Abstract
Background: In areas with high clarithromycin resistance, bismuth quadruple therapy (BQT) is recommended instead of clarithromycin triple therapy (CTT) as the first-line treatment for Helicobacter pylori eradication. Methods: Randomized clinical trials (RCTs) comparing BQT to CTT were identified through electronic and manual searches. A meta-analysis was performed to compare the efficacy and tolerability of these two regimens as first-line treatments for H. pylori infection. The effect of antibiotic resistance on treatment efficacy was also analyzed. Results: Twelve RCTs were included. BQT achieved eradication in 77.6% of patients, whereas CTT achieved an eradication rate of 68.9% [risk difference (RD) = 0.06, 95% CI: -0.01/0.13]. A high heterogeneity among the trials was found (χ2 = 50.16, p < 0.00001; I2 = 78%). In the subgroup analysis for treatment duration, the 10-day BQT was more effective than the 7-day CTT (RD = 0.25, 95% CI: 0.18/0.32), whereas no differences were observed between CTT and BQT given for 7 or 10 days. There were no statistical differences in side effects and compliance between both therapies (RD = 0.92, 95% CI: 0.76/1.12, and RD = -0.03, 95% CI: -0.05/0.00, respectively). The effect of antibiotic resistance on eradication rates was reported in 4 of the 12 RCTs. Clarithromycin resistance significantly affected the efficacy of CTT (RD = 0.75, 95% CI: 0.63/0.87), whereas BQT efficacy was not affected by metronidazole resistance (RD = 0.09, 95% CI: -0.06/0.25). Conclusions: The 10-day BQT was more effective than the 7-day CTT as a first-line therapy for H. pylori infection, whereas BQT and CTT for 7 or 10 days yielded similar eradication rates. Compliance and side effect rates were similar for both therapies. BQT overcomes clarithromycin resistance and its efficacy is not affected by metronidazole resistance.
Journal Section:
Review
References
1.
Nagini S: Carcinoma of the stomach: a review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol 2012;4:156-169.
[PubMed]
2.
Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, et al: Management of Helicobacter pylori infection - the Maastricht IV/Florence Consensus Report. Gut 2012;61:646-664.
[PubMed]
3.
Glupczynski Y, Megraud F, Lopez-Brea M, Andersen LP: European multicentre survey of in vitro antimicrobial resistance in Helicobacter pylori. Eur J Clin Microbiol Infect Dis 2001;20:820-823.
[PubMed]
4.
Megraud F, Coenen S, Versporten A, Kist M, Lopez-Brea M, Hirschl AM, et al: Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut 2013;62:34-42.
[PubMed]
5.
Gene E, Calvet X, Azagra R, Gisbert JP: Triple vs. quadruple therapy for treating Helicobacter pylori infection: a meta-analysis. Aliment Pharmacol Ther 2003;17:1137-1143.
[PubMed]
6.
Luther J, Higgins PD, Schoenfeld PS, Moayyedi P, Vakil N, Chey WD: Empiric quadruple vs. triple therapy for primary treatment of Helicobacter pylori infection: systematic review and meta-analysis of efficacy and tolerability. Am J Gastroenterol 2010;105:65-73.
[PubMed]
7.
Leandro G: Meta-Analysis in Medical Research: The Handbook for the Understanding and Practice of Meta-Analysis (with software). Malden, BMJ Books, 2005.
8.
Gomollon F, Valdeperez J, Garuz R, Fuentes J, Barrera F, Malo J, et al: Cost-effectiveness analysis of 2 strategies of Helicobacter pylori eradication: results of a prospective and randomized study in primary care. Medicina Clinica 2000;115:1-6.
[PubMed]
9.
Calvet X, Ducons J, Guardiola J, Tito L, Andreu V, Bory F, et al: One-week triple vs. quadruple therapy for Helicobacter pylori infection - a randomized trial. Aliment Pharmacol Ther 2002;16:1261-1267.
[PubMed]
10.
Katelaris PH, Forbes GM, Talley NJ, Crotty B: A randomized comparison of quadruple and triple therapies for Helicobacter pylori eradication: The QUADRATE Study. Gastroenterology 2002;123:1763-1769.
[PubMed]
11.
Mantzaris GJ, Petraki K, Archavlis E, Amberiadis P, Christoforidis P, Kourtessas D, et al: Omeprazole triple therapy versus omeprazole quadruple therapy for healing duodenal ulcer and eradication of Helicobacter pylori infection: a 24-month follow-up study. Eur J Gastroenterol Hepatol 2002;14:1237-1243.
[PubMed]
12.
Laine L, Hunt R, El-Zimaity H, Nguyen B, Osato M, Spenard J: 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;98:562-567.
[PubMed]
13.
Pai CG, Thomas CP, Biswas A, Rao S, Ramnarayan K: Quadruple therapy for initial eradication of Helicobacter pylori in peptic ulcer: comparison with triple therapy. Indian J Gastroenterol 2003;22:85-87.
[PubMed]
14.
Jang HJ, Choi MH, Kim YS, Seo YA, Baik KH, Baik IH, et al: Effectiveness of triple therapy and quadruple therapy for Helicobacter pylori eradication (in Korean). Korean J Gastroenterol 2005;46:368-372.
[PubMed]
15.
Uygun A, Kadayifci A, Safali M, Ilgan S, Bagci S: The efficacy of bismuth containing quadruple therapy as a first-line treatment option for Helicobacter pylori. J Dig Dis 2007;8:211-215.
[PubMed]
16.
Ching SS, Sabanathan S, Jenkinson LR: Treatment of Helicobacter pylori in surgical practice: a randomised trial of triple versus quadruple therapy in a rural district general hospital. World J Gastroenterol 2008;14:3855-3860.
[PubMed]
17.
Songür Y, Senol A, Balkarli A, Basturk A, Cerci S: Triple or quadruple tetracycline-based therapies versus standard triple treatment for Helicobacter pylori treatment. Am J Med Sci 2009;338:50-53.
[PubMed]
18.
Zheng Q, Chen WJ, Lu H, Sun QJ, Xiao SD: Comparison of the efficacy of triple versus quadruple therapy on the eradication of Helicobacter pylori and antibiotic resistance. J Dig Dis 2010;11:313-318.
[PubMed]
19.
Malfertheiner P, Bazzoli F, Delchier JC, Celinski K, Giguere M, Riviere M, et al: 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. Lancet 2011;377:905-913.
[PubMed]
20.
Singh V, Mishra S, Maurya P, Rao G, Jain AK, Dixit VK, et al: Drug resistance pattern and clonality in H. pylori strains. J Infect Dev Ctries, 2009;3:130-136.
[PubMed]
21.
Chung JW, Lee GH, Jeong JY, Lee SM, Jung JH, Choi KD, et al: Resistance of Helicobacter pylori strains to antibiotics in Korea with a focus on fluoroquinolone resistance. J Gastroenterol Hepatol 2012;27:493-497.
[PubMed]
22.
Onder G, Aydin A, Akarca U, Tekin F, Ozutemiz O, Ilter T: High Helicobacter pylori resistance rate to clarithromycin in Turkey. J Clin Gastroenterol 2007;41:747-750.
[PubMed]
23.
Fuccio L, Minardi ME, Zagari RM, Grilli D, Magrini N, Bazzoli F: Meta-analysis: duration of first-line proton-pump inhibitor based triple therapy for Helicobacter pylori eradication. Ann Intern Med 2007;147:553-562.
[PubMed]
24.
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al: Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1-12.
[PubMed]
25.
Zagari RM, Bianchi-Porro G, Fiocca R, Gasbarrini G, Roda E, Bazzoli F: Comparison of 1 and 2 weeks of omeprazole, amoxicillin and clarithromycin treatment for Helicobacter pylori eradication: the HYPER Study. Gut 2007;56:475-479.
[PubMed]
26.
Rimbara E, Fischbach LA, Graham DY: Optimal therapy for Helicobacter pylori infections. Nat Rev Gastroenterol Hepatol 2011;8:79-88.
[PubMed]
27.
Chey WD, Wong BC: American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol 2007;102:1808-1825.
[PubMed]
28.
Fock KM, Katelaris P, Sugano K, Ang TL, Hunt R, Talley NJ, et al: Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection. J Gastroenterol Hepatol 2009;24:1587-1600.
[PubMed]
29.
Asaka M, Kato M, Takahashi S, Fukuda Y, Sugiyama T, Ota H, et al: Guidelines for the management of Helicobacter pylori infection in Japan: 2009 revised edition. Helicobacter 2010;15:1-20.
[PubMed]
30.
de Boer WA: Bismuth triple therapy: still a very important drug regimen for curing Helicobacter pylori infection. Eur J Gastroenterol Hepatol 1999;11:697-700.
[PubMed]
31.
van der Wouden EJ, Thijs JC, van Zwet AA, Sluiter WJ, Kleibeuker JH: The influence of in vitro nitroimidazole resistance on the efficacy of nitroimidazole-containing anti-Helicobacter pylori regimens: a meta-analysis. Am J Gastroenterol 1999;94:1751-1759.
[PubMed]
32.
Graham DY, Fischbach L: Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut 2010;59:1143-1153.
[PubMed]
33.
Megraud F, Broutet N: Epidemiologie des maladies infectieuses en France en 1997. Surveillance de la resistance aux antibiotiques. Bull Epidemiol Ann 1999:187-188.
34.
Salazar CO, Cardenas VM, Reddy RK, Dominguez DC, Snyder LK, Graham DY: Greater than 95% success with 14-day bismuth quadruple anti-Helicobacter pylori therapy: a pilot study in US Hispanics. Helicobacter 2012;17:382-390.
[PubMed]
© 2013 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2013
You do not currently have access to this content.
