole (87.20%), ciprofloxacin (43.20%), and moxifloxacin (38.53%). There were only 64.08% strains pan-susceptible to amoxicillin, clarithromycin, levofloxacin, and furazolidone, followed by mono resistance (23.17%), double resistance (11.13%), triple resistance (1.36%), and quadruple resistance (0.26%). Significant differences in the resistance rate and MIC were also observed in different gender groups. CONCLUSION Antibiotic resistance trends of H. pylori is increasing in clinical patients. With the increasing resistance, it is imperative to individualized therapy based on the results of drug susceptibility testing.
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Affiliation(s)
- Yongfu Shao
- Department of Gastroenterology, the Affiliated Hospital of Ningbo University School of Medicine, Ningbo, China
| | - Rongdan Lu
- Department of Gastroenterology, the Affiliated Hospital of Ningbo University School of Medicine, Ningbo, China.,Ningbo University School of Medicine, Ningbo, China
| | - Yunben Yang
- Ningbo University School of Medicine, Ningbo, China
| | - Qiancheng Xu
- Department of Gastroenterology, the Affiliated Hospital of Ningbo University School of Medicine, Ningbo, China.,Ningbo University School of Medicine, Ningbo, China
| | - Bojun Wang
- Department of Gastroenterology, the Affiliated Hospital of Ningbo University School of Medicine, Ningbo, China
| | - Guoliang Ye
- Department of Gastroenterology, the Affiliated Hospital of Ningbo University School of Medicine, Ningbo, China
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Huang CC, Tsai KW, Tsai TJ, Hsu PI. Update on the first-line treatment for Helicobacter pylori infection - a continuing challenge from an old enemy. Biomark Res 2017; 5:23. [PMID: 28702193 PMCID: PMC5505131 DOI: 10.1186/s40364-017-0103-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Accepted: 06/29/2017] [Indexed: 02/07/2023] Open
Abstract
Because the prevalence of antibiotic resistance markedly increases with time worldwide, anti-H. pylori treatment is continuing to be a great challenge forsphysicians in clinical practice. The Real-world Practice & Expectation of Asia-Pacific Physicians and Patients in Helicobacter Pylori Eradication (REAP-HP) Survey demonstrated that the accepted minimal eradication rate of anti-H. pylori regimen in H. pylori-infected patients was 91%. The Kyoto Consensus Report on Helicobacter Pylori Gastritis also recommended that, within any region, only regimens which reliably produce eradication rates of ≥90% in that population should be used for empirical treatment. This article is aimed to review current first-line eradication regimens with a per-protocol eradication rate exceeding 90% in most geographic areas. In regions with low (≦15%) clarithromycin resistance, 14-day hybrid (or reverse hybrid), 10 ~ 14-day sequential, 7 ~ 14-day concomitant, 10 ~ 14-day bismuth quadruple or 14-day triple therapy can achieve a high eradication rate in the first-line treatment of H. pylori infection. However, in areas with high (>15%) clarithromycin resistance, standard triple therapy should be abandoned because of low eradication efficacy, and 14-day hybrid (or reverse hybrid), 10 ~ 14-day concomitant or 10 ~ 14-day bismuth quadruple therapy are the recommended regimens. If no recent data of local antibiotic resistances of H. pylori strains are available, universal high efficacy regimens such as 14-day hybrid (or reverse hybrid), concomitant or bismuth quadruple therapy can be adopted to meet the recommendation of consensus report and patients' expectation.
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Affiliation(s)
- Chih-Chieh Huang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Kuo-Wang Tsai
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Tzung-Jiun Tsai
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
- Taiwan Acid-related Disease (TARD) Study Group, Kaohsiung, Taiwan
| | - Ping-I Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
- Taiwan Acid-related Disease (TARD) Study Group, Kaohsiung, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Kaoshiung Veterans General Hospital, 386 Ta Chung 1st Road, Kaohsiung, 813 Taiwan, ROC
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Sapmaz F, Kalkan IH, Atasoy P, Basyigit S, Guliter S. A Non-Inferiority Study: Modified Dual Therapy Consisting Higher Doses of Rabeprazole Is as Successful as Standard Quadruple Therapy in Eradication of Helicobacter pylori. Am J Ther 2017; 24:e393-e398. [DOI: 10.1097/mjt.0000000000000316] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Wang L, Lin Z, Chen S, Li J, Chen C, Huang Z, Ye B, Ding J, Li W, Wu L, Jiang Y, Meng L, Du Q, Si J. Ten-day bismuth-containing quadruple therapy is effective as first-line therapy for Helicobacter pylori –related chronic gastritis: a prospective randomized study in China. Clin Microbiol Infect 2017; 23:391-395. [DOI: 10.1016/j.cmi.2016.12.032] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2016] [Revised: 12/25/2016] [Accepted: 12/28/2016] [Indexed: 12/14/2022]
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22
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Li L, Ke Y, Yu C, Li G, Yang N, Zhang J, Li Y. Antibiotic resistance of Helicobacter pylori in Chinese children: A multicenter retrospective study over 7 years. Helicobacter 2017; 22. [PMID: 28098401 DOI: 10.1111/hel.12373] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND To determine the prevalence of resistance to metronidazole, clarithromycin, levofloxacin, amoxicillin, and furazolidone in Helicobacter pylori isolated from Chinese children. MATERIALS AND METHODS This multicenter retrospective study was conducted from January 2009 to December 2015. A total of 1746 isolates of H. pylori were collected from nine areas of Zhejiang province in the southeast coastal region of China. H. pylori strains were examined for antibiotics susceptibility by agar dilution method. RESULTS The resistance rates were 75.20% for metronidazole, 16.38% for clarithromycin, 6.70% for levofloxacin, 0.06% for amoxicillin, and 0.06% for furazolidone. The pattern of H. pylori antibiotic resistance demonstrated no significant changes in the rates of resistance to clarithromycin, amoxicillin, furazolidone, and metronidazole over 7 years. A significant trend of increasing resistance to metronidazole was observed as children aged, but a downward trend in clarithromycin resistance was observed as children aged. No difference in the resistance to other antibiotics was observed among different age groups. Also, there was no significant difference between male and female subjects in rates of resistance to these five types of antibiotics. The predominant dual resistance to metronidazole and clarithromycin was presented in 10.65% of the isolates. CONCLUSIONS The resistance rates of H. pylori in children from southeast coastal region of China were very high to metronidazole, moderate to clarithromycin and levofloxacin, and low to amoxicillin and furazolidone. It is important to continue monitoring the resistance profiles of H. pylori isolated in this region.
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Affiliation(s)
- Lan Li
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yini Ke
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Guogang Li
- Department of Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Ningmin Yang
- Zhiyuan Medical Inspection Institute Co., Ltd., Hangzhou, China
| | - Jianzhong Zhang
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing, China
- National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Youming Li
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Optimal First-Line Treatment for Helicobacter pylori Infection: Recent Strategies. Gastroenterol Res Pract 2016; 2016:9086581. [PMID: 28070184 PMCID: PMC5187483 DOI: 10.1155/2016/9086581] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Revised: 10/15/2016] [Accepted: 11/03/2016] [Indexed: 01/06/2023] Open
Abstract
A new treatment strategy is needed, as the efficacy of triple therapy containing clarithromycin—the current standard treatment for Helicobacter pylori infection—is declining. Increasing antibiotic resistance of H. pylori is the most significant factor contributing to eradication failure. Thus, selecting the most appropriate regimen depending on resistance is optimal, but identifying resistance to specific antibiotics is clinically challenging. In a region suspected to have high clarithromycin resistance, bismuth quadruple therapy and so-called nonbismuth quadruple therapies (sequential, concomitant, and sequential-concomitant hybrid) are some first-line regimen options. However, more research is needed regarding appropriate second-line treatments after first-line treatment failure. Tailored therapy, which is based on antibiotic sensitivity testing, would be optimal but has several limitations for clinical use, and an alternative technique is required. A novel potassium-competitive acid blocker-based eradication regimen could be a valuable eradication option in the near future.
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Cao Z, Chen Q, Zhang W, Liang X, Liao J, Liu W, Xiao S, Lu H. Fourteen-day optimized levofloxacin-based therapy versus classical quadruple therapy for Helicobacter pylori treatment failures: a randomized clinical trial. Scand J Gastroenterol 2016; 50:1185-90. [PMID: 25881966 DOI: 10.3109/00365521.2015.1037345] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To test the efficacy of lansoprazole, bismuth, levofloxacin, and amoxicillin therapy compared to bismuth metronidazole tetracycline (BMT) quadruple therapy for second-line treatment of Helicobacter pylori infection. METHODS A total of 284 patients who failed prior H. pylori eradication were randomized to receive 14-day regimens containing lansoprazole 30 mg twice a day (b.i.d.), bismuth subcitrate 240 mg b.i.d., and either amoxcillin, 1 g b.i.d. and levofloxacin 500 mg once daily (qd) (levofloxacin/bismuth therapy) or metronidazole 400 mg four times daily (q.i.d.) and tetracycline, 500 mg q.i.d. (BMT quadruple therapy). Endoscopy and culture were performed before treatment. Antimicrobial susceptibility was by agar dilution. H. pylori status was determined 6 weeks after the end of therapy using a (13)C-urea breath test. RESULTS The metronidazole, levofloxacin, tetracycline, and amoxicillin resistance rates were 85.3%, 40.2%, 1.1%, and 0.5%, respectively. The intention-to-treat and per-protocol (PP) eradication rates were 83% (95% confidence interval [CI]: 75.9-88.3%) and 88.1% (95% CI: 81.2-92.4%) (p = 0.22) for levofloxacin-bismuth (levo-bismuth) versus BMT quadruple, respectively, and PP rates were 85.4% (95% CI: 78.5-90.3%) and 90.6% (95% CI: 84.6-94.5%) (p = 0.18). Moderate and severe side effects were significantly higher with BMT quadruple than levo-bismuth (22.4% vs. 5%, p < 0.001) and higher in women (28.4%) than men (10.4%) in BMT quadruple therapy group (p = 0.015). CONCLUSION Increasing fluoroquinolone resistance has undermined levo-bismuth quadruple therapy making BMT quadruple therapy a better choice empiric second-line therapy for H. pylori infection. However, compliance was significantly higher with levo-bismuth quadruple therapy, especially among women.
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Affiliation(s)
- Zhijun Cao
- Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease , Shanghai , China
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Dore MP, Lu H, Graham DY. Role of bismuth in improving Helicobacter pylori eradication with triple therapy. Gut 2016; 65:870-8. [PMID: 26848181 DOI: 10.1136/gutjnl-2015-311019] [Citation(s) in RCA: 207] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2015] [Accepted: 01/05/2016] [Indexed: 12/13/2022]
Abstract
In most regions of the world, antimicrobial resistance has increased to the point where empirical standard triple therapy for Helicobacter pylorieradication is no longer recommended. The treatment outcome in a population is calculated as the sum of the treatment success in the subpopulation with susceptible infections plus treatment success in the subpopulation with resistant infections. The addition of bismuth (i.e., 14-day triple therapy plus bismuth) can improve cure rates despite a high prevalence of antimicrobial resistance. The major bismuth effect is to add an additional 30%-40% to the success with resistant infections. The overall result is therefore dependent on the prevalence of resistance and the treatment success in the subpopulation with resistant infections (eg, with proton-pump inhibitor-amoxicillin dual therapy). Here, we explore the contribution of each component and the mechanisms of how bismuth might enhance the effectiveness of triple therapy. We also discuss the limitations of this approach and provide suggestions how triple therapy plus bismuth might be further improved.
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Affiliation(s)
- Maria Pina Dore
- Dipartimento di Medicina Clinica e Sperimentale, Clinica Medica, University of Sassari, Sassari, Italy Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Hong Lu
- GI Division, Ren Ji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, China Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - David Y Graham
- Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
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Hu B, Zhao F, Wang S, Olszewski MA, Bian H, Wu Y, Kong M, Xu L, Miao Y, Fang Y, Yang C, Zhao H, Zhang Y. A high-throughput multiplex genetic detection system for Helicobacter pylori identification, virulence and resistance analysis. Future Microbiol 2016; 11:1261-1278. [PMID: 27023051 DOI: 10.2217/fmb-2016-0023] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM We established a high-throughput multiplex genetic detection system (HMGS) for identification of Helicobacter pylori with concomitant analysis of virulence and drug resistance. MATERIALS & METHODS Confirmed 132 H. pylori cultures from gastric biopsies were screened by 20-gene site-HMGS, sequencing and E-test. RESULTS HMGS was highly sensitive and specific for H. pylori identification. Concordance rate between HMGS and sequencing averaged 94.5% (virulence genes) and 97.3% (resistance genes). Observed resistance rates to four mainstream antibiotics were high, except for amoxicillin. Significant association between virulence genotype and risks for specific gastrointestinal diseases was found for five genes. Metronidazole resistance in peptic ulcer patients was significantly higher. CONCLUSION HMGS is an effective method for H. pylori identification and analysis of virulence and drug resistance.
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Affiliation(s)
- Binjie Hu
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, No. 221 Yanan West Road, Shanghai, 200040, China
| | - Fuju Zhao
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, No. 221 Yanan West Road, Shanghai, 200040, China
| | - Shiwen Wang
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, No. 221 Yanan West Road, Shanghai, 200040, China
| | - Michal A Olszewski
- Division of Pulmonary & Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System & Research Service, VA Ann Arbor Health Systems, Ann Arbor, MI, USA
| | - Haipeng Bian
- Department of Gastroenterology, Tongji Hospital Affiliated to Shanghai Tongji University, Shanghai, China
| | - Yong Wu
- Ningbo HEALTH Gene Technologies Co., Ltd., Ningbo, China
| | - Mimi Kong
- Ningbo HEALTH Gene Technologies Co., Ltd., Ningbo, China
| | - Lingli Xu
- Shanghai ABSciex Analytical Instrument Trading Co., Ltd., Shanghai, China
| | - Yingxin Miao
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, No. 221 Yanan West Road, Shanghai, 200040, China
| | - Yi Fang
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, No. 221 Yanan West Road, Shanghai, 200040, China
| | - Changqing Yang
- Department of Gastroenterology, Tongji Hospital Affiliated to Shanghai Tongji University, Shanghai, China
| | - Hu Zhao
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, No. 221 Yanan West Road, Shanghai, 200040, China.,Key Laboratory of Clinical Geriatric Medicine, Shanghai, China.,Research Center on Aging & Medicine, Fudan University, Shanghai, China
| | - Yanmei Zhang
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, No. 221 Yanan West Road, Shanghai, 200040, China.,Key Laboratory of Clinical Geriatric Medicine, Shanghai, China.,Research Center on Aging & Medicine, Fudan University, Shanghai, China
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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: 540] [Impact Index Per Article: 60.0] [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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Dong F, Ji D, Huang R, Zhang F, Huang Y, Xiang P, Kong M, Nan L, Zeng X, Wu Y, Bao Z. Multiple Genetic Analysis System-Based Antibiotic Susceptibility Testing in Helicobacter pylori and High Eradication Rate With Phenotypic Resistance-Guided Quadruple Therapy. Medicine (Baltimore) 2015; 94:e2056. [PMID: 26632710 PMCID: PMC5058979 DOI: 10.1097/md.0000000000002056] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Antibiotics resistance in Helicobacter pylori (H. pylori) is the major factor for eradication failure. Molecular tests including fluorescence in situ hybridization, PCR-restriction fragment length polymorphism, and dual priming oligonucleotide-PCR (DPO-PCR) play critical roles in the detection of antibiotic susceptibility; however, limited knowledge is known about application of multiple genetic analysis system (MGAS) in the area of H. pylori identification and antibiotics resistance detection.The aim of this study is to determine the antibiotics resistance using different molecular tests and evaluate the treatment outcomes of E-test-based genotypic resistance.A total of 297 patients with dyspepsia complaint were recruited for gastroscopies. Ninety patients with H. pylori culture positive were randomly divided into 2 groups (test group and control group). E-test, general PCR, and MGAS assay were performed in test group. Patients in control group were treated with empirical therapy (rabeprazole + bismuth potassium citrate + amoxicillin [AMX] + clarithromycin [CLR]), whereas patients in test group received quadruple therapy based on E-test results twice daily for 14 consecutive days. The eradication effect of H. pylori was confirmed by C-urea breath test after at least 4 weeks when treatment was finished.Rapid urease test showed 46.5% (128/297) patients with H. pylori infection, whereas 30.3% (90/297) patients were H. pylori culture positive. E-test showed that H. pylori primary resistance rate to CLR, AMX, metronidazole, tetracycline, and levofloxacin (LVX) was 40.0% (18/45), 4.4% (2/45), 53.3% (24/45), 0% (0/45), and 55.6% (25/45), respectively. In addition, there are many multidrug resistant (MDR) phenotypes, and the MDR strains have higher minimum inhibitory concentration than their single-drug resistant counterparts. Considering E-test as the reference test, the sensitivities of general PCR and MGAS in detecting CLR resistance were 83.3% (15/18) and 94.4% (17/18), whereas in detecting LVX resistance were 100% (25/25) and 83.3% (15/18), respectively. Finally, the eradication rate in test group was significantly higher than that in control group as demonstrated by intention-to-treat analysis and per-protocol analysis.MGAS is a promising assay for H. pylori identification and antibiotic susceptibility testing. Phenotypic resistance-guided quadruple therapy showed a high efficacy in treating patients with H. pylori infection.
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Affiliation(s)
- Fangyuan Dong
- From the Department of Gastroenterology (FD, FZ, YH, ZB), Shanghai Key Laboratory of Clinical Geriatric Medicine; Department of Digestive Endoscopy Center (DJ, RH, PX), Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai, PR China; and Ningbo HEALTH Gene Technologies Co., Ltd. (MK, LN, XZ, YW), Ningbo, PR China
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Zhang W, Chen Q, Liang X, Liu W, Xiao S, Graham DY, Lu H. Bismuth, lansoprazole, amoxicillin and metronidazole or clarithromycin as first-line Helicobacter pylori therapy. Gut 2015; 64:1715-20. [PMID: 26338726 DOI: 10.1136/gutjnl-2015-309900] [Citation(s) in RCA: 116] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Accepted: 08/11/2015] [Indexed: 01/06/2023]
Abstract
OBJECTIVE To evaluate the efficacy and tolerability of replacing tetracycline with amoxicillin in bismuth quadruple therapy. DESIGN Subjects who were infected with Helicobacter pylori and naïve to treatment were randomly (1:1) assigned to receive a 14-day modified bismuth quadruple therapy: lansoprazole 30 mg, amoxicillin 1 g, bismuth potassium citrate 220 mg (elemental bismuth), twice a day with metronidazole 400 mg four times a day (metronidazole group) or clarithromycin 500 mg twice a day (clarithromycin group). Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. This was a non-inferiority trial. RESULTS Two hundred and fifteen subjects were randomised. Metronidazole and clarithromycin containing regimens achieved high cure rates: 94 of 97 (96.9%, 95% CI 93.5% to 100%) and 93 of 98 (94.9%, 95% CI 90.5% to 99.3%) by per-protocol and 88.9% (95% CI 83.0% to 94.8%) and 88.8% (95% CI 82.8% to 94.8%) by intention-to-treat, respectively. Amoxicillin, metronidazole and clarithromycin resistance rates were 1.5%, 45.5% and 26.5%, respectively. Only clarithromycin resistance reduced treatment success (e.g., susceptible 98.6%, resistant 76.9%, p=0.001). Adverse events were more common in the metronidazole group. CONCLUSIONS These results suggest that amoxicillin can substitute for tetracycline in modified 14 day bismuth quadruple therapy as first-line treatment and still overcome metronidazole resistance in areas with high prevalence of metronidazole and clarithromycin resistance. Using clarithromycin instead of metronidazole was only effective in the presence of susceptible strains. TRIAL REGISTRATION NUMBER NCT02175901.
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Affiliation(s)
- Wei Zhang
- GI Division, Renji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Institution of Digestive Disease, Shanghai, China Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - Qi Chen
- GI Division, Renji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Institution of Digestive Disease, Shanghai, China Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - Xiao Liang
- GI Division, Renji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Institution of Digestive Disease, Shanghai, China Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - Wenzhong Liu
- GI Division, Renji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Institution of Digestive Disease, Shanghai, China Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - Shudong Xiao
- GI Division, Renji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Institution of Digestive Disease, Shanghai, China Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - David Y Graham
- Michael E. DeBakey VA Medical Center, and Baylor College of Medicine Houston, Houston, Texas, USA
| | - Hong Lu
- GI Division, Renji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Institution of Digestive Disease, Shanghai, China Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
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Li S, Lu XP, Ding BJ, Wang ZY. Efficacy and safety of doxycycline and furazolidone-based quadruple therapy as first-line treatment for Helicobacter pylori infection. Shijie Huaren Xiaohua Zazhi 2015; 23:4279-4283. [DOI: 10.11569/wcjd.v23.i26.4279] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the efficacy and safety of doxycycline and furazolidone-based quadruple therapy as first-line treatment for Helicobacter pylori (H. pylori) infection.
METHODS: 129 patients with H. pylori positive were randomly divided into two groups: therapy group and control group. Therapy group was treated with rabeprazole, doxycycline, furazolidone and bismuth potassium citrate, control group was treated with rabeprazole, amoxicillin, levofloxacin and bismuth potassium citrate. The rate of H. pylori eradication, the incidence of adverse reactions and cost-effectiveness ratio were compared between the two groups.
RESULTS: The rate of H. pylori eradication in therapy group was significantly higher than that in control group [per-protoc (PP): 91.7% vs 76.7%, P < 0.05; intent-to-treat (ITT): 85.9% vs 70.8%, P < 0.05]. The incidence of adverse reactions was no significant difference between therapy group and control group (14.5% vs 17.5%, P > 0.05). The cost-effectiveness analysis showed that the cost and the C/E value of the treatment group were lower than that in the control group.
CONCLUSION: Doxycycline and furazolidone-based quadruple therapy is associated with a high rate of H. pylori eradication and few slight side effects and can reduce the costs of quadruple treatment.
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Liou JM, Chang CY, Chen MJ, Chen CC, Fang YJ, Lee JY, Wu JY, Luo JC, Liou TC, Chang WH, Tseng CH, Wu CY, Yang TH, Chang CC, Wang H, Sheu BS, Lin JT, Bair MJ, Wu MS, Taiwan Gastrointestinal Disease and Helicobacter Consortium. The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy to Restrict Antibiotic Consumption and Its Relation to Virulence Factors-A Nationwide Study. PLoS One 2015; 10:e0124199. [PMID: 25942450 PMCID: PMC4420283 DOI: 10.1371/journal.pone.0124199] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Accepted: 02/26/2015] [Indexed: 02/06/2023] Open
Abstract
Objective The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance. Methods The defined daily dose (DDD) of antibiotics was analyzed using the Taiwan National Health Insurance (NHI) research database. H. pylori strains isolated from treatment naïve (N=1395) and failure from prior eradication therapies (N=360) from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method. Results The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000–2007 to 8.3% in 2008–2010 and 13.4% in 2011–2012 (p=0.001). The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001), which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance. Conclusions The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance.
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Affiliation(s)
- Jyh-Ming Liou
- Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chi-Yang Chang
- Department of Internal Medicine, E- DA Hospital and I-Shou University, Kaohsiung County, Taiwan
| | - Mei-Jyh Chen
- Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chieh-Chang Chen
- Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yu-Jen Fang
- Departments of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, National Taiwan University College of Medicine, Yun-Lin, Taiwan
| | - Ji-Yuh Lee
- Departments of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, National Taiwan University College of Medicine, Yun-Lin, Taiwan
| | - Jeng-Yih Wu
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jiing-Chyuan Luo
- Department of Medicine, National Yang-Ming University, School of Medicine, and Taipei Veterans General Hospital, Taipei, Taiwan
| | - Tai-Cherng Liou
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Wen-Hsiung Chang
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Cheng-Hao Tseng
- Department of Internal Medicine, E- DA Hospital and I-Shou University, Kaohsiung County, Taiwan
| | - Chun-Ying Wu
- Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan, and Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Tsung-Hua Yang
- Departments of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, National Taiwan University College of Medicine, Yun-Lin, Taiwan
| | - Chun-Chao Chang
- Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Hsiu‐Po Wang
- Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Bor-Shyang Sheu
- Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Jaw-Town Lin
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan, and Department of Nursing, Meiho University, Pingtung, Taiwan
- * E-mail: (MSW); (MJB)
| | - Ming-Shiang Wu
- Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
- * E-mail: (MSW); (MJB)
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Cao Q, Didelot X, Wu Z, Li Z, He L, Li Y, Ni M, You Y, Lin X, Li Z, Gong Y, Zheng M, Zhang M, Liu J, Wang W, Bo X, Falush D, Wang S, Zhang J. Progressive genomic convergence of two Helicobacter pylori strains during mixed infection of a patient with chronic gastritis. Gut 2015; 64:554-61. [PMID: 25007814 PMCID: PMC4392222 DOI: 10.1136/gutjnl-2014-307345] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To study the detailed nature of genomic microevolution during mixed infection with multiple Helicobacter pylori strains in an individual. DESIGN We sampled 18 isolates from a single biopsy from a patient with chronic gastritis and nephritis. Whole-genome sequencing was applied to these isolates, and statistical genetic tools were used to investigate their evolutionary history. RESULTS The genomes fall into two clades, reflecting colonisation of the stomach by two distinct strains, and these lineages have accumulated diversity during an estimated 2.8 and 4.2 years of evolution. We detected about 150 clear recombination events between the two clades. Recombination between the lineages is a continuous ongoing process and was detected on both clades, but the effect of recombination in one clade was nearly an order of magnitude higher than in the other. Imputed ancestral sequences also showed evidence of recombination between the two strains prior to their diversification, and we estimate that they have both been infecting the same host for at least 12 years. Recombination tracts between the lineages were, on average, 895 bp in length, and showed evidence for the interspersion of recipient sequences that has been observed in in vitro experiments. The complex evolutionary history of a phage-related protein provided evidence for frequent reinfection of both clades by a single phage lineage during the past 4 years. CONCLUSIONS Whole genome sequencing can be used to make detailed conclusions about the mechanisms of genetic change of H. pylori based on sampling bacteria from a single gastric biopsy.
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Affiliation(s)
- Qizhi Cao
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China,Department of Immunology, Binzhou Medical University, Yantai, China
| | - Xavier Didelot
- Department of Infectious Disease Epidemiology, Imperial College London, London, UK
| | - Zhongbiao Wu
- The First People's Hospital of Wenling, the Affiliated Wenling Hospital of Wenzhou Medical College, Zhejiang, China
| | - Zongwei Li
- Beijing Institute of Radiation Medicine, Beijing, China
| | - Lihua He
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
| | - Yunsheng Li
- The First People's Hospital of Wenling, the Affiliated Wenling Hospital of Wenzhou Medical College, Zhejiang, China
| | - Ming Ni
- Beijing Institute of Radiation Medicine, Beijing, China
| | - Yuanhai You
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
| | - Xi Lin
- The First People's Hospital of Wenling, the Affiliated Wenling Hospital of Wenzhou Medical College, Zhejiang, China
| | - Zhen Li
- Beijing Institute of Radiation Medicine, Beijing, China
| | - Yanan Gong
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
| | - Minqiao Zheng
- The First People's Hospital of Wenling, the Affiliated Wenling Hospital of Wenzhou Medical College, Zhejiang, China
| | - Minli Zhang
- Beijing Institute of Radiation Medicine, Beijing, China
| | - Jie Liu
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
| | - Weijun Wang
- The First People's Hospital of Wenling, the Affiliated Wenling Hospital of Wenzhou Medical College, Zhejiang, China
| | - Xiaochen Bo
- Beijing Institute of Radiation Medicine, Beijing, China
| | - Daniel Falush
- Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany,Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan
| | - Shengqi Wang
- Beijing Institute of Radiation Medicine, Beijing, China
| | - Jianzhong Zhang
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
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Abstract
Helicobacter pylori (H. pylori) infection has been associated with gastric disorders. The situation of H. pylori infection in China-where a high prevalence of H. pylori infection, a high incidence of gastric cancer, and widespread resistance to clarithromycin, metronidazole, and levofloxacin exist-is quite different from that in Western countries. In order for Chinese clinicians to better manage H. pylori infection, a Chinese Study Group on H. pylori published four consensus reports regarding the management of H. pylori infection in China between 1999 and 2012. The eradication rate with standard triple therapy was <80% in most areas of China. Bismuth is available in China, and bismuth-containing quadruple therapy has been shown to produce a high eradication rate; thus, bismuth quadruple therapy could be recommended both as an initial and as a rescue therapy in China. There is no advantage of sequential therapy over triple therapy in Chinese patients, but the efficacy of concomitant therapy must be studied further. This review introduces the epidemiology, diagnosis, indicators, and therapies for the eradication of H. pylori in China in recent years.
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Affiliation(s)
- Chuan Xie
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China
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Ren L, Lu H, Li HY, Zhu LY, Xu XQ, Gu LY, Ge ZZ, Li XB. New dual therapy for primary treatment of Helicobacter pylori infection: A prospective randomized study in Shanghai, China. J Dig Dis 2014; 15:622-7. [PMID: 25205201 DOI: 10.1111/1751-2980.12186] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To evaluate the eradication rates, side effects and the patient compliance of a dual therapy with rabeprazole and amoxicillin as the first-line therapy in patients with Helicobacter pylori (H. pylori) infection. METHODS A total of 120 patients diagnosed endoscopically with non-ulcer dyspepsia with H. pylori infection were randomly assigned into two groups, one treated with amoxicillin 1 g thrice daily plus rabeprazole 10 mg twice daily (R10A group) or 20 mg twice daily (R20A group) for 14 days. H. pylori eradication was evaluated by (13) C-urea breath test (UBT) at 4-6 weeks after the completion of treatment. H. pylori eradication rate was analyzed by per-protocol (PP) and intention-to-treat (ITT) analyses together with 95% confidence interval (CI). Side effects and patients' compliance were also recorded. RESULTS Overall, 117 patients (58 in the R10A group and 59 in the R20A group) completed the study, among whom five did not undertake the UBT. H. pylori eradication was achieved in 89.8% of patients in the R20A group by ITT analysis and 93.0% by PP analysis, which was significantly higher than those in the R10A group (75.9% and 80.0%, respectively, P < 0.05). Side effects, including skin rash, abdominal discomfort, headache, insomnia and nausea, were all mild and were treated symptomatically without the need to discontinue the treatment. CONCLUSION The modified dual therapy with high doses of rabeprazole and amoxicillin is considered an effective and safe primary therapy for H. pylori eradication and could be recommended as the first-line eradication regimen for certain patients.
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Affiliation(s)
- Ling Ren
- State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China
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Zhang Y, Gao W, Cheng H, Zhang X, Hu F. Tetracycline- and furazolidone-containing quadruple regimen as rescue treatment for Helicobacter pylori infection: a single center retrospective study. Helicobacter 2014; 19:382-386. [PMID: 24849129 DOI: 10.1111/hel.12143] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND OBJECTIVE Eradication rate of Helicobacter pylori decreases worldwide, while antibiotics resistance rates of H. pylori increase rapidly in recent years. In most cases, H. pylori would be resistant to clarithromycin, metronidazole, and quinolone if these antibiotics had been used as component of eradication regimen. H. pylori strains resistant to both tetracycline and furazolidone are rare. The aim of our study was to evaluate efficacy and side effects of tetracycline- and furazolidone-containing quadruple regimen as rescue treatment. METHODS Patients with H. pylori infection given RTFB (rabeprazole 20 mg b.i.d. + tetracycline 750 mg b.i.d. +furazolidone 100 mg b.i.d. + colloidal bismuth subcitrate 200 mg b.i.d.) regimen for 14 days as rescue treatment were enrolled in this retrospective study. Eradication status was evaluated by (13) C-urea breath test, and side effects were collected. RESULTS One hundred and nine patients were enrolled. The intention-to-treat eradication rate was 91.74% (100 of 109) and 95.24% (100 of 105) per protocol analysis. Side effects including fever, palpitation, and skin rash occurred in 35 patients. CONCLUSIONS The 14-day tetracycline- and furazolidone-containing quadruple regimen can achieve a relatively high eradication rate as rescue treatment. Some side effects including fever may occur during the treatment.
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Affiliation(s)
- Yuemiao Zhang
- Department of Integrated TCM & Western Medicine, Peking University First Hospital, Beijing, China
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36
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Xie Y, Zhu Y, Zhou H, Lu ZF, Yang Z, Shu X, Guo XB, Fan HZ, Tang JH, Zeng XP, Wen JB, Li XQ, He XX, Ma JH, Liu DS, Huang CB, Xu NJ, Wang NR, Lu NH. Furazolidone-based triple and quadruple eradication therapy for Helicobacter pylori infection. World J Gastroenterol 2014; 20:11415-11421. [PMID: 25170230 PMCID: PMC4145784 DOI: 10.3748/wjg.v20.i32.11415] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2013] [Revised: 03/19/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the efficacy of furazolidone-based triple and quadruple therapy in eradicating Helicobacter pylori (H. pylori) in a multi-center randomized controlled trial.
METHODS: A total of 720 H. pylori positive patients with duodenal ulcer disease were enrolled at 10 different hospitals in Jiangxi province in China. The patients were randomly assigned to four treatment groups as follows: patients in Groups 1 and 3 received rabeprazole (10 mg), amoxicillin (1000 mg) and furazolidone (100 mg) twice daily for 7 and 10 d, respectively; patients in Groups 2 and 4 received rabeprazole (10 mg), bismuth (220 mg), amoxicillin (1000 mg) and furazolidone (100 mg) twice daily for 7 and 10 d, respectively. The primary outcome measure was H. pylori eradication rate 4 wk after treatment by intention-to-treat and per protocol analysis, while the secondary outcome measures were symptom and sign changes at the end of treatment and 4 wk after the end of treatment, as well as the proportion of patients who developed adverse events.
RESULTS: The demographic data of the four groups were not significantly different. Overall, 666 patients completed the scheme and were re-assessed with the 13C-urea breath test. The intention-to-treat analysis of the H. pylori eradication rates in Groups 1, 2, 3 and 4 were 74.44%, 82.78%, 78.89% and 86.11%, respectively. The H. pylori eradication rate in Group 4 was significantly higher than that in Group 1. According to the per protocol analysis, the H. pylori eradication rates in Groups 1, 2, 3 and 4 were 81.21%, 89.22%, 85.54% and 92.26%, respectively. The H. pylori eradication rate in Group 4 was significantly higher than that in Group 1. The number of adverse events was 15 (8.3%), 16 (8.9%), 15 (8.3%) and 17 (9.4%) in Groups 1, 2, 3 and 4, respectively, including dizziness, vomiting, diarrhea, nausea, skin rash, itchy skin, and malaise. The symptoms were relieved without special treatment in all of the patients.
CONCLUSION: Both 7- and 10-d quadruple furazolidone-based therapies achieve satisfactory H. pylori eradication rates.
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Alfizah H, Norazah A, Hamizah R, Ramelah M. Resistotype of Helicobacter pylori isolates: the impact on eradication outcome. J Med Microbiol 2014; 63:703-709. [PMID: 24757218 DOI: 10.1099/jmm.0.069781-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Antibiotic resistance is increasing worldwide, and it has been regarded as the main factor reducing the efficacy of Helicobacter pylori therapy. The aim of this study was to determine the phenotype and genotype of antibiotic-resistant strains of H. pylori in the Malaysian population and to evaluate the impact of antibiotic resistance to eradication outcome. One hundred and sixty-one H. pylori isolates were analysed in this study. Metronidazole, clarithromycin, fluoroquinolone, amoxicillin and tetracycline susceptibilities were determined by Etest. PCR followed by DNA sequencing was carried out to determine mutations. The medical records of the patients infected with resistant strains were reviewed to determine the eradication outcome. Metronidazole resistance was encountered in 36.6 % of H. pylori isolates, whereas clarithromycin and fluoroquinolone resistance was observed in 1.2 and 1.9 % of isolates, respectively. All strains tested were susceptible to amoxicillin and tetracycline. Frameshift and nonsense mutations in rdxA and frxA genes resulting in stop codons contributed to metronidazole resistance, which leads to reduced eradication efficacy. A2142G and A2143G mutations of 23S rRNA were identified as causing failure of the eradication therapy. Mutation at either codon 87 or 91 of the gyrA gene was identified in fluoroquinolone-resistant strains. However, the effect of resistance could not be assessed. This study showed that frameshift and nonsense mutations in rdxA or frxA genes and point mutations in the 23S rRNA affected the efficacy of H. pylori eradication therapy.
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Affiliation(s)
- Hanafiah Alfizah
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Malaysia
| | - Ahmad Norazah
- Bacteriology Unit, Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Malaysia
| | - Razlan Hamizah
- Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Malaysia
| | - Mohamed Ramelah
- Centre for Innovative Collaboration, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia
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Wu JY, Wang SSW, Lee YC, Yamaoka Y, Graham DY, Jan CM, Wang WM, Wu DC. Detection of genotypic clarithromycin-resistant Helicobacter pylori by string tests. World J Gastroenterol 2014; 20:3343-9. [PMID: 24695835 PMCID: PMC3964405 DOI: 10.3748/wjg.v20.i12.3343] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2013] [Revised: 09/17/2013] [Accepted: 10/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the utility of the string test to detect genotypic clarithromycin-resistant Helicobacter pylori (H. pylori) by polymerase chain reaction (PCR)-restriction fragment length polymorphism. METHODS Patients undergoing endoscopic examinations were enrolled in the present study. String tests were done on the next day of endoscopy. Segments of 23S rRNA were amplified from DNA obtained from string tests. PCR-restriction fragment length polymorphism was accomplished by restriction enzymes BbsI and BsaI recognizing the mutation site A to G at 2143 or at 2142 of 23S rRNA domain V, respectively. RESULTS One hundred and thirty-four patients with H. pylori infection underwent string tests. To compare phenotypic resistance, 43 isolates were successfully cultured in 79 patients in whom 23S rRNA was successfully amplified. Of five patients with clarithromycin-resistant H. pylori, 23S rRNA of H. pylori isolates from four patients could be digested by BsaI. In 38 susceptible isolates, 23S rRNA of H. pylori isolates from 36 patients could not be digested by either BsaI or BbsI. The sensitivity and specificity of the string test to detect genotypic clarithromycin resistance were 66.7% and 97.3%, respectively. Positive and negative predictive values were 80% and 94.7%, respectively. CONCLUSION String test with molecular analysis is a less invasive method to detect genotypic resistance before treatment. Further large-scale investigations are necessary to confirm our results.
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Lee SY. Current progress toward eradicating Helicobacter pylori in East Asian countries: Differences in the 2013 revised guidelines between China, Japan, and South Korea. World J Gastroenterol 2014; 20:1493-1502. [PMID: 24587624 PMCID: PMC3925857 DOI: 10.3748/wjg.v20.i6.1493] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2013] [Revised: 10/02/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
New 2013 guidelines on Helicobacter pylori (H. pylori) infection have been published in China, Japan, and South Korea. Like the previous ones, these new guidelines differ between the three countries with regard to the indications for H. pylori eradication, diagnostic methods, and treatment regimens. The most profound change among all of the guidelines is that the Japanese national health insurance system now covers the expenses for all infected subjects up to second-line treatment. This makes the Japanese indications for eradication much wider than those in China and South Korea. With regard to the diagnosis, a serum H. pylori antibody test is not recommended in China, whereas it is considered to be the most reliable method in Japan. A decrease relative to the initial antibody titer of more than 50% after 6-12 mo is considered to be the most accurate method for determining successful eradication in Japan. In contrast, only the urea breath test is recommended after eradication in China, while either noninvasive or invasive methods (except the bacterial culture) are recommended in South Korea. Due to the increased rate of antibiotics resistance, first-line treatment is omitted in China and South Korea in cases of clarithromycin resistance. Notably, the Japanese regimen consists of a lower dose of antibiotics for a shorter duration (7 d) than in the other countries. There is neither 14 d nor bismuth-based regimen in the first-line and second-line treatment in Japan. Such differences among countries might be due to differences in the approvals granted by the governments and national health insurance system in each country. Further studies are required to achieve the best results in the diagnosis and treatment of H. pylori infection based on cost-effectiveness in East Asian countries.
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Huang J, Zhou L, Geng L, Yang M, Xu XW, Ding ZL, Mao M, Wang ZL, Li ZL, Li DY, Gong ST. Randomised controlled trial: sequential vs. standard triple therapy for Helicobacter pylori infection in Chinese children-a multicentre, open-labelled study. Aliment Pharmacol Ther 2013; 38:1230-5. [PMID: 24117692 DOI: 10.1111/apt.12516] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2013] [Revised: 05/01/2013] [Accepted: 09/12/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Studies have showed that 10-day sequential treatment regimen achieved higher Helicobacter pylori eradication rate than standard triple therapies. AIM To compare a 10-day sequential therapy and standard triple therapy in Chinese children with H. pylori infection. METHODS A prospective, multicentre, open-label, randomised controlled trial was conducted in four tertiary medical centres in China. Children with H. pylori gastritis were randomly assigned to a 10-day sequential therapy consisting of omeprazole and amoxicillin for 5 days followed by omeprazole, clarithromycin and metronidazole for the remaining 5 days, or 7-day or 10-day standard triple therapy comprising of omeprazole, amoxicillin and clarithromycin. H. pylori eradication was assessed by H. pylori stool antigen test. RESULTS A total of 360 patients were included. The eradication rate achieved with the 10-day sequential therapy was significantly higher than either the 7-day or 10-day standard triple treatment, either by the intention-to-treat analysis (81.4% vs. 61.9% or 67.7%, P < 0.05) or per-protocol analysis (89.7% vs. 70.8% or 77.8%, P < 0.05). CONCLUSIONS The 10-day sequential regimen was significantly more effective than standard 7-day or 10-day triple regimens in eradicating H. pylori infection in Chinese children.
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Affiliation(s)
- J Huang
- Guangzhou Women and Children's Medical Center of Guangzhou Medical College, Guangzhou, China
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Abstract
Antimicrobial resistance has continued to undermine many popular anti-Helicobacter pylori therapies. Antibiotic resistance to commonly used anti-H. pylori drugs in China has increased markedly, making China an ideal site to identify regimens that remain effective despite widespread antimicrobial resistance. Bismuth is one of the few antimicrobials to which resistance does not develop. Factors contributing to H. pylori treatment success include host factors (e.g., genetic differences in the metabolism of the drugs used), bacterial factors (e.g., susceptibility), and details of the regimen (e.g., doses, dosing interval, dosing in relation to meals, formulation, etc.). We reviewed the recent experience in China with bismuth-containing quadruple therapies. The experience consists of 16 studies with 25 arms involving 1971 patients to identify successful regimens (defined as reliably obtaining 90% or greater eradication per protocol) deserving further study. Despite high rates of resistance to commonly used antimicrobials, several regimens could achieve high success. These were characteristically 14-day regimens containing a proton pump inhibitor and either tetracycline and metronidazole or furazolidone and amoxicillin. We propose approaches for further development including for optimization and simplification related to convenience and side effects (e.g., twice rather than three or four times daily or administration at the noon and evening meal instead of at breakfast and evening) while maintaining effectiveness of at least 90%. Studies in China identified regimens that were highly effective despite the high prevalence of resistance to metronidazole, fluoroquinolones, and macrolides. Multicenter randomized studies will be required to confirm which is the best.
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Liao J, Zheng Q, Liang X, Zhang W, Sun Q, Liu W, Xiao S, Graham DY, Lu H. Effect of fluoroquinolone resistance on 14-day levofloxacin triple and triple plus bismuth quadruple therapy. Helicobacter 2013; 18:373-7. [PMID: 23581720 PMCID: PMC3974565 DOI: 10.1111/hel.12052] [Citation(s) in RCA: 82] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
OBJECTIVE Levofloxacin has been proposed to replace clarithromycin for Helicobacter pylori treatment. Seven- and 10-day fluoroquinolone triple therapies have generally failed to achieve cure rates of ≥90%, whereas 14-day therapy has achieved 95% success. The aim was to assess the efficacy and effect of fluoroquinolone resistance on 14-day levofloxacin-containing triple therapy with or without the addition of bismuth. DESIGN Helicobacter pylori-positive patients with functional dyspepsia or healed peptic ulcers were randomized to receive lansoprazole 30 mg b.i.d., amoxicillin 1000 mg b.i.d., and levofloxacin 500 mg daily with (B-LAL) or without (LAL) bismuth potassium citrate 220 mg b.i.d. for 14 days. Eradication was assessed by ¹³C-urea breath testing 4 weeks after completing treatment. Antimicrobial susceptibility was by the agar dilution method. Success was defined as PP success ≥90%. RESULTS A total of 152 of 161 patients (81 LAL and 80 B-LAL) enrolled completed treatment. The PP rates were 94.6% (70/74; 95% CI, 86.9-97.9%) with B-LAL and 85.9% (95% CI, 76.5-91.9%) with LAL (p = .07); the ITT eradication rates were 87.5% (95% CI, 78.5-93.1%) with B-LAL and 82.7% (95% CI, 73-89.4%) with LAL (p = .39). Levofloxacin resistance was present in 30.3%. Treatment success was excellent with susceptible strains (97.5%) versus resistant strains (70.6%) for B-LAL and 97.3% versus 37.5% for LAL, respectively. CONCLUSIONS Fourteen-day fluoroquinolone therapy was highly effective when fluoroquinolone resistance rates are <12%. The addition of bismuth maintained effectiveness with fluoroquinolone resistance as high as 25%.
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Affiliation(s)
- Jingxian Liao
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - Qing Zheng
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - Xiao Liang
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - Wei Zhang
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - Qinjuan Sun
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - Wenzhong Liu
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - Shudong Xiao
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
| | - David Y. Graham
- Department of Medicine, Michael E. DeBakey VA Medical Center, Houston, TX, USA
| | - Hong Lu
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
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Su P, Li Y, Li H, Zhang J, Lin L, Wang Q, Guo F, Ji Z, Mao J, Tang W, Shi Z, Shao W, Mao J, Zhu X, Zhang X, Tong Y, Tu H, Jiang M, Wang Z, Jin F, Yang N, Zhang J. Antibiotic resistance of Helicobacter pylori isolated in the Southeast Coastal Region of China. Helicobacter 2013; 18:274-9. [PMID: 23418857 DOI: 10.1111/hel.12046] [Citation(s) in RCA: 128] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND The resistance of Helicobacter pylori (H. pylori) to antibiotics is increasing worldwide, lowering its efficacy in current eradication therapies. This study evaluated H. pylori resistance to antibiotics in the southeast coastal region of China and suggests appropriate alternatives. MATERIALS AND METHODS Seventeen thousand seven hundred and thirty one H. pylori strains were collected from eight areas of two provinces in coastal southeast China from 2010 to 2012. The resistance of these strains to six antibiotics was tested using the agar dilution method. RESULTS The resistance rates to clarithromycin, metronidazole, levofloxacin, amoxicillin, gentamicin and furazolidone were 21.5, 95.4, 20.6, 0.1, 0.1 and 0.1%, respectively. Double, triple and quadruple antibacterial resistant percentages were 25.5, 7.5 and 0.1%, respectively. A positive association between the resistance to levofloxacin and to clarithromycin was found, but there was a negative correlation in the resistances to levofloxacin and to metronidazole. CONCLUSIONS The prevalence of H. pylori resistance to clarithromycin, metronidazole, levofloxacin and multiple antibiotics in coastal southeast China is high. Choice of therapy should be individualized based on a susceptibility test in this region of the country.
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Affiliation(s)
- Peng Su
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
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Liang X, Xu X, Zheng Q, Zhang W, Sun Q, Liu W, Xiao S, Lu H. Efficacy of bismuth-containing quadruple therapies for clarithromycin-, metronidazole-, and fluoroquinolone-resistant Helicobacter pylori infections in a prospective study. Clin Gastroenterol Hepatol 2013; 11:802-7.e1. [PMID: 23376004 DOI: 10.1016/j.cgh.2013.01.008] [Citation(s) in RCA: 119] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2012] [Revised: 01/03/2013] [Accepted: 01/14/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We assessed the efficacy and safety of 4 bismuth-containing quadruple regimens as empiric therapies for Helicobacter pylori infections in patients who did not respond to previous treatment. METHODS We performed a prospective single-center study of 424 patients with H pylori infection that was not eradicated by previous therapies. Patients were assigned randomly to groups given lansoprazole (30 mg twice daily) and bismuth potassium citrate (220 mg twice daily), along with 500 mg tetracycline and 400 mg metronidazole 4 times daily (LBTM), 500 mg tetracycline and 100 mg furazolidone 3 times daily (LBTF), 1000 mg amoxicillin 3 times and 500 mg tetracycline 4 times daily (LBAT), or 1000 mg amoxicillin and 100 mg furazolidone 3 times daily (LBAF). Eradication was assessed by a (13)C-urea breath test. Antimicrobial susceptibility was assessed in 188 patients by the agar dilution method. RESULTS Per-protocol rates of H pylori eradication were greater than 90% for all regimens: 93.1% for LBTM (95% confidence interval [CI], 88.1%-98.0%), 96.1% for LBTF (95% CI, 92.4%-99.8%), 94.6% for LBAT (95% CI, 90.0%-99.2%), and 99.0% for LBAF (95% CI, 97.0%-100%). The intention-to-treat response rates were 87.9% for LBTM (95% CI, 81.7%-94.0%), 91.7% for LBTF (95% CI, 87.1%-96.3%), 83.8% for LBAT (95% CI, 76.8%-90.9%), and 95.2% for LBAF (95% CI, 91.1%-99.3%). Significantly more patients had infections eradicated by furazolidone-containing regimens than nonfurazolidone regimens (P = .01). Side effects occurred in 33.6% of subjects and occurred significantly more frequently in the LBTM group than the other 3 groups (vs LBTF, P = .006; vs LBAT, P = .003; vs LBAF, P = .02). Metronidazole resistance was 96.8%; no isolates were resistant to amoxicillin, tetracycline, or furazolidone. CONCLUSIONS Four bismuth-containing quadruple therapies achieved greater than 90% eradication of H pylori in patients who did not respond to previous treatment, including patients with metronidazole resistance. For patients allergic to penicillin, tetracycline and either metronidazole- or furazolidone-containing regimens are recommended. ClincialTrials.gov number, NCT01668927.
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Affiliation(s)
- Xiao Liang
- GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai, China
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High Helicobacter pylori resistance to metronidazole and clarithromycin in Brazilian children and adolescents. J Pediatr Gastroenterol Nutr 2013; 56:645-8. [PMID: 23403439 DOI: 10.1097/mpg.0b013e31828b3669] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE The aim of the present study was to assess the primary and secondary resistance of Helicobacter pylori strains to clarithromycin, amoxicillin, furazolidone, tetracycline, and metronidazole, the conventional antibiotics presently used in Brazilian children and adolescents. METHODS Seventy-seven consecutive H pylori strains, 71 of 77 strains obtained from patients without previous eradication treatment for H pylori infection, and 6 strains from patients in whom previous eradication treatment had failed. RESULTS Global rate of resistance was 49.3% (38/77): 40% of strains were resistant to metronidazole, 19.5% to clarithromycin, and 10.4% to amoxicillin. All of the tested H pylori strains were susceptible to furazolidone and tetracycline. Multiple resistance were detected in 18.2% (14/77 patients) of the strains: 6 of 14 (43%) simultaneously resistant to clarithromycin and metronidazole; 5 of 14 (36%) to amoxicillin and metronidazole; 2 of 14 (14%) to amoxicillin, clarithromycin, and metronidazole; and 1 of 14 (7%) to clarithromycin and amoxicillin. CONCLUSIONS The high resistance rate to metronidazole and clarithromycin observed in clinical H pylori isolates can exclude these antimicrobials in empirical eradication treatment in Brazil. Otherwise, furazolidone and tetracycline presented no resistance. Properly assessing the risks and benefits, these 2 antimicrobials and their derivatives could be used in empirical eradication schedules, both associated with amoxicillin, which showed a low resistance rate despite its wide use in pediatric patients.
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Liu WZ, Xie Y, Cheng H, Lu NH, Hu FL, Zhang WD, Zhou LY, Chen Y, Zeng ZR, Wang CW, Xiao SD, Pan GZ, Hu PJ. Fourth Chinese National Consensus Report on the management of Helicobacter pylori infection. J Dig Dis 2013; 14:211-21. [PMID: 23302262 DOI: 10.1111/1751-2980.12034] [Citation(s) in RCA: 89] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
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- Department of Gastroenterology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Cosme A, Montes M, Martos M, Gil I, Mendarte U, Salicio Y, Piñeiro L, Recasens M, Ibarra B, Sarasqueta C, Bujanda L. Usefulness of antimicrobial susceptibility in the eradication of Helicobacter pylori. Clin Microbiol Infect 2013; 19:379-383. [DOI: 10.1111/j.1469-0691.2012.03844.x] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/19/2023]
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Ang TL, Wang L, Ang D, Chiam P, Fock KM, Teo EK. Is there still a role for empiric first-line triple therapy using proton pump inhibitor, amoxicillin and clarithromycin for Helicobacter pylori infection in Singapore? Results of a time trend analysis. J Dig Dis 2013; 14:100-4. [PMID: 23253473 DOI: 10.1111/1751-2980.12024] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE This study was aimed to assess whether the efficacy of one-week triple therapy comprising of proton pump inhibitor, amoxicillin and clarithromycin (PPI/A/C) on Helicobacter pylori (H. pylori) infection in Singapore has decreased over the duration from 2005 to 2010. METHODS The clinical data of H. pylori-positive patients treated with one-week PPI/A/C in 2005 and 2010 were reviewed retrospectively using a registry database. The primary endpoint was the difference in treatment success rate. RESULTS A total of 465 patients (n = 174 in 2005 and n = 291 in 2010) were analyzed. In 2010, compared with 2005, the mean age of patients was younger (47 vs 56 years, P < 0.001) and the proportion of foreigners was higher (19.9% vs 5.7%, P < 0.001). The success rate of H. pylori eradication remained similar over the two time periods (90.2% in 2005 vs 88.7% in 2010, P = 0.597). Multinomial logistic regression revealed that mean age, gender, diagnosis and nationality had no impact on the success of H. pylori eradication. CONCLUSIONS From 2005 to 2010, there was no significant decrease in the efficacy of one-week PPI/A/C for the treatment of H. pylori infection. This treatment regime remained an effective first-line therapy for H. pylori infection in Singapore.
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Affiliation(s)
- Tiing Leong Ang
- Department of Gastroenterology, Changi General Hospital, Singapore.
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Qian J, Ye F, Zhang J, Yang YM, Tu HM, Jiang Q, Shang L, Pan XL, Shi RH, Zhang GX. Levofloxacin-containing triple and sequential therapy or standard sequential therapy as the first line treatment for Helicobacter pylori eradication in China. Helicobacter 2012; 17:478-485. [PMID: 23067317 DOI: 10.1111/j.1523-5378.2012.00993.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
AIMS To compare the efficacy and the adverse effects of levofloxacin-containing triple therapy, standard sequential therapy, and levofloxacin-containing sequential therapy as first-line treatment for Helicobacter pylori eradication. METHODS Three hundred and forty-five naive H. pylori-positive patients were randomized to receive levofloxacin-containing 7-day triple therapy (Levo triple, i.e., esomeprazole, 20 mg, twice daily, amoxicillin, 1 g, twice daily, and levofloxacin, 500 mg, once daily for 7 days, n = 114), standard sequential therapy (SST-10, 5-day esomeprazole, 20 mg, twice daily and amoxicillin, 1 g, twice daily followed by 5-day esomeprazole, 20 mg, twice daily, clarithromycin, 500 mg, twice daily and tinidazole, 500 mg, twice daily for 5 days, n = 115) or levofloxacin-containing sequential therapy (Levo-ST-10, 5-day esomeprazole, 20 mg, twice daily and amoxicillin, 1 g, twice daily for 5 days followed by 5-day esomeprazole, 20 mg, twice daily, levofloxacin, 500 mg, once daily and tinidazole, 500 mg, twice daily, n = 116). Eradication was confirmed by a (13) C-urea breath test 4 weeks after completion of treatment. RESULTS Intention to treat (ITT) eradication rates were 78.1% (95% CI: 69.4, 85.3%), 78.3% (95% CI: 69.6, 85.4%), and 82.8% (95% CI: 74.6, 89.1%) for Levo triple, SST-10, Levo-ST-10, respectively (p = .599). Per protocol (PP) eradication rates were 80.9% (95% CI: 72.3, 87.8%), 82.6% (95% CI: 74.1, 89.2%), and 86.5% (95% CI: 78.7, 92.2%), respectively, for the three therapies (p = .513). Overall, 3.8% experienced mild to moderate adverse events; the rates were 1.75, 4.35, and 5.17%, respectively, in the three groups (p = .325). CONCLUSIONS Standard sequential therapy and 7-day levofloxacin triple therapy produced unacceptably therapeutic efficacy in China. Only levofloxacin-containing sequential therapy achieved borderline acceptable result. None of the regimens tested reliably achieved 90% or greater therapeutic efficacy in China.
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Affiliation(s)
- Juan Qian
- Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
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Du YQ, Su T, Fan JG, Lu YX, Zheng P, Li XH, Guo CY, Xu P, Gong YF, Li ZS. Adjuvant probiotics improve the eradication effect of triple therapy for Helicobacter pylori infection. World J Gastroenterol 2012; 18:6302-6307. [PMID: 23180952 PMCID: PMC3501780 DOI: 10.3748/wjg.v18.i43.6302] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2012] [Revised: 09/10/2012] [Accepted: 09/12/2012] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate whether the addition of probiotics can improve the eradication effect of triple therapy for Helicobacter pylori (H. pylori) infection. METHODS This open randomized trial recruited 234 H. pylori positive gastritis patients from seven local centers. The patients were randomized to one-week standard triple therapy (omeprazole 20 mg bid, clarithromycin 500 mg bid, and amoxicillin 1000 mg bid; OCA group, n = 79); two weeks of pre-treatment with probiotics, containing 3 × 10(7)Lactobacillus acidophilus per day, prior to one week of triple therapy (POCA group, n = 78); or one week of triple therapy followed by two weeks of the same probiotics (OCAP group, n = 77). Successful eradication was defined as a negative C13 or C14 urease breath test four weeks after triple therapy. Patients were asked to report associated symptoms at baseline and during follow-up, and side effects related to therapy were recorded. Data were analyzed by both intention-to-treat (ITT) and per-protocol (PP) methods. RESULTS PP analysis involved 228 patients, 78 in the OCA, 76 in the POCA and 74 in the OCAP group. Successful eradication was observed in 171 patients; by PP analysis, the eradication rates were significantly higher (P = 0.007 each) in the POCA (62/76; 81.6%, 95% CI 72.8%-90.4%) and OCAP (61/74; 82.4%, 95% CI 73.6%-91.2%) groups than in the OCA group (48/78; 61.5%, 95% CI 50.6%-72.4%). ITT analysis also showed that eradication rates were significantly higher in the POCA (62/78; 79.5%, 95% CI 70.4%-88.6%) and OCAP (61/77; 79.2%, 95% CI 70%-88.4%) groups than in the OCA group (48/79; 60.8%, 95% CI 49.9%-71.7%), (P = 0.014 and P = 0.015). The symptom relieving rates in the POCA, OCAP and OCA groups were 85.5%, 89.2% and 87.2%, respectively. Only one of the 228 patients experienced an adverse reaction. CONCLUSION Administration of probiotics before or after standard triple therapy may improve H. pylori eradication rates.
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