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Does emerging Clarithromycin resistance signal an obituary to empirical standard triple therapy for Helicobacter pylori infection?

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Abstract

Despite 30 years of its discovery, the ideal therapeutic regimen against Helicobacter pylori is still evasive. Clarithromycin-based standard triple therapy which has been considered the first line empirical therapy has been failing in many parts of the world, due to rising resistance against Clarithromycin, forcing the use of alternate regimens. In this context, we studied the local antibiotic resistance patterns against H. pylori and its impact on standard triple therapy in our region. All patients undergoing diagnostic upper endoscopy during the study period and detected to be positive for rapid urease test (RUT) underwent cultures of gastric mucosal specimens and had their antibiotic resistance patterns mapped out. Standard triple therapy was administered to those tested positive for H. pylori by RUT and eradication rates checked by urea breath test 4 weeks after the completion of treatment. Eradication rates with Clarithromycin-based standard triple therapy were suboptimal with a success of only (71.28 %). H. pylori culture and antibiotic susceptibility studies showed high resistance to Clarithromycin (21.2 %), Metronidazole (78.1 %), and Levofloxacin (15 %). However, the resistance to Amoxicillin (2.9 %), Tetracycline (0 %), and Rifabutin (4.5 %) were low. Standard triple therapy is failing in our region due to high Clarithromycin resistance. We need to abandon empirical and blind triple therapy without post-treatment testing and devise alternate effective treatment strategies against H. pylori based on the local resistance patterns observed.

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References

  1. Malfertheiner P, Mégraud F, O’Morain C, et al. Current European concepts in the management of Helicobacter pylori infection—the Maastricht Consensus Report. The European Helicobacter Pylori Study Group (EHPSG). Eur J Gastroenterol Hepatol. 1997;9:1–2.

    Article  CAS  PubMed  Google Scholar 

  2. Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pylori infection—the Maastricht IV/ Florence Consensus Report. Gut. 2012;61:646–64.

    Article  CAS  PubMed  Google Scholar 

  3. Fischbach LA, Goodman KJ, Feldman M, Aragaki C. Sources of variation of Helicobacter pylori treatment success in adults worldwide: a meta-analysis. Int J Epidemiol. 2002;31:128–39.

    Article  PubMed  Google Scholar 

  4. Song M, Ang TL. Second and third line treatment options for Helicobacter pylori eradication. World J Gastroenterol. 2014;20:1517–28.

  5. Ierardi E, Giorgio F, Losurdo G, Di Leo A, Principi M. How antibiotic resistances could change helicobacter pylori treatment: a matter of geography? World J Gastroenterol. 2013;19:8168–80.

  6. Megraud F, Lehours P. Helicobacter pylori detection and antimicrobial susceptibility testing. Clin Microbiol Rev. 2007;20:280–322.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Cederbrant G, Kahlmeter G, Ljungh A. The E test for antimicrobial susceptibility testing of Helicobacter pylori. J Antimicrob Chemother. 1993;31:65–71.

    Article  CAS  PubMed  Google Scholar 

  8. Wueppenhorst N, Stueger HP, Kist M, Glocker E. Identification and molecular characterization of triple- and quadruple-resistant Helicobacter pylori clinical isolates in Germany. J Antimicrob Chemother. 2009;63:648–53.

    Article  CAS  PubMed  Google Scholar 

  9. De Francesco V, Giorgio F, Hassan C, et al. Worldwide H. pylori antibiotic resistance: a systematic review. J Gastrointestin Liver Dis. 2010;19:409–14.

    PubMed  Google Scholar 

  10. Horiki N, Omata F, Uemura M, et al. Annual change of primary resistance to clarithromycin among Helicobacter pylori isolates from 1996 through 2008 in Japan. Helicobacter. 2009;14:86–90.

    Article  CAS  PubMed  Google Scholar 

  11. Fischbach L, Evans EL. Meta-analysis: the effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapies for Helicobacter pylori. Aliment Pharmacol Ther. 2007;26:343–57.

    Article  CAS  PubMed  Google Scholar 

  12. Occhialini A, Urdaci M, Doucet-Populaire F, Bébéar CM, Lamouliatte H, Mégraud F. Macrolide resistance in Helicobacter pylori: rapid detection of point mutations and assays of macrolide binding to ribosomes. Antimicrob Agents Chemother. 1997;41:2724–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  13. Megraud F, Coenen S, Versporten A, et al. Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut. 2013;62:34–42.

    Article  CAS  PubMed  Google Scholar 

  14. De Francesco V, Margiotta M, Zullo A, et al. Claritromycin resistance and Helicobacter pylori genotypes in Italy. J Microbiol. 2006;44:660–4.

    PubMed  Google Scholar 

  15. Liou JM, Chen CC, Chen MJ, et al. Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet. 2013;381:205–13.

    Article  PubMed  Google Scholar 

  16. Gisbert JP, Calvet X, O’Connor A, Mégraud F, O’Morain CA. Sequential therapy for Helicobacter pylori eradication: a critical review. J Clin Gastroenterol. 2010;44:313–25.

  17. Yoon H, Lee DH, Kim N, et al. Meta-analysis: is sequential therapy superior to standard triple therapy for Helicobacter pylori infection in Asian adults? J Gastroenterol Hepatol. 2013;28:1801–9.

    Article  PubMed  Google Scholar 

  18. Essa AS, Kramer JR, Graham DY, Treiber G. Meta-analysis: four-drug, three-antibiotic, non-bismuth-containing ‘concomitant therapy’ versus triple therapy for helicobacter pylori eradication. Helicobacter. 2009;14:109–18.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Federico A, Nardone G, Gravina AG, et al. Efficacy of 5-day levofloxacin-containing concomitant therapy in eradication of Helicobacter pylori infection. Gastroenterology. 2012;143:55–61.

    Article  CAS  PubMed  Google Scholar 

  20. Malfertheiner P, Bazzoli F, Delchier JC, 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;377:905–13.

    Article  CAS  PubMed  Google Scholar 

  21. Liang X, Xu X, Zheng Q, et al. Efficacy of bismuth-containing quadruple therapies for clarithromycin-, metronidazole-, and fluoroquinolone-resistant Helicobacter pylori infections in a prospective study. Clin Gastroenterol Hepatol. 2013;11:802–7.

    Article  CAS  PubMed  Google Scholar 

  22. Hsu PI, Chen WC, Tsay FW, 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 therap. Helicobacter. 2014;19:74–9.

    Article  CAS  PubMed  Google Scholar 

  23. Liu KS, Hung IF, Seto WK, et al. Ten day sequential versus 10 day modified bismuth quadruple therapy as empirical firstline and second linetreatment for Helicobacter pylori in Chinese patients: an open label, randomised, crossover trial. Gut. 2014;63:1410–5.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to acknowledge the financial support provided by the Medical Research Center, Hamad Medical Corporation, Doha, Qatar, and also the services of Mr. Noufal K who served as coordinator. We also place on record our appreciation of the services of Ms. Cosima Langner, GI Research Laboratory, Otto-Von-Guericke University, Magdeburg, Germany, for performing the H. pylori cultures.

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Authors and Affiliations

  1. Department of Gastroenterology, Hamad Medical Corporation, Doha, Qatar

    Anil John, Saad Al Kaabi, Manik Sharma, Ragesh Babu, Rafie Yacoub & Moutaz Derbala

  2. Department of Microbiology, Hamad Medical Corporation, Doha, Qatar

    Sanjay Doiphode

  3. Department of Medical Research, Hamad Medical Corporation, Doha, Qatar

    Prem Chandra

Authors
  1. Anil John
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  2. Saad Al Kaabi
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  3. Sanjay Doiphode
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  4. Prem Chandra
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  5. Manik Sharma
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  6. Ragesh Babu
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  7. Rafie Yacoub
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  8. Moutaz Derbala
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Corresponding author

Correspondence to Anil John.

Ethics declarations

The study was performed in a manner to conform with the Helsinki Declaration of 1975, as revised in 2000 and 2008, concerning Human and Animal Rights, and the authors followed the policy concerning informed consent as shown on Springer.com.

Conflict of interest

AJ, SAK, SD, PC, MS, RB, RY, and MD declare that they have no competing interests.

Funding

This research was conducted with funding provided by the Medical Research Center, Hamad Medical Corporation, Doha, Qatar through research proposal number 12014/12.

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John, A., Al Kaabi, S., Doiphode, S. et al. Does emerging Clarithromycin resistance signal an obituary to empirical standard triple therapy for Helicobacter pylori infection?. Indian J Gastroenterol 34, 404–407 (2015). https://doi.org/10.1007/s12664-015-0604-1

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  • DOI: https://doi.org/10.1007/s12664-015-0604-1

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