Retrospective Analysis Confirms Tetracycline Quadruple as Best Helicobacter pylori Regimen in the USA

  • Mohd Amer Alsamman
  • Eric C. Vecchio
  • Khaled Shawwa
  • Gabriel Acosta-Gonzales
  • Murray B. Resnick
  • Steven F. MossEmail author
Original Article



Declining Helicobacter pylori (H. pylori) eradication rates have prompted a switch in first-line therapy from standard triple (PPI, clarithromycin, and amoxicillin) to bismuth-based quadruple therapy. A caveat of the ACG 2017 H. pylori treatment guidelines was a paucity of recent US eradication data.


To determine Rhode Island H. pylori eradication data, in the largest US study from the last two decades.


Electronic records were queried for patients with H. pylori infection diagnosed by pathology, urea breath test, or stool antigen from 2015 to 2017. Demographics, diagnostic test, treatment regimen, and test of cure were extracted. Eradication rates were calculated, and treatment regimens were compared.


A total of 1710 patients were identified (64% female): 825 (46%) diagnosed by breath test, 755 (42%) by biopsy, and 191 (12%) by stool antigen. Full data were obtained on 1101 patients. Seven regimens were used: quadruple (64%), triple (25%), doxycycline quadruple (5%), and miscellaneous (6%). Quadruple was superior to triple: (85% vs. 75%, P = 0.002), quadruple 14 days versus triple 14 days (87% vs. 79%, P = 0.0052), quadruple 10 days versus triple 10 days (77% vs. 67%, P = 0.33). Increased therapy length improved eradication (quadruple 14 days  vs. 10 days, 87% vs. 77%, P = 0.002; triple 14 days  versus 10 days 79% vs. 67%, P = 0.13). Finally, substituting doxycycline for tetracycline yielded lower eradication (85% vs. 67%, P = 0.006).


Quadruple therapy is superior to triple therapy within the Rhode Island population. Fourteen-day therapy achieves superior eradication compared to 10-day therapy, and doxycycline is inferior to tetracycline for quadruple therapy. Our findings support adherence to ACG and international guidelines advising 14-day quadruple therapy.


Helicobacter pylori Stomach USA Gastrointestinal infections Eradication therapy 



American College of Gastroenterology


Proton pump inhibitor


Test of cure


Urea breath test


Author’s contribution

All authors contributed substantially to the manuscript. Dr. SFM conceived and supervised the study and Drs. MAA and SFM wrote the IRB proposal. Dr. MAA, Dr. ECV and Dr. GA-G performed chart review and data collection. Dr. KS and Dr. MAA performed all statistical analysis with input from Dr. SFM., Dr. MAA, and Dr. ECV wrote the initial draft of the manuscript with critical input from Dr. SFM and all other listed authors. Each author read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of interest

Dr Moss receives grant support from American Molecular Laboratories for an unrelated clinical study. There were no other financial, professional, or personal conflicts of interests to declare on behalf of all authors.


  1. 1.
    NIH Consensus Conference. Helicobacter pylori in peptic ulcer disease. NIH consensus development panel on Helicobacter pylori in Peptic ulcer disease. JAMA. 1994;272:65–69.CrossRefGoogle Scholar
  2. 2.
    McColl KEL. Clinical practice. Helicobacter pylori infection. N Engl J Med. 2010;362:1597–1604.CrossRefGoogle Scholar
  3. 3.
    Graham DY, Fischbach L. Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut. 2010;59:1143–1153.CrossRefGoogle Scholar
  4. 4.
    Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017;112:212–239.CrossRefGoogle Scholar
  5. 5.
    Malfertheiner P, Megraud F, O'Morain CA, et al. Management of Helicobacter pylori infection-the Maastricht V/Florence consensus report. Gut. 2017;66:6–30.CrossRefGoogle Scholar
  6. 6.
    Fallone CA, Chiba N, van Zanten SV, et al. The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology. 2016;151:51.e14–69.e14.CrossRefGoogle Scholar
  7. 7.
    Laine L, Fennerty MB, 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;95:3393–3398.CrossRefGoogle Scholar
  8. 8.
    Vakil N, Lanza F, Schwartz H, Barth J. Seven-day therapy for Helicobacter pylori in the United States. Aliment Pharmacol Ther. 2004;20:99–107.CrossRefGoogle Scholar
  9. 9.
    Liou J-M, Fang YJ, Chen CC, et al. Concomitant, bismuth quadruple, and 14-day triple therapy in the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet. 2016;388:2355–2365.CrossRefGoogle Scholar
  10. 10.
    Liu RP, Romero R, Sarosiek J, Dodoo C, Dwivedi AK, Zuckerman MJ. Eradication rate of Helicobacter pylori on the US-Mexico border using the urea breath test. South Med J. 2018;111:51–55.CrossRefGoogle Scholar
  11. 11.
    Rubin J, Lai A, Dulai P, Gupta S, Crowe SE. Low rates of H. pylori eradication testing and cure rates in usual care (abstract). Gastroenterology. 2018;154:S-503–S-504.CrossRefGoogle Scholar
  12. 12.
    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.CrossRefGoogle Scholar
  13. 13.
    Nayar DS. Current eradication rate of Helicobacter pylori with clarithromycin-based triple therapy in a gastroenterology practice in the New York metropolitan area. Infect Drug Resist. 2018;11:205–211.CrossRefGoogle Scholar
  14. 14.
    Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in World Health Organization regions. Gastroenterology. 2018;155:1372.e17–1382.e17.CrossRefGoogle Scholar
  15. 15.
    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.CrossRefGoogle Scholar
  16. 16.
    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.CrossRefGoogle Scholar
  17. 17.
    Park JY, Dunbar KB, Mitui M, et al. Helicobacter pylori Clarithromycin resistance and treatment failure are common in the USA. Dig Dis Sci. 2016;61:2373–2380.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Hospital Medicine, The Miriam HospitalThe Warren Alpert Medical School of Brown UniversityProvidenceUSA
  2. 2.Internal Medicine, Rhode Island HospitalThe Warren Alpert Medical School of Brown UniversityProvidenceUSA
  3. 3.Division of Nephrology and HypertensionMayo ClinicRochesterUSA
  4. 4.Department of Pathology, Rhode Island HospitalThe Warren Alpert Medical School of Brown UniversityProvidenceUSA
  5. 5.Division of Gastroenterology, Rhode Island HospitalThe Warren Alpert Medical School of Brown UniversityProvidenceUSA

Personalised recommendations