Tailored triple plus bismuth therapy based on previous antibiotic medication history for first-line Helicobacter pylori eradication: A randomized trial

Published:January 14, 2023DOI:



      There are no randomized controlled trials that demonstrate the role of tailored therapy based on past medication history in improving efficacy of H. pylori eradication compared to empiric therapies. The objective of this study was to determine whether tailored triple plus bismuth therapy (TBT) can achieve higher eradication rates based on previous antibiotic history than empiric TBTs.


      800 treatment-naïve patients were randomly assigned to four groups receiving clarithromycin-, levofloxacin- or metronidazole-containing empiric TBT and tailored TBT (clarithromycin and levofloxacin chosen based on previous macrolides and quinolones medication history). Correlation analyses were performed between past medication history and resistance or eradication rate.


      The eradication rates of tailored TBT were significantly higher than clarithromycin-, levofloxacin- and metronidazole-containing empiric TBT in both intention-to-treat (89.5%, 80.8%, 81.5% and 81.5%) and per-protocol (95.1%, 86.7%, 86.5% and 87.8%) analyses (P<0.05). In patients with previous macrolides, quinolones or nitroimidazoles medication history, the resistance rates of corresponding clarithromycin, levofloxacin or metronidazole were significantly higher than patients without past medication history, and the eradication rates of corresponding clarithromycin- or levofloxacin-containing empiric TBT were significantly lower.


      Tailored TBT based on previous antibiotic history can achieve higher eradication rates than empiric TBT for first-line H. pylori eradication.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Digestive and Liver Disease
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Savoldi A.
        • Carrara E.
        • Graham D.Y.
        • et al.
        Prevalence of antibiotic resistance in helicobacter pylori: a systematic review and meta-analysis in world health organization regions.
        Gastroenterology. 2018; 155 (e17): 1372-1382
        • Sugano K.
        • Tack J.
        • Kuipers E.J.
        • et al.
        Kyoto global consensus report on Helicobacter pylori gastritis.
        Gut. 2015; 64: 1353-1367
        • Malfertheiner P.
        • Megraud F.
        • Rokkas T.
        • et al.
        Management of helicobacter pylori infection: the Maastricht VI/Florence consensus report.
        Gut. 2022; 71: 1724-1762
        • Song Z.Q.
        • Zhou L.Y
        Helicobacter pylori and gastric cancer: clinical aspects.
        Chin Med J (Engl). 2015; 128: 3101-3105
        • Liu W.Z.
        • Xie Y.
        • Lu H.
        • et al.
        Fifth Chinese national consensus report on the management of helicobacter pylori infection.
        Helicobacter. 2018; 23: e12475
        • Malfertheiner P.
        • Megraud F.
        • O'Morain C.A.
        • et al.
        Management of helicobacter pylori infection-the Maastricht V/Florence consensus report.
        Gut. 2017; 66: 6-30
        • Zhou L.
        • Zhang J.
        • Song Z.
        • et al.
        Tailored versus triple plus bismuth or concomitant therapy as initial helicobacter pylori treatment: a randomized trial.
        Helicobacter. 2016; 21: 91-99
        • Song Z.Q.
        • Zhou L.Y
        Hybrid, sequential and concomitant therapies for Helicobacter pylori eradication: a systematic review and meta-analysis.
        World J Gastroenterol. 2016; 22: 4766-4775
        • Zhang W.
        • Chen Q.
        • Liang X.
        • et al.
        Bismuth, lansoprazole, amoxicillin and metronidazole or clarithromycin as first-line Helicobacter pylori therapy.
        Gut. 2015; 64: 1715-1720
        • Liao J.
        • Zheng Q.
        • Liang X.
        • et al.
        Effect of fluoroquinolone resistance on 14-day levofloxacin triple and triple plus bismuth quadruple therapy.
        Helicobacter. 2013; 18: 373-377
        • Ke H.
        • Li J.
        • Lu B.
        • et al.
        The appropriate cutoff gastric pH value for Helicobacter pylori eradication with bismuth-based quadruple therapy.
        Helicobacter. 2021; 26: e12768
        • McNicholl A.G.
        • Bordin D.S.
        • Lucendo A.
        • et al.
        Combination of Bismuth and standard triple therapy eradicates helicobacter pylori infection in more than 90% of patients.
        Clin Gastroenterol Hepatol. 2020; 18: 89-98
        • Goossens H
        Antibiotic consumption and link to resistance.
        Clin Microbiol Infect. 2009; 15 Suppl 3: 12-15
        • Graham D.Y.
        • Moss S.F
        Antimicrobial susceptibility testing for helicobacter pylori is now widely available: when, how, why.
        Am J Gastroenterol. 2022; 117: 524-528
        • Fallone C.A.
        • Moss S.F.
        • Malfertheiner P
        Reconciliation of recent helicobacter pylori treatment guidelines in a time of increasing resistance to antibiotics.
        Gastroenterology. 2019; 157: 44-53
        • Graham D.Y.
        • Lee Y.C.
        • Wu M.S
        Rational Helicobacter pylori therapy: evidence-based medicine rather than medicine-based evidence.
        Clin Gastroenterol Hepatol. 2014; 12 (e3; Discussion e12-3): 177-186
        • Chey W.D.
        • Leontiadis G.I.
        • Howden C.W.
        • et al.
        ACG clinical guideline: treatment of helicobacter pylori infection.
        Am J Gastroenterol. 2017; 112: 212-239
        • 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
        • Furuta T.
        • Graham D.Y
        Pharmacologic aspects of eradication therapy for helicobacter pylori infection.
        Gastroenterol Clin North Am. 2010; 39: 465-480
        • Boltin D.
        • Levi Z.
        • Gingold-Belfer R.
        • et al.
        Impact of previous exposure to macrolide antibiotics on helicobacter pylori infection treatment outcomes.
        Am J Gastroenterol. 2019; 114: 900-906
        • Boltin D.
        • Levi Z.
        • Gingold-Belfer R.
        • et al.
        Effect of previous nitroimidazole treatment on helicobacter pylori eradication success.
        J Clin Gastroenterol. 2020; 54: 333-337
        • Munoz-Gomez P.
        • Jordan-Castro J.A.
        • Abanades-Tercero M.
        • et al.
        Macrolide use in the previous years is associated with failure to eradicate Helicobacter pylori with clarithromycin-containing regimens.
        Helicobacter. 2018; : 23
        • Lim S.G.
        • Park R.W.
        • Shin S.J.
        • et al.
        The relationship between the failure to eradicate Helicobacter pylori and previous antibiotics use.
        Dig Liver Dis. 2016; 48: 385-390
        • McMahon B.J.
        • Hennessy T.W.
        • Bensler J.M.
        • et al.
        The relationship among previous antimicrobial use, antimicrobial resistance, and treatment outcomes for Helicobacter pylori infections.
        Ann Intern Med. 2003; 139: 463-469
        • Kocsmar E.
        • Buzas G.M.
        • Szirtes I.
        • et al.
        Primary and secondary clarithromycin resistance in Helicobacter pylori and mathematical modeling of the role of macrolides.
        Nat Commun. 2021; 12: 2255
        • Perez Aldana L.
        • Kato M.
        • Nakagawa S.
        • et al.
        The relationship between consumption of antimicrobial agents and the prevalence of primary Helicobacter pylori resistance.
        Helicobacter. 2002; 7: 306-309
        • Banatvala N.
        • Davies G.R.
        • Abdi Y.
        • et al.
        High prevalence of Helicobacter pylori metronidazole resistance in migrants to east London: relation with previous nitroimidazole exposure and gastroduodenal disease.
        Gut. 1994; 35: 1562-1566
        • Graham D.Y.
        • Megraud F
        Classification system for Helicobacter pylori therapies: compared and contrasted to traditional infectious disease therapy.
        Helicobacter. 2021; 26: e12773
        • Graham D.Y.
        • Dore M.P.
        • Lu H
        Understanding treatment guidelines with bismuth and non-bismuth quadruple Helicobacter pylori eradication therapies.
        Expert Rev Anti Infect Ther. 2018; 16: 679-687
        • Graham D.Y.
        • Lee S.Y
        How to effectively use bismuth quadruple therapy: the good, the bad, and the ugly.
        Gastroenterol Clin North Am. 2015; 44: 537-563
        • Graham D.Y.
        • Liou J.M
        Primer for development of guidelines for helicobacter pylori therapy using antimicrobial stewardship.
        Clin Gastroenterol Hepatol. 2022; 20 (e1): 973-983
        • Dixon M.F.
        • Genta R.M.
        • Yardley J.H.
        • et al.
        Classification and grading of gastritis. The updated Sydney system. International workshop on the histopathology of gastritis, Houston 1994.
        Am J Surg Pathol. 1996; 20: 1161-1181
        • Sahu C.
        • Jain V.
        • Mishra P.
        • et al.
        Clinical and laboratory standards institute versus European committee for antimicrobial susceptibility testing guidelines for interpretation of carbapenem antimicrobial susceptibility results for Escherichia coli in urinary tract infection (UTI).
        J Lab Physicians. 2018; 10: 289-293
        • Song Z.
        • Zhou L.
        • Xue Y.
        • et al.
        A comparative study of 14-day dual therapy (esomeprazole and amoxicillin four times daily) and triple plus bismuth therapy for first-line Helicobacter pylori infection eradication: a randomized trial.
        Helicobacter. 2020; 25: e12762
        • McNulty C.A.
        • Lasseter G.
        • Shaw I.
        • et al.
        Is Helicobacter pylori antibiotic resistance surveillance needed and how can it be delivered?.
        Aliment Pharmacol Ther. 2012; 35: 1221-1230
        • Romano M.
        • Gravina A.G.
        • Nardone G.
        • et al.
        Non-bismuth and bismuth quadruple therapies based on previous clarithromycin exposure are as effective and safe in an area of high clarithromycin resistance: a real-life study.
        Helicobacter. 2020; 25: e12694
        • Liou J.M.
        • Chen P.Y.
        • Kuo Y.T.
        • et al.
        Toward population specific and personalized treatment of Helicobacter pylori infection.
        J Biomed Sci. 2018; 25: 70