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      Levofloxacin-containing triple therapy versus bismuth-based quadruple therapy as regimens for second line anti- Helicobacter pylori

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          Abstract

          Background:

          Although the prevalence of Helicobacter pylori infection decreased following the hygiene promotion and application of proper anti- H.pylori treatments, unfortunately gradual increase is reported in treatment failure; hence, application of a proper treatment regimen as a second-line therapy is of great importance.

          Methods:

          In the current randomized, clinical trial, a total of 120 patients with peptic ulcers who failed to respond to treatment were enrolled. In the OLA group, a regimen of omeprazole 40 mg/day, levofloxacin 1 g/day, and amoxicillin 2 g/ day was prescribed; however, a regimen of omeprazole 40 mg/day, bismuth sub-citrate 480 mg/day, furazolidone 400 mg/day, and amoxicillin 2 g/day was administered to the OFAB group. Both groups were treated for 2 weeks, and 6 weeks after the treatment, the urea breath test (UBT) was performed in the subjects. Collected data were analyzed with SPSS Version 18. At the end, 58 patients in group OLA and 57 patients in the OFAB group were analyzed.

          Results:

          According to the results of the current study, 96.7% of the subjects in the OLA and 95% in the OFAB groups completed the treatment course and the eradication rates were 86.7% and 78.3% in the OLA and OFAB groups, respectively (P=0.23). Treatment side effects were observed in 51.7% and 11.7% of the subjects in the OLA and OFAB groups, respectively (P<0.01).

          Conclusion:

          Both regimens were applicable as the second-line therapy due to insignificant difference between the results of the 2 groups; however, OLA regimen was superior to OFAB, due to lower side effects.

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          Most cited references25

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          Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection.

          The Asia-Pacific Consensus Conference was convened to review and synthesize the most current information on Helicobacter pylori management so as to update the previously published regional guidelines. The group recognized that in addition to long-established indications, such as peptic ulcer disease, early mucosa-associated lymphoid tissue (MALT) type lymphoma and family history of gastric cancer, H. pylori eradication was also indicated for H. pylori infected patients with functional dyspepsia, in those receiving long-term maintenance proton pump inhibitor (PPI) for gastroesophageal reflux disease, and in cases of unexplained iron deficiency anemia or idiopathic thrombocytopenic purpura. In addition, a population 'test and treat' strategy for H. pylori infection in communities with high incidence of gastric cancer was considered to be an effective strategy for gastric cancer prevention. It was recommended that H. pylori infection should be tested for and eradicated prior to long-term aspirin or non-steroidal anti-inflammatory drug therapy in patients at high risk for ulcers and ulcer-related complications. In Asia, the currently recommended first-line therapy for H. pylori infection is PPI-based triple therapy with amoxicillin/metronidazole and clarithromycin for 7 days, while bismuth-based quadruple therapy is an effective alternative. There appears to be an increasing rate of resistance to clarithromycin and metronidazole in parts of Asia, leading to reduced efficacy of PPI-based triple therapy. There are insufficient data to recommend sequential therapy as an alternative first-line therapy in Asia. Salvage therapies that can be used include: (i) standard triple therapy that has not been previously used; (ii) bismuth-based quadruple therapy; (iii) levofloxacin-based triple therapy; and (iv) rifabutin-based triple therapy. Both CYP2C19 genetic polymorphisms and cigarette smoking can influence future H. pylori eradication rates.
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            Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial.

            Helicobacter pylori is associated with benign and malignant diseases of the upper gastrointestinal tract, and increasing antibiotic resistance has made alternative treatments necessary. Our aim was to assess the efficacy and safety of a new, single-capsule treatment versus the gold standard for H pylori eradication. We did a randomised, open-label, non-inferiority, phase 3 trial in 39 sites in Europe, comparing the efficacy and safety of 10 days of quadruple therapy with omeprazole plus a single three-in-one capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline (quadruple therapy) versus 7 days of omeprazole, amoxicillin, and clarithromycin (standard therapy) in adults with recorded H pylori infection. Patients were randomly assigned treatment according to a predetermined list independently generated by Quintiles Canada (Ville St-Laurent, QC, Canada). Our study was designed as a non-inferiority trial but was powered to detect superiority. Our primary outcome was H pylori eradication, established by two negative (13)C urea breath tests at a minimum of 28 and 56 days after the end of treatment. Our assessment for non-inferiority was in the per-protocol population, with subsequent assessment for superiority in the intention-to-treat population (ie, all participants randomly assigned treatment). This study is registered with ClinicalTrials.gov, number NCT00669955. 12 participants were lost to follow-up and 101 were excluded from the per-protocol analysis. In the per-protocol population (n=339), the lower bound of the CI for treatment with quadruple therapy was greater than the pre-established non-inferiority margin of -10% (95% CI 15·1-32·3; p<0·0001). In the intention-to-treat population (n=440), eradication rates were 80% (174 of 218 participants) in the quadruple therapy group versus 55% (123 of 222) in the standard therapy group (p<0·0001). Safety profiles for both treatments were similar; main adverse events were gastrointestinal and CNS disorders. Quadruple therapy should be considered for first-line treatment in view of the rising prevalence of clarithromycin-resistant H pylori, especially since quadruple therapy provides superior eradication with similar safety and tolerability to standard therapy. Axcan Pharma Inc. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Meta-analysis: the effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapies for Helicobacter pylori.

              Information regarding the effects of drug resistance on therapies for Helicobacter pylori is limited. To determine the effect of drug resistance on the efficacy of first-line treatment regimens for H. pylori and identify the most efficacious treatments in the presence of drug resistance. We searched for studies using the keywords: 'Helicobacter pylori','resistance' and 'treatment' or 'therapy'. Multilevel meta-regression models were used to determine the effect of drug resistance on treatment efficacy. We analysed data from 93 studies with 10,178 participants. For triple therapies, clarithromycin resistance had a greater effect on treatment efficacy than nitroimidazole resistance. Metronidazole resistance reduced efficacy by 26% in triple therapies containing a nitroimidazole, tetracycline and bismuth, while efficacy was reduced by only 14% when a gastric acid inhibitor was added to the regimen. Quadruple therapies containing both clarithromycin and metronidazole were the most efficacious; >80% of H. pylori infections were consistently eradicated with these regimens. Drug resistance was a strong predictor of efficacy across triple therapies for the eradication of H. pylori in adults. Resistance to either clarithromycin or metronidazole, but not both simultaneously, may be overcome by using quadruple therapies, especially those containing both clarithromycin and metronidazole.
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                Author and article information

                Journal
                Caspian J Intern Med
                Caspian J Intern Med
                CJIM
                Caspian Journal of Internal Medicine
                Babol University of Medical Sciences (Babol, Iran )
                2008-6164
                2008-6172
                Spring 2019
                : 10
                : 2
                : 211-216
                Affiliations
                [1 ]Golestan Research Center of Gastroenterology and Hepatology-GRCGH (GOUMS), Golestan University of Medical Sciences, Gorgan, Iran
                [2 ]Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Sciences, Qom, Iran
                [3 ]Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
                Author notes
                [* ]Correspondence: Jamshid Vafaeimanesh, Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Sciences, Qom, Iran. E-mail: jvafaeemanesh@yahoo.com, Tel: 0098 2536122949, Fax: 0098 2536122949
                Article
                10.22088/cjim.10.2.211
                6619475
                55a16d46-8c28-4dd6-987b-46ec410169d6

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 February 2018
                : 7 December 2018
                : 30 December 2018
                Categories
                Original Article

                helicobacter pylori,second-line therapy,levofloxacin-based triple therapy,bismuth-based quadruple therapy

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