Skip to main content
SpringerLink
Log in

Efficacy and Safety of Quinolone-Containing Rescue Therapies After the Failure of Non-Bismuth Quadruple Treatments for Helicobacter pylori Eradication: Systematic Review and Meta-Analysis

  • Systematic Review
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Background

Anti-Helicobacter pylori eradication treatment fails in a significant percentage of cases. Although this percentage has been reduced to 5–15% with the use of non-bismuth quadruple therapies, limited data exist regarding rescue after failure of these treatments.

Aim

The aim of this study was to systematically review the efficacy and safety of quinolone-containing therapies after the failure of non-bismuth quadruple regimens.

Methods

Studies evaluating the efficacy of second-line quinolone-containing therapies after the failure of non-bismuth sequential or concomitant regimens were selected. Efficacy (by intention to treat) was analyzed using the inverse variance method; safety data were recorded as the occurrence of any adverse event. The risk of bias of each primary study was evaluated using the Risk of Bias in Non-randomized Studies—of Interventions (ROBINS-I) tool. The quality of the evidence was summarized using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach.

Results

Sixteen studies were included. The 10-day levofloxacin/amoxicillin/proton pump inhibitor (PPI) triple therapy (LT) achieved eradication rates of 80% (95% CI 71–88). Regarding the moxifloxacin/amoxicillin/PPI triple therapy (MT), its efficacy was higher when administered for 14 days instead of 7 days (80 vs 63%). Two studies investigated the levofloxacin/bismuth-containing quadruple therapies (LBQ) obtaining eradication rates over 90%. Safety was similar in all treatments. The sensitivity analyses showed that results for LT were robust, but MT had weak evidence.

Conclusions

Quinolone-containing triple therapies reported eradication rates ≤80%, but LBQ therapies showed encouraging rates. However, the strength of the evidence was very low. The efficacy of LBQ should be corroborated in more studies, and the usefulness of quinolones needs to be evaluated in areas with moderate to high bacterial resistances.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Malfertheiner P, Megraud F, O’Morain CA, Gisbert JP, Kuipers EJ, Axon AT, et al. Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report. Gut. 2016;. doi:10.1136/gutjnl-2016-312288.

    PubMed Central  Google Scholar 

  2. Fallone CA, Chiba N, van Zanten SV, Fischbach L, Gisbert JP, Hunt RH, et al. The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology 2016;151(1):51–69 e14. doi:10.1053/j.gastro.2016.04.006.

  3. Gisbert JP, Molina-Infante J, Amador J, Bermejo F, Bujanda L, Calvet X, et al. IV Spanish consensus conference on Helicobacter pylori infection treatment. Gastroenterol Hepatol. 2016. doi:10.1016/j.gastrohep.2016.05.003.

  4. Gisbert JP, Calvet X. Review article: the effectiveness of standard triple therapy for Helicobacter pylori has not changed over the last decade, but it is not good enough. Aliment Pharmacol Ther. 2011;34(11–12):1255–68. doi:10.1111/j.1365-2036.2011.04887.x.

    Article  CAS  PubMed  Google Scholar 

  5. Chey WD, Wong BC. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102(8):1808–25. doi:10.1111/j.1572-0241.2007.01393.x.

    Article  CAS  PubMed  Google Scholar 

  6. Kim JS, Park SM, Kim BW. Sequential or concomitant therapy for eradication of Helicobacter pylori infection: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2015;30(9):1338–45. doi:10.1111/jgh.12984.

    Article  CAS  PubMed  Google Scholar 

  7. Nyssen OP, McNicholl AG, Megraud F, Savarino V, Oderda G, Fallone CA, et al. Sequential versus standard triple first-line therapy for Helicobacter pylori eradication. Cochrane Database Syst Rev. 2016(6):CD009034. doi:10.1002/14651858.CD009034.pub2.

  8. Gatta L, Vakil N, Leandro G, Di Mario F, Vaira D. Sequential therapy or triple therapy for Helicobacter pylori infection: systematic review and meta-analysis of randomized controlled trials in adults and children. Am J Gastroenterol. 2009;104(12):3069–79. doi:10.1038/ajg.2009.555. (quiz 1080)

  9. Song ZQ, Zhou LY. Hybrid, sequential and concomitant therapies for Helicobacter pylori eradication: a systematic review and meta-analysis. World J Gastroenterol. 2016;22(19):4766–75. doi:10.3748/wjg.v22.i19.4766.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Gisbert JP, Calvet X. Review article: non-bismuth quadruple (concomitant) therapy for eradication of Helicobater pylori. Aliment Pharmacol Ther. 2011;34(6):604–17. doi:10.1111/j.1365-2036.2011.04770.x.

    Article  CAS  PubMed  Google Scholar 

  11. Megraud F. H pylori antibiotic resistance: prevalence, importance, and advances in testing. Gut. 2004;53(9):1374–84. doi:10.1136/gut.2003.022111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Forman D, Graham DY. Review article: impact of Helicobacter pylori on society-role for a strategy of ‘search and eradicate’. Aliment Pharmacol Ther. 2004;19(Suppl 1):17–21.

    Article  PubMed  Google Scholar 

  13. Gisbert JP. “Rescue” regimens after Helicobacter pylori treatment failure. World J Gastroenterol. 2008;14(35):5385–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. 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(5):646–64. doi:10.1136/gutjnl-2012-302084.

    Article  CAS  PubMed  Google Scholar 

  15. Gisbert JP, Pajares JM. Review article: Helicobacter pylori “rescue” regimen when proton pump inhibitor-based triple therapies fail. Aliment Pharmacol Ther. 2002;16(6):1047–57.

    Article  CAS  PubMed  Google Scholar 

  16. Chen PY, Wu MS, Chen CY, Bair MJ, Chou CK, Lin JT, et al. Systematic review with meta-analysis: the efficacy of levofloxacin triple therapy as the first- or second-line treatments of Helicobacter pylori infection. Aliment Pharmacol Ther. 2016;44(5):427–37. doi:10.1111/apt.13712.

    Article  CAS  PubMed  Google Scholar 

  17. 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(3):562–7.

    Article  CAS  PubMed  Google Scholar 

  18. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. doi:10.1371/journal.pmed.1000097.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Review Manager (RevMan) (computer program). Version 5.3. Copenhagen: The Nordic Cochrane Centre TCC, 2014.

  20. Sterne JA, Hernan MA, Reeves BC, Savovic J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. doi:10.1136/bmj.i4919.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Guyatt GH, Oxman AD, Schunemann HJ, Tugwell P, Knottnerus A. GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. J Clin Epidemiol. 2011;64(4):380–2. doi:10.1016/j.jclinepi.2010.09.011.

    Article  PubMed  Google Scholar 

  22. Gisbert JP, Molina-Infante J, Marin AC, Rodriguez GV, Barrio J, McNicholl AG. Second-line rescue triple therapy with levofloxacin after failure of non-bismuth quadruple “sequential” or “concomitant” treatment to eradicate H. pylori infection. Gastroenterology 2014;146(5 suppl. 1):S-394.

  23. Gisbert JP, Molina-Infante J, Marin AC, Vinagre G, Barrio J, McNicholl AG. Second-line rescue triple therapy with levofloxacin after failure of non-bismuth quadruple “sequential” or “concomitant” treatment to eradicate H. pylori infection. Scand J Gastroenterol. 2013;48(6):652–6. doi:10.3109/00365521.2013.786132.

    Article  CAS  PubMed  Google Scholar 

  24. Hsu PI, Chen WC, Tsay FW, Shih CA, Kao SS, Wang HM, et al. Ten-day quadruple therapy comprising proton-pump inhibitor, bismuth, tetracycline, and levofloxacin achieves a high eradication rate for Helicobacter pylori infection after failure of sequential therapy. Helicobacter. 2014;19(1):74–9. doi:10.1111/hel.12085.

    Article  CAS  PubMed  Google Scholar 

  25. Chung KH, Lee DH, Jin E, Cho Y, Seo JY, Kim N, et al. The efficacy of moxifloxacin-containing triple therapy after standard triple, sequential, or concomitant therapy failure for Helicobacter pylori eradication in Korea. Gut Liver. 2014;8(6):605–11. doi:10.5009/gnl13303.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kang KK, Lee DH, Oh DH, Yoon H, Shin CM, Park YS, et al. Helicobacter pylori eradication with moxifloxacin-containing therapy following failed first-line therapies in South Korea. World J Gastroenterol. 2014;20(22):6932–8. doi:10.3748/wjg.v20.i22.6932.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Lim JH, Lee DH, Lee ST, Kim N, Park YS, Shin CM, et al. Moxifloxacin-containing triple therapy after non-bismuth quadruple therapy failure for Helicobacter pylori infection. World J Gastroenterol. 2015;21(46):13124–31. doi:10.3748/wjg.v21.i46.13124.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Campillo A, Amorena E, Ostiz M. Local experience with non-bismuth quadruple therapy as first line treatment for helicobacter pylori eradication. United Eur Gastroenterol J. 2013;1(1 Suppl. 1):A271.

    Google Scholar 

  29. Cerqueira R, Correia M, Vilar H, Conceicao Manso M. Cumulative Helicobacter pylori eradication therapy in obese patients undergoing gastric bypass surgery. United Eur Gastroenterol J. 2015;3(5 suppl. 1):A496.

  30. Georgopoulos SD, Xirouchakis E, Martinez-Gonzalez B, Sgouras DN, Spiliadi C, Mentis AF, et al. Clinical evaluation of a ten-day regimen with esomeprazole, metronidazole, amoxicillin, and clarithromycin for the eradication of Helicobacter pylori in a high clarithromycin resistance area. Helicobacter. 2013;18(6):459–67. doi:10.1111/hel.12062.

    Article  CAS  PubMed  Google Scholar 

  31. Zullo A, Scaccianoce G, De Francesco V, Ruggiero V, D’Ambrosio P, Castorani L, et al. Concomitant, sequential, and hybrid therapy for H. pylori eradication: a pilot study. Clin Res Hepatol Gastroenterol. 2013;37(6):647–50. doi:10.1016/j.clinre.2013.04.003.

  32. Zullo A, de Francesco V, Panella C, Morini S, Ierardi E. Second-line treatment for Helicobacter pylori eradication after sequential therapy failure: a pilot study. Therapy. 2006;3(2):251–4.

    Article  CAS  Google Scholar 

  33. Manfredi M, Bizzarri B, de’Angelis GL. Helicobacter pylori infection: sequential therapy followed by levofloxacin-containing triple therapy provides a good cumulative eradication rate. Helicobacter 2012;17(4):246–53. doi:10.1111/j.1523-5378.2012.00945.x.

  34. Perna F, Zullo A, Ricci C, Hassan C, Morini S, Vaira D. Levofloxacin-based triple therapy for Helicobacter pylori re-treatment: role of bacterial resistance. Dig Liver Dis. 2007;39(11):1001–5. doi:10.1016/j.dld.2007.06.016.

    Article  CAS  PubMed  Google Scholar 

  35. Pontone S, Standoli M, Angelini R, Pontone P. Efficacy of H. pylori eradication with a sequential regimen followed by rescue therapy in clinical practice. Dig Liver Dis. 2010;42(8):541–3. doi:10.1016/j.dld.2009.12.007.

    Article  PubMed  Google Scholar 

  36. Gisbert JP, Romano M, Molina-Infante J, Lucendo AJ, Medina E, Modolell I, et al. Two-week, high-dose proton pump inhibitor, moxifloxacin triple Helicobacter pylori therapy after failure of standard triple or non-bismuth quadruple treatments. Dig Liver Dis. 2015;47(2):108–13. doi:10.1016/j.dld.2014.10.009.

    Article  CAS  PubMed  Google Scholar 

  37. Gisbert JP, Romano M, Gravina AG, Solis-Munoz P, Bermejo F, Molina-Infante J, et al. Helicobacter pylori second-line rescue therapy with levofloxacin- and bismuth-containing quadruple therapy, after failure of standard triple or non-bismuth quadruple treatments. Aliment Pharmacol Ther. 2015;41(8):768–75. doi:10.1111/apt.13128.

    Article  CAS  PubMed  Google Scholar 

  38. Song Z, Zhou L, Zhang J, He L, Bai P, Xue Y. Levofloxacin, bismuth, amoxicillin and esomeprazole as second-line Helicobacter pylori therapy after failure of non-bismuth quadruple therapy. Dig Liver Dis. 2016;48(5):506–11. doi:10.1016/j.dld.2016.01.002.

    Article  CAS  PubMed  Google Scholar 

  39. Liou JM, Chen CC, Chen MJ, Chang CY, Fang YJ, Lee JY, et al. Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet. 2013;381(9862):205–13. doi:10.1016/S0140-6736(12)61579-7.

    Article  PubMed  Google Scholar 

  40. Marin AC, McNicholl AG, Gisbert JP. A review of rescue regimens after clarithromycin-containing triple therapy failure (for Helicobacter pylori eradication). Expert Opin Pharmacother. 2013;14(7):843–61. doi:10.1517/14656566.2013.782286.

    Article  CAS  PubMed  Google Scholar 

  41. Malfertheiner P. Infection: bismuth improves PPI-based triple therapy for H. pylori eradication. Nat Rev Gastroenterol Hepatol. 2010;7(10):538–9. doi:10.1038/nrgastro.2010.131.

    Article  CAS  PubMed  Google Scholar 

  42. Liao J, Zheng Q, Liang X, Zhang W, Sun Q, Liu W, et al. Effect of fluoroquinolone resistance on 14-day levofloxacin triple and triple plus bismuth quadruple therapy. Helicobacter. 2013;18(5):373–7. doi:10.1111/hel.12052.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author contributions

JPG and AGM proposed the research question. ACM and AGM designed the protocol of the systematic review. ACM and OPN performed in duplicate the selection of the studies, extracted the efficacy and safety data for the meta-analysis, evaluated the risk of bias of the individual studies, and summarized the quality of the evidence using GRADE; if discordances were found, consensus was reached with a third reviewer (AGM). ACM wrote the first draft with the assistance of OPN. All the authors reviewed the numerical data and collaborated in the statistical analyses and in the writing of the final manuscript.

Author information

Authors and Affiliations

  1. Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain

    Alicia C. Marin, Olga P. Nyssen, Adrian G. McNicholl & Javier P. Gisbert

  2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain

    Alicia C. Marin, Olga P. Nyssen, Adrian G. McNicholl & Javier P. Gisbert

Authors
  1. Alicia C. Marin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Olga P. Nyssen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adrian G. McNicholl
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Javier P. Gisbert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adrian G. McNicholl.

Ethics declarations

Conflicts of interest

JP Gisbert has served as speaker, consultant and advisory member for or has received research funding from Almirall, Nycomed, AstraZeneca, Casen Recordati, and Allergan. AG McNicholl has served as a speaker for Allergan. AC Marin and OP Nyssen have no conflicts of interest.

Funding

No external funding sources were used in the preparation of this manuscript.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Marin, A.C., Nyssen, O.P., McNicholl, A.G. et al. Efficacy and Safety of Quinolone-Containing Rescue Therapies After the Failure of Non-Bismuth Quadruple Treatments for Helicobacter pylori Eradication: Systematic Review and Meta-Analysis. Drugs 77, 765–776 (2017). https://doi.org/10.1007/s40265-017-0730-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-017-0730-4

Keywords

Search

Navigation