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Helicobacter pylori Clarithromycin Resistance and Treatment Failure Are Common in the USA

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Abstract

Background

Helicobacter pylori antibiotic resistance leads to frequent treatment failure. However, the current US prevalence of H. pylori clarithromycin resistance and treatment failure is unknown.

Aims

To determine the prevalence of clarithromycin-resistant H. pylori and its impact on treatment failure in the USA.

Methods

A multicenter, retrospective, cohort study for clarithromycin-resistant H. pylori was conducted over four academic medical centers in different geographic regions of the USA. Gastric biopsy material, residual from standard clinical pathologic examination, was examined for clarithromycin resistance by DNA sequencing of H. pylori 23S rRNA.

Results

One hundred and twenty-four cases of H. pylori gastritis were examined from medical centers in four different geographic regions of the USA. The overall prevalence of clarithromycin resistance was 32.3 % (range 23.1–45.8 %). There was no significant difference in the prevalence of clarithromycin resistance by study site, gender, age, or race/ethnicity. In a subset of 67 patients that had clinical follow-up data, the overall prevalence of clarithromycin resistance was 31.3 %. There was a 2.9-fold increase (p = 0.002) in treatment failure for cases with clarithromycin resistance (57.1 %) compared to wildtype H. pylori (19.6 %).

Conclusions

H. pylori clarithromycin resistance in the USA exceeds the estimated 20 % prevalence compatible with successful empiric antibiotic therapy. This resistance resulted in a significant rate of treatment failure in all sites surveyed. Empiric therapy in the USA should be used with caution until there is better regional or local determination of H. pylori antibiotic resistance.

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References

  1. Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345:784–789.

    Article  CAS  PubMed  Google Scholar 

  2. Fukase K, Kato M, Kikuchi S, et al. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet. 2008;372:392–397.

    Article  PubMed  Google Scholar 

  3. Marshall BJ, Goodwin CS, Warren JR, et al. Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter pylori. Lancet. 1988;2:1437–1442.

    Article  CAS  PubMed  Google Scholar 

  4. Gerrits MM, van Vliet AH, Kuipers EJ, Kusters JG. Helicobacter pylori and antimicrobial resistance: molecular mechanisms and clinical implications. Lancet Infect Dis. 2006;6:699–709.

    Article  CAS  PubMed  Google Scholar 

  5. Koletzko S, Jones NL, Goodman KJ, et al. Evidence-based guidelines from ESPGHAN and NASPGHAN for Helicobacter pylori infection in children. J Pediatr Gastroenterol Nutr. 2011;53:230–243.

    PubMed  Google Scholar 

  6. Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pylori infection—the Maastricht IV/Florence consensus report. Gut. 2012;61:646–664.

    Article  CAS  PubMed  Google Scholar 

  7. Mitui M, Patel A, Leos NK, Doern CD, Park JY. Novel Helicobacter pylori sequencing test identifies high rate of clarithromycin resistance. J Pediatr Gastroenterol Nutr. 2014;59:6–9.

    Article  CAS  PubMed  Google Scholar 

  8. Wang G, Taylor DE. Site-specific mutations in the 23S rRNA gene of Helicobacter pylori confer two types of resistance to macrolide-lincosamide-streptogramin B antibiotics. Antimicrob Agents Chemother. 1998;42:1952–1958.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Chey WD, Wong BC. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102:1808–1825.

    Article  CAS  PubMed  Google Scholar 

  10. Schmitt BH, Regner M, Mangold KA, Thomson RB Jr, Kaul KL. PCR detection of clarithromycin-susceptible and -resistant Helicobacter pylori from formalin-fixed, paraffin-embedded gastric biopsies. Mod Pathol. 2013;26:1222–1227.

    Article  CAS  PubMed  Google Scholar 

  11. Shiota S, Reddy R, Alsarraj A, El-Serag HB, Graham DY. Antibiotic Resistance of Helicobacter pylori Among Male United States Veterans. Clin Gastroenterol Hepatol. 2015;13:1616–1624.

    Article  CAS  PubMed  Google Scholar 

  12. Bruce MG, Bruden DL, McMahon BJ, et al. Alaska sentinel surveillance for antimicrobial resistance in Helicobacter pylori isolates from Alaska native persons, 1999–2003. Helicobacter. 2006;11:581–588.

    Article  CAS  PubMed  Google Scholar 

  13. Tveit AH, Bruce MG, Bruden DL, et al. Alaska sentinel surveillance study of Helicobacter pylori isolates from Alaska Native persons from 2000 to 2008. J Clin Microbiol. 2011;49:3638–3643.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Graham DY, Shiotani A. Which therapy for Helicobacter pylori infection? Gastroenterology. 2012;143:10–12.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Meyer JM, Silliman NP, Wang W, et al. Risk factors for Helicobacter pylori resistance in the United States: the surveillance of H. pylori antimicrobial resistance partnership (SHARP) study, 1993–1999. Ann Intern Med. 2002;136:13–24.

    Article  PubMed  Google Scholar 

  16. Osato MS, Reddy R, Reddy SG, Penland RL, Malaty HM, Graham DY. Pattern of primary resistance of Helicobacter pylori to metronidazole or clarithromycin in the United States. Arch Intern Med. 2001;161:1217–1220.

    Article  CAS  PubMed  Google Scholar 

  17. Duck WM, Sobel J, Pruckler JM, et al. Antimicrobial resistance incidence and risk factors among Helicobacter pylori-infected persons, United States. Emerg Infect Dis. 2004;10:1088–1094.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 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.

    Article  CAS  PubMed  Google Scholar 

  19. 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 

  20. Cambau E, Allerheiligen V, Coulon C, et al. Evaluation of a new test, genotype HelicoDR, for molecular detection of antibiotic resistance in Helicobacter pylori. J Clin Microbiol. 2009;47:3600–3607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Juttner S, Vieth M, Miehlke S, et al. Reliable detection of macrolide-resistant Helicobacter pylori via fluorescence in situ hybridization in formalin-fixed tissue. Mod Pathol. 2004;17:684–689.

    Article  PubMed  Google Scholar 

  22. Lottspeich C, Schwarzer A, Panthel K, Koletzko S, Russmann H. Evaluation of the novel Helicobacter pylori ClariRes real-time PCR assay for detection and clarithromycin susceptibility testing of H. pylori in stool specimens from symptomatic children. J Clin Microbiol. 2007;45:1718–1722.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Cosme A, Montes M, Martos M, et al. Usefulness of antimicrobial susceptibility in the eradication of Helicobacter pylori. Clin Microbiol Infect. 2013;19:379–383.

    Article  CAS  PubMed  Google Scholar 

  24. Graham DY, Shiotani A. New concepts of resistance in the treatment of Helicobacter pylori infections. Nat Clin Pract Gastroenterol Hepatol. 2008;5:321–331.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. http://seer.cancer.gov/statfacts/html/stomach.html. Last Accessed January 19, 2016.

  26. Ford AC, Forman D, Hunt R, Yuan Y, Moayyedi P. Helicobacter pylori eradication for the prevention of gastric neoplasia. Cochrane Database Syst Rev. 2015;7:CD005583.

    PubMed  Google Scholar 

  27. Shiotani A, Cen P, Graham DY. Eradication of gastric cancer is now both possible and practical. Semin Cancer Biol. 2013;23:492–501.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank David Y. Graham, MD, Baylor College of Medicine, for assistance in the development of the clarithromycin resistance test (23S rRNA).

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Correspondence to Jason Y. Park.

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The authors declare no personal or funding interests.

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Park, J.Y., Dunbar, K.B., Mitui, M. et al. Helicobacter pylori Clarithromycin Resistance and Treatment Failure Are Common in the USA. Dig Dis Sci 61, 2373–2380 (2016). https://doi.org/10.1007/s10620-016-4091-8

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  • DOI: https://doi.org/10.1007/s10620-016-4091-8

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