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      Understanding treatment guidelines with bismuth and non-bismuth quadruple Helicobacter pylori eradication therapies

      1 , 2 , 3
      Expert Review of Anti-infective Therapy
      Informa UK Limited

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          Abstract

          <div class="section"> <a class="named-anchor" id="S1"> <!-- named anchor --> </a> <h5 class="section-title" id="d5026399e147">Introduction:</h5> <p id="P1">Recent <i>Helicobacter pylori</i> treatment guidelines recommend the 4-drug combinations bismuth quadruple therapy and concomitant therapy. </p> </div><div class="section"> <a class="named-anchor" id="S2"> <!-- named anchor --> </a> <h5 class="section-title" id="d5026399e155">Areas covered:</h5> <p id="P2">We review antimicrobial therapy for <i>H. pylori</i> in the context of antimicrobial therapy in general and specifically in relation to good antimicrobial stewardship (defined as optimal selection, dose, and duration of an antimicrobial that results in the best clinical outcome for the treatment of infection, with minimal toxicity to the patient and minimal impact on subsequent resistance). </p> </div><div class="section"> <a class="named-anchor" id="S3"> <!-- named anchor --> </a> <h5 class="section-title" id="d5026399e163">Expert commentary:</h5> <p id="P3">The lack of regional and local <i>H. pylori</i> susceptibility data prevents implementation of susceptibility-based antimicrobial therapy and forces compromises. Bismuth quadruple therapy employing at least 1,500 mg of metronidazole for 14 days is effective despite metronidazole resistance. The main drawback is side effects causing reduced adherence. Versions where amoxicillin replaces metronidazole or tetracycline also appear effective. It is likely that bismuth quadruple therapy can be simplified by giving bismuth and tetracycline b.i.d., possibly with fewer side effects. Concomitant therapy (a proton pump inhibitor, metronidazole, clarithromycin, amoxicillin) is ineffective with dual clarithromycin-metronidazole resistance and all patients receive at least one unnecessary antibiotic thus promoting antimicrobial resistance worldwide. Concomitant therapy should be abandoned when susceptibility testing becomes widespread or an alternate becomes available. </p> </div>

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          Most cited references39

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          The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults.

          Helicobacter pylori infection is increasingly difficult to treat. The purpose of these consensus statements is to provide a review of the literature and specific, updated recommendations for eradication therapy in adults.
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            General Principles of Antimicrobial Therapy

            Antimicrobial agents are some of the most widely, and often injudiciously, used therapeutic drugs worldwide. Important considerations when prescribing antimicrobial therapy include obtaining an accurate diagnosis of infection; understanding the difference between empiric and definitive therapy; identifying opportunities to switch to narrow-spectrum, cost-effective oral agents for the shortest duration necessary; understanding drug characteristics that are peculiar to antimicrobial agents (such as pharmacodynamics and efficacy at the site of infection); accounting for host characteristics that influence antimicrobial activity; and in turn, recognizing the adverse effects of antimicrobial agents on the host. It is also important to understand the importance of antimicrobial stewardship, to know when to consult infectious disease specialists for guidance, and to be able to identify situations when antimicrobial therapy is not needed. By following these general principles, all practicing physicians should be able to use antimicrobial agents in a responsible manner that benefits both the individual patient and the community.
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              Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study.

              Resistance to antibiotics is a major public-health problem, and studies that link antibiotic use and resistance have shown an association but not a causal effect. We used the macrolides azithromycin and clarithromycin to investigate the direct effect of antibiotic exposure on resistance in the oral streptococcal flora of healthy volunteers. Volunteers were treated with azithromycin (n=74), clarithromycin (74), or placebo (76) in a randomised, double-blind trial. Pharyngeal swabs were obtained before and after administration of study treatment through 180 days. The proportion of streptococci that were macrolide resistant was assessed and the molecular basis of any change in resistance investigated. Analyses were done on an intent-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT00354952. The number of dropouts (n=20) was much the same in all groups until day 42; dropouts increased substantially at day 180 (105). Both macrolides significantly increased the proportion of macrolide-resistant streptococci compared with the placebo at all points studied, peaking at day 8 in the clarithromycin group (mean increase 50.0%, 95% CI 41.7-58.2; p<0.0001) and at day 4 in the azithromycin group (53.4%, 43.4-63.5; p<0.0001). The proportion of macrolide-resistant streptococci was higher after azithromycin treatment than after clarithromycin use, with the largest difference between the two groups at day 28 (17.4% difference, 9.2-25.6; p<0.0001). Use of clarithromycin, but not of azithromycin, selected for the erm(B) gene, which confers high-level macrolide resistance. This study shows that, notwithstanding the different outcomes of resistance selection, macrolide use is the single most important driver of the emergence of macrolide resistance in vivo. Physicians prescribing antibiotics should take into account the striking ecological side-effects of such antibiotics.
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                Author and article information

                Journal
                Expert Review of Anti-infective Therapy
                Expert Review of Anti-infective Therapy
                Informa UK Limited
                1478-7210
                1744-8336
                August 21 2018
                September 02 2018
                August 23 2018
                September 02 2018
                : 16
                : 9
                : 679-687
                Affiliations
                [1 ] Department of Medicine, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, TX, USA
                [2 ] Dipartimento di Medicina Clinica e Sperimentale, Clinica Medica, University of Sassari, Sassari, Italy
                [3 ] Key Laboratory of Gastroenterology &amp; Hepatology, Ministry of Health, GI Division, Ren Ji Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai Institution of Digestive Disease, Shanghai, China
                Article
                10.1080/14787210.2018.1511427
                6309304
                30102559
                89ef4fa8-c807-4205-b841-57108cccdd3d
                © 2018
                History

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