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• W1966243555 abstract "Eradication therapy for Helicobacter pylori is recommended in a number of clinical conditions. In this article, we discuss the epidemiology and cellular mechanisms that result in antimicrobial resistance, the results of current eradication therapies, and new approaches to the management of Helicobacter pylori infection. Eradication therapy for Helicobacter pylori is recommended in a number of clinical conditions. In this article, we discuss the epidemiology and cellular mechanisms that result in antimicrobial resistance, the results of current eradication therapies, and new approaches to the management of Helicobacter pylori infection. Helicobacter pylori is an organism that has had an intimate association with mankind for many generations. Recent studies suggest that H pylori may have spread from east Africa with human migration approximately 58,000 years ago.1Linz B. Balloux F. Moodley Y. et al.An African origin for the intimate association between humans and Helicobacter pylori.Nature. 2007; 445: 915-918Crossref PubMed Scopus (405) Google Scholar The discovery of H pylori by Warren and Marshall and the development of effective treatment for this infection has resulted in a remarkable change in the management of upper gastrointestinal disorders with curative antibiotic therapy becoming available for low-grade gastric mucosa-associated lymphoid tissue lymphomas and H pylori-related peptic ulcers. Treatment regimens for H pylori that have been used over the past decade are declining in efficacy, and the treatment of H pylori infection is bedeviled by drug-resistant strains of H pylori. In this article, we discuss the clinical and basic issues involved in H pylori eradication, the mechanism of antibiotic delivery to the mucus layer of the stomach, the primary and secondary treatment strategies, the causes of treatment failure, and the mechanisms for the development of antimicrobial resistance.H pylori is a member of a group of bacteria adapted to life in the mucus of the digestive tract of vertebrates. Its specific characteristics include its morphology (spiral shaped, flagellated) and metabolism (microaerobic, asaccharolytic). Gastric Helicobacters have probably evolved from a gut bacterial ancestor when the stomach appeared in vertebrates, and H pylori is the Helicobacter specific to humans.Indications for the Treatment of H pylori InfectionIndications for H pylori eradication that were developed by an international consensus of experts (Maastricht III Consensus Report) are listed in Table 1.2Malfertheiner P. Megraud F. O’Morain C. et al.Current concepts in the management of Helicobacter pylori infection—The Maastricht III Consensus Report.Gut. 2007; 56: 772-781Crossref PubMed Scopus (1330) Google Scholar Current US guidelines recommend testing and treatment for H pylori in patients with uninvestigated dyspepsia in areas in which the prevalence of H pylori is greater than 10%.3Talley N.J. Vakil N.B. Moayyedi P. American Gastroenterological Association technical review on the evaluation of dyspepsia.Gastroenterology. 2005; 129: 1756-1780Abstract Full Text Full Text PDF PubMed Scopus (233) Google Scholar, 4Talley N.J. Vakil N. Practice Parameters Committee of the American College of Gastroenterology Guidelines for the management of dyspepsia.Am J Gastroenterol. 2005; 100: 2324-2337Crossref PubMed Scopus (277) Google Scholar The Maastricht Consensus Group recognized the links between gastric cancer and H pylori and recommended further work in the area.2Malfertheiner P. Megraud F. O’Morain C. et al.Current concepts in the management of Helicobacter pylori infection—The Maastricht III Consensus Report.Gut. 2007; 56: 772-781Crossref PubMed Scopus (1330) Google Scholar Because of problems with antimicrobial resistance with current therapies and the lack of an effective vaccine, mass treatment strategies have not been implemented. North American practitioners should be aware that immigrants from parts of Central and South America (Costa Rica, Brazil) and the Far East (China, Japan, Korea, and Taiwan) are at high risk for gastric cancer, and obtaining a family history is particularly important in people from this part of the world.Table 1Indications for Helicobacter pylori EradicationDuodenal ulcerGastric ulcerAtrophic gastritisGastric MALT lymphomaNonulcer dyspepsiaUninvestigated dyspepsia (in areas with a prevalence >10%)Following resection of a gastric cancerFirst-degree relatives of patients with gastric cancerUnexplained iron-deficiency anemiaIdiopathic thrombocytopenic purpuraBefore commencing NSAID therapy in NSAID-naïve patientsPatients receiving long-term aspirin therapy who develop gastrointestinal bleedingPatient request (after a discussion of risks and benefits)NOTE. Information in Table taken from Malfertheiner et al.2Malfertheiner P. Megraud F. O’Morain C. et al.Current concepts in the management of Helicobacter pylori infection—The Maastricht III Consensus Report.Gut. 2007; 56: 772-781Crossref PubMed Scopus (1330) Google ScholarMALT, mucosa-associated lymphoid tissue; NSAID, nonsteroidal antiinflammatory drugs. Open table in a new tab Delivery of Antibiotics to H pyloriMost antibiotics are formulated for delivery to the small bowel to facilitate their absorption and consequently their blood-borne effects. The success of antimicrobial therapy for H pylori depends to a large extent on antimicrobial concentrations in the stomach. The principles of antimicrobial delivery to H pylori are important in understanding the rationale for various antimicrobial combinations that are used in clinical practice. They are illustrated in Figure 1.Ingestion of AntibioticsIngestion of antibiotics by patients is influenced by drug adverse effects and regimen complexity. Nausea and vomiting can limit drug ingestion (Figure 1). Regimens that require medications to be taken 4 times a day (quadruple therapy) are more likely to have adherence-related problems than twice-daily therapies.5Cockburn J. Gibberd R.W. Reid A.L. et al.Determinants of non-compliance with short-term antibiotic regimens.Br Med J (Clin Res Ed). 1987; 295: 814-818Crossref PubMed Google Scholar There is limited information on the effect of drug formulation on treatment efficacy, but studies with amoxicillin suggest that the liquid preparation has better delivery to all parts of the stomach than capsules.Luminal FactorsAntibiotics have varying stability at acid pH. Metronidazole is very stable in gastric juice at a pH of 2 and a pH of 7, with a half-life of over 800 hours. Amoxicillin is unstable at low pH, but its half-life is still 15 hours at a pH of 2. In contrast, clarithromycin is particularly sensitive to degradation with acid and has a half-life of less than 1 hour at a pH of 2.6Goddard A. Review article: factors influencing antibiotic transfer across the gastric mucosa.Aliment Pharmacol Ther. 1998; 12: 1175-1184Crossref PubMed Scopus (27) Google Scholar, 7Erah P. Goddard A. Barrett D. et al.The stability of amoxicillin, clarithromycin and metronidazole in gastric juice: relevance to the treatment of Helicobacter pylori infection.J Antimicrob Chemother. 1997; 39: 5-12Crossref PubMed Scopus (136) Google Scholar The use of proton pump inhibitors (PPI) in antimicrobial regimens that contain clarithromycin is particularly important in preventing degradation of clarithromycin by acid (Figure 1).Gastric PhysiologyThe gastric mucus layer acts as a barrier limiting the delivery of antibiotics to H pylori. In animal experiments, pronase, which digests gastric mucus, increases delivery of amoxicillin.8Sherwood P. Wibawa J. Atherton J. et al.Impact of acid secretion, gastritis and mucus thickness on gastric transfer of antibiotics in rats.Gut. 2002; 51: 490-494Crossref PubMed Scopus (18) Google Scholar There is little information on interventions to change the quality or thickness of the mucus layer in the treatment of H pylori infection. PPIs may also decrease the viscosity of gastric mucus, increasing the delivery of all antibiotics. Occluding the duodenum with a balloon to increase contact time of antibiotics with the gastric mucosa has been attempted in a small study and resulted in a rapid cure of H pylori infection.9Kihira K. Satoh K. Saifuku K. et al.Endoscopic topical therapy for the treatment of Helicobacter pylori infection.J Gastroenterol. 1996; 31: 66-68PubMed Google ScholarSystemic Delivery of Antibiotics to the StomachAntibiotics move across cells by lipid diffusion. They dissolve in the lipids of the cell membrane, and, then, passive transfer occurs by a concentration gradient.6Goddard A. Review article: factors influencing antibiotic transfer across the gastric mucosa.Aliment Pharmacol Ther. 1998; 12: 1175-1184Crossref PubMed Scopus (27) Google Scholar Drug ionization also plays a role. Unionized drugs cross membranes easily, whereas more polar molecules cross with difficulty. Metronidazole is predominantly unionized in plasma and therefore crosses the gastric mucosa easily into gastric juice with gastric acid secretion.6Goddard A. Review article: factors influencing antibiotic transfer across the gastric mucosa.Aliment Pharmacol Ther. 1998; 12: 1175-1184Crossref PubMed Scopus (27) Google Scholar Omeprazole decreases intragastric concentrations of metronidazole by reducing acid secretion but increases concentrations of all agents by decreasing gastric volume.10Goddard A. Jessa M. Barrett D. et al.Effect of omeprazole on the distribution of metronidazole, amoxicillin and clarithromycin in human gastric juice.Gastroenterology. 1996; 111: 358-367Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar Some studies have shown that acid inhibitors, such as omeprazole, increase the concentration of clarithromycin in gastric tissue, but other studies have not.11Gustavson L. Kaiser J. Edmonds A.M. Locke C. et al.Effect of omeprazole on gastric concentrations of clarithromycin in plasma and gastric tissue at steady state.Antimicrob Agents Chemother. 1992; 36: 1147-1150Crossref PubMed Google Scholar, 12Pedrazzoli J. Calafatti S. Ortiz R. et al.Transfer of clarithromycin to gastric juice is enhanced by omeprazole in Helicobacter pylori-infected individuals.Scand J Gastroenterol. 2001; 36: 1248-1253Crossref PubMed Scopus (16) Google ScholarTreatment Strategies for H pyloriOverviewThe treatment of H pylori infection has not changed significantly in the last decade, although promising alternatives have recently been suggested. At the present time, the treatment regimen recommended for worldwide use is triple therapy with PPI, amoxicillin, and clarithromycin.2Malfertheiner P. Megraud F. O’Morain C. et al.Current concepts in the management of Helicobacter pylori infection—The Maastricht III Consensus Report.Gut. 2007; 56: 772-781Crossref PubMed Scopus (1330) Google Scholar Dissatisfaction with this regimen is growing in most developed countries, and a new initial therapeutic strategy is needed. The alternatives to triple therapy include quadruple therapy, sequential therapy, and triple therapy using new antimicrobials such as levofloxacin, rifabutin, and furazolidone. Each of these is discussed in more detail below, and a strategy is suggested for management.Initial Management StrategiesPPI triple therapyA PPI combined with amoxicillin and clarithromycin is the most widely used form of therapy in the Western world. In areas where clarithromycin resistance rates are high, metronidazole may be substituted for clarithromycin. Eradication rates with triple therapy have been falling with rising resistance rates to commonly used antimicrobials, and a recent consensus group considered alternatives to triple therapy but eventually concluded that PPI-based triple therapy was still the initial treatment of choice.2Malfertheiner P. Megraud F. O’Morain C. et al.Current concepts in the management of Helicobacter pylori infection—The Maastricht III Consensus Report.Gut. 2007; 56: 772-781Crossref PubMed Scopus (1330) Google ScholarFigure 2 shows the rate of eradication with triple therapy in large, controlled trials in the United States.13Laine L. Fennerty M.B. Osato M. et al.Esomeprazole-based Helicobacter pylori eradication therapy and the effect of antibiotic resistance: results of three US multicenter, double-blind trials.Am J Gastroenterol. 2000; 95: 3393-3398Crossref PubMed Google Scholar, 14Laine L. Hunt R. El-Zimaity H. et al.Bismuth-based quadruple therapy using a single capsule of bismuth biskalcitrate, metronidazole, and tetracycline given with omeprazole versus omeprazole, amoxicillin, and clarithromycin for eradication of Helicobacter pylori in duodenal ulcer patients: a prospective, randomized, multicenter, North American trial.Am J Gastroenterol. 2003; 98: 562-567Crossref PubMed Scopus (137) Google Scholar, 15Laine L. Suchower L. Frantz J. et al.Twice-daily, 10-day triple therapy with omeprazole, amoxicillin, and clarithromycin for Helicobacter pylori eradication in duodenal ulcer disease: results of three multicenter, double-blind, United States trials.Am J Gastroenterol. 1998; 93: 2106-2112Crossref PubMed Scopus (58) Google Scholar, 16Fennerty M.B. Kovacs T.O. Krause R. et al.A comparison of 10 and 14 days of lansoprazole triple therapy for eradication of Helicobacter pylori.Arch Intern Med. 1998; 158: 1651-1656Crossref PubMed Scopus (60) Google Scholar, 17Bochenek W.J. Peters S. Fraga P.D. et al.Helicobacter pylori Pantoprazole Eradication (HELPPE) Study GroupEradication of Helicobacter pylori by 7-day triple-therapy regimens combining pantoprazole with clarithromycin, metronidazole, or amoxicillin in patients with peptic ulcer disease: results of two double-blind, randomized studies.Helicobacter. 2003; 8: 626-642Crossref PubMed Scopus (45) Google Scholar, 18Vakil N. Lanza F. Schwartz H. et al.Seven-day therapy for Helicobacter pylori in the United States.Aliment Pharmacol Ther. 2004; 20: 99-107Crossref PubMed Scopus (142) Google Scholar Note that the confidence intervals for eradication with 7-day triple therapy in the most recent trials have been as low as 57%–73% (Figure 2, Bochenek et al17Bochenek W.J. Peters S. Fraga P.D. et al.Helicobacter pylori Pantoprazole Eradication (HELPPE) Study GroupEradication of Helicobacter pylori by 7-day triple-therapy regimens combining pantoprazole with clarithromycin, metronidazole, or amoxicillin in patients with peptic ulcer disease: results of two double-blind, randomized studies.Helicobacter. 2003; 8: 626-642Crossref PubMed Scopus (45) Google Scholar) and 67%–79% (Figure 2, Vakil et al18Vakil N. Lanza F. Schwartz H. et al.Seven-day therapy for Helicobacter pylori in the United States.Aliment Pharmacol Ther. 2004; 20: 99-107Crossref PubMed Scopus (142) Google Scholar) for 10-day triple therapy. When an individual patient is treated in clinical practice, the eradication rate may be anywhere within this range. The duration of the triple therapy regimen has been the subject of debate. Early studies of 7-day therapy in the United States suggested that the results were poorer than in Europe, but these studies had low power and wide confidence intervals making accurate predictions impossible.19Laine L. Estrada R. Trujillo M. et al.Randomized comparison of differing periods of twice a day triple therapy for the eradication of Helicobacter pylori.Aliment Pharmacol Ther. 1996; 10: 1029-1033Crossref PubMed Google Scholar A head-to-head comparison of 7-day and 10-day therapy in the United States found numerical differences favoring 10-day therapy, but the comparisons between the groups met prespecified US Food and Drug Administration criteria for equivalence.18Vakil N. Lanza F. Schwartz H. et al.Seven-day therapy for Helicobacter pylori in the United States.Aliment Pharmacol Ther. 2004; 20: 99-107Crossref PubMed Scopus (142) Google Scholar A recent European study found no difference between 1 week and 2 weeks of PPI triple therapy.20Zagari R.M. Bianchi-Porro G. Fiocca R. et al.Comparison of 1 and 2 weeks of omeprazole, amoxicillin and clarithromycin treatment for Helicobacter pylori eradication: the HYPER Study.Gut. 2007; 56 (Epub October 6, 2006): 475-479Crossref PubMed Scopus (70) Google Scholar A review of controlled trials suggested that 14 days of treatment with triple therapy was superior to 7-day therapy (difference, 12%; 95% CI: 7%–17%).21Ford A. Moayyedi P. How can the current strategies for Helicobacter pylori eradication therapy be improved?.Can J Gastroenterol. 2003; 17: B36-B40PubMed Google Scholar At this point, it seems prudent to use at least 10 days of treatment in the United States.Figure 2Eradication rates in large US trials of PPI triple therapy. E, esomeprazole; A, amoxicillin; C, clarithromycin; O, omeprazole; B, Bismuth; M, metronidazole; T, tetracycline; L, lansoprazole; P, pantoprazole; R, rabeprazole. Usual doses: PPI, twice a day; clarithromycin, 500 mg twice a day; amoxicillin, 1 g twice a day. Esomeprazole was studied in a single daily dose. *Mean of 2 studies.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Bismuth-based triple/quadruple therapyBismuth triple (bismuth + metronidazole + tetracycline administered for 14 days) and quadruple (bismuth + metronidazole + tetracycline + PPI administered for 7–10 days) therapies are effective treatment strategies in areas in which metronidazole resistance is low, clarithromycin resistance is high, and cost considerations are paramount. Bismuth triple therapy administered for 14 days has been available for over a decade but has had limited success with physicians and patients in the United States or in other Western countries. The principal problem with this regimen is the large number of tablets/capsules that need to be taken and the duration of therapy and its complexity. To improve adherence, convenience packs that contain all the medications on a plasticized sheet have been developed. The major advantage of the bismuth triple therapy regimen is that it is inexpensive and can be used in regions of the world in which cost is the major consideration. Another advantage is that this regimen remains effective in areas in which clarithromycin resistance is high. A large, randomized, controlled trial evaluated bismuth triple therapy administered for 14 days and compared it with 7-day PPI triple therapy (PPI + amoxicillin + clarithromycin) and 7-day quadruple therapy (bismuth + metronidazole + tetracycline + PPI).22Katelaris P.H. Forbes G.M. Talley N.J. et al.A randomized comparison of quadruple and triple therapies for Helicobacter pylori eradication: the QUADRATE Study.Gastroenterology. 2002; 123: 1763-1769Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar Eradication rates were similar with PPI triple therapy (78%) and quadruple therapy (82%), and both were significantly better than 14-day bismuth triple therapy (69%). Nonadherence with therapy (15%) was significantly greater with bismuth triple therapy administered for 14 days, and moderate-severe adverse events were very common (45%). Quadruple therapy administered for 7–10 days (the duration should depend on location and local experience) is therefore preferable to bismuth triple therapy administered for 14 days. In another randomized, controlled trial in Spain, 7-day PPI triple therapy was similar to quadruple therapy in the eradication of H pylori.23Calvet X. Ducons J. Guardiola J. et al.Group for Eradication Studies from Catalonia and Aragon (Gresca)One-week triple vs. quadruple therapy for Helicobacter pylori infection—a randomized trial.Aliment Pharmacol Ther. 2002; 16: 1261-1267Crossref PubMed Scopus (49) Google Scholar The dose of bismuth should be based on the preparation used. In the United States, the most frequently used preparation is bismuth subsalicylate (150 mg bismuth per tablet), which is administered in a dose of 2 tablets 4 times a day along with tetracycline 500 mg and metronidazole 250 mg also administered 4 times a day. The patient should be instructed to chew the bismuth tablets before swallowing but to swallow the metronidazole and tetracycline without chewing.A relatively new development with quadruple therapy has been the development of a single capsule preparation of bismuth biskalcitrate with metronidazole and tetracycline. Although it reduces the number of pills that need to be taken, 3 tablets still need to be taken 4 times a day and a PPI needs to be taken separately twice a day. Results have been promising, with an eradication rate of 93% by intent-to-treat analysis in Europe and 87.7% in the United States for 10-day therapy.14Laine L. Hunt R. El-Zimaity H. et al.Bismuth-based quadruple therapy using a single capsule of bismuth biskalcitrate, metronidazole, and tetracycline given with omeprazole versus omeprazole, amoxicillin, and clarithromycin for eradication of Helicobacter pylori in duodenal ulcer patients: a prospective, randomized, multicenter, North American trial.Am J Gastroenterol. 2003; 98: 562-567Crossref PubMed Scopus (137) Google Scholar, 24O’Morain C. Borody T. Farley A. et al.International multicentre studyEfficacy and safety of single-triple capsules of bismuth biskalcitrate, metronidazole and tetracycline, given with omeprazole, for the eradication of Helicobacter pylori: an international multicentre study.Aliment Pharmacol Ther. 2003; 17: 415-420Crossref PubMed Scopus (72) Google Scholar In the US trial, the results were comparable with 10-day PPI triple therapy. The treatment remained effective despite the high observed resistance rate for metronidazole in the United States (40%), although the absolute number of patients with resistance was small (n = 51). A meta-analysis evaluated quadruple therapies and found that there was no significant difference between PPI triple therapy and quadruple therapy when clarithromycin resistance rates were less than 15%.25Fischbach L.A. van Zanten S. Dickason J. Meta-analysis: the efficacy, adverse events, and adherence related to first-line anti-Helicobacter pylori quadruple therapies.Aliment Pharmacol Ther. 2004; 20: 1071-1082Crossref PubMed Scopus (123) Google Scholar In patients with clarithromycin resistance however, quadruple therapy was significantly better than triple therapy. Bismuth-based quadruple therapy for 10 days is therefore a suitable salvage therapy of patients who have failed clarithromycin-based triple therapy.Whether quadruple therapy should replace PPI triple therapy as the initial treatment of choice is a matter of debate. A recent meta-analysis found only 4 studies of sufficient quality to allow comparisons and no statistically significant difference between PPI triple therapy and quadruple therapy.26Gene E. Calvet X. Azagra R. Triple vs. quadruple therapy for treating Helicobacter pylori infection: a meta-analysis.Aliment Pharmacol Ther. 2003; 17: 1137-1143Crossref PubMed Scopus (91) Google Scholar At the recent Maastricht International Consensus Conference of experts on H pylori, a proposal that PPI triple therapy be replaced with quadruple therapy was made but failed to generate sufficient support.2Malfertheiner P. Megraud F. O’Morain C. et al.Current concepts in the management of Helicobacter pylori infection—The Maastricht III Consensus Report.Gut. 2007; 56: 772-781Crossref PubMed Scopus (1330) Google Scholar Quadruple therapy is listed as an alternative first-line therapy to PPI triple therapy and should definitely be considered when a clarithromycin-based triple therapy regimen has failed or in areas in which clarithromycin resistance is particularly high. Another bismuth preparation, ranitidine bismuth citrate, is no longer available in the United States but has been shown to be effective in H pylori eradication in combination with clarithromycin and amoxicillin in a meta-analysis.27Gisbert J.P. Gonzalez L. Calvet X. Systematic review and meta-analysis: PPI vs. ranitidine bismuth citrate plus two antibiotics in Helicobacter pylori eradication.Helicobacter. 2005; 10: 157-171Crossref PubMed Scopus (48) Google Scholar It is a reasonable alternative in areas in which it remains available.The penicillin allergic patientBismuth quadruple therapy is a reasonable alternative to standard PPI triple therapy when penicillin allergy is present. In regions in which ranitidine bismuth citrate is available, a combination of ranitidine bismuth citrate with tetracycline and metronidazole has been used.28Gisbert J.P. Gisbert J.L. Marcos S. et al.Helicobacter pylori first-line treatment and rescue options in patients allergic to penicillin.Aliment Pharmacol Ther. 2005; 22: 1041-1046Crossref PubMed Scopus (32) Google Scholar A combination of a PPI with metronidazole and clarithromycin has also been used but has a lower eradication rate (77%).17Bochenek W.J. Peters S. Fraga P.D. et al.Helicobacter pylori Pantoprazole Eradication (HELPPE) Study GroupEradication of Helicobacter pylori by 7-day triple-therapy regimens combining pantoprazole with clarithromycin, metronidazole, or amoxicillin in patients with peptic ulcer disease: results of two double-blind, randomized studies.Helicobacter. 2003; 8: 626-642Crossref PubMed Scopus (45) Google ScholarSequential therapy for H pylori eradicationSequential therapy is a major new innovation in the treatment of H pylori. The sequential regimen is a 10-day treatment consisting of a PPI and amoxycillin 1 g (both twice daily) administered for the first 5 days followed by triple therapy consisting of a PPI, clarithromycin 500 mg, and tinidazole 500 mg (all twice daily) for the remaining 5 days. The idea was born of earlier observations made when 2-drug therapies (PPI + amoxicillin) were in use. It was observed that the eradication rate achieved with a therapeutic strategy of initially administering 14-day dual therapy (PPI + amoxicillin) followed by 7-day triple therapy in individuals who failed the original therapy was significantly better than the reverse sequence (7-day triple therapy as an initial strategy with 14-day dual therapy for failures).29Rinaldi V. Zullo A. Pugliano F. et al.The management of failed dual or triple therapy for Helicobacter pylori eradication.Aliment Pharmacol Ther. 1997; 11: 929-933Crossref PubMed Google Scholar A series of studies performed in Italy have shown excellent results with sequential therapy, and, if these results are confirmed in other parts of the world, it is likely that we may be looking at eradication therapy in a new light, considering sequences of medications rather than complex regimens of individual drugs. Six published Italian trials that each involve more than 100 patients are presented in Table 2.30Zullo A. Vaira D. Vakil N. et al.High eradication rates of Helicobacter pylori with a new sequential treatment.Aliment Pharmacol Ther. 2003; 17: 719-726Crossref PubMed Scopus (183) Google Scholar, 31Hassan C. De Francesco V. Zullo A. et al.Sequential treatment for Helicobacter pylori eradication in duodenal ulcer patients: improving the cost of pharmacotherapy.Aliment Pharmacol Ther. 2003; 18: 641-646Crossref PubMed Scopus (41) Google Scholar, 32Focareta R. Forte G. Forte F. et al.Could the 10-days sequential therapy be considered a first choice treatment for the eradication of Helicobacter pylori infection?.Dig Liver Dis. 2003; 35: S33Google Scholar, 33De Francesco V. Della Valle N. Stoppino V. et al.Effectiveness and pharmaceutical cost of sequential treatment for Helicobacter pylori in patients with non-ulcer dyspepsia.Aliment Pharmacol Ther. 2004; 19: 993-998Crossref PubMed Scopus (33) Google Scholar, 34De Francesco V. Zullo A. Hassan C. et al.The prolongation of triple therapy for Helicobacter pylori does not allow reaching therapeutic outcome of sequential scheme: a prospective, randomized study.Dig Liver Dis. 2004; 36: 322-326Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 35Vaira D. Zullo A. Vakil N. et al.Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial.Ann Intern Med. 2007; 146: 556-563Crossref PubMed Google Scholar The eradication rate was uniformly above 90% (Table 2). A recent Spanish study, still in preliminary form, provides evidence from another country of the merit of this regimen.36Delgado J. Bujanda L. Gisbert P. et al.Effectiveness of a 10-day sequential treatment for Helicobacter pylori eradication in clinical practice.Gastroenterology. 2007; 132 (abstr): A–112Google Scholar The precise mechanism for the success of the sequential therapy is not known. One possibility is that decreasing the bacterial density in the stomach with a drug such as amoxicillin (to which resistance is rare) improves the efficacy of the subsequently administered combination of clarithromycin and tinidazole. It is known that bacteria can develop efflux channels for clarithromycin, which rapidly transfer the drug out of the bacterial cell, preventing binding of the antibiotic to the ribosome.37De Francesco V. Margiotta M. Zullo A. et al.Clarithromycin-resistant genotypes and eradication of Helicobacter pylori.Ann Intern Med. 2006; 144: 94-100Crossref PubMed Google Scholar Because amoxicillin acts on the bacterial cell wall and weakens it, the initial phase of treatment may prevent the development of efflux channels by weakening the cell wall of the bacterium.Table 2Sequential Therapy: Trials With More Than 100 Patients Given Sequential TherapyAuthor (reference)YearNo. of centersPatients enrolledEradication rate (%)95% CIZullo et al30Zullo A. Vaira D. Vakil N. et al.High eradication rates of Helicobacter pylori with a new sequential treatment.Aliment Pharmacol Ther. 2003; 17: 719-726Crossref PubMed Scopus (183) Google Scholar200385229289.8–93.7Hassan et al31Hassan C. De Francesco V. Zullo A. et" @default.
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• W1966243555 title "Eradication Therapy for Helicobacter pylori" @default.
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