{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T10:45:38Z","timestamp":1782297938692,"version":"3.54.5"},"reference-count":39,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T00:00:00Z","timestamp":1623196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>As high clarithromycin resistance (&gt;20%) in the Split-Dalmatia region of Croatia hinders the treatment of H. pylori infection, the primary objective of this study was to compare concomitant quadruple with the tailored, personalized therapy as first-line eradication treatment of H. pylori. In an open-label, randomized clinical trial, 80 patients with H. pylori infection were randomly assigned to either concomitant (esomeprazole 40 mg, amoxicillin 1 gr, metronidazole 500 mg, clarithromycin 500 mg, twice daily for 14 days) or tailored therapy in accordance with the results of the antimicrobial susceptibility testing. Eradication status was assessed 4 weeks after treatment. Eradication rates were significantly higher in tailored group than in concomitant group both in intention-to-treat (70 vs. 92.5%, p = 0.010) and per-protocol (87.5 vs. 100%, p = 0.030) analysis in the setting of increasing antibiotic resistance (clarithromycin 37.5%, metronidazole 17.5%, dual resistance 10%). Adverse effects were more frequent in the concomitant group (32.5 vs. 7.5%, p = 0.006). Tailored therapy achieves higher eradication with a lower adverse events rate. With the increasing resistance of H. pylori strains to antibiotic treatment, eradication regimes with such characteristics should be strongly considered as a reasonable choice for first-line treatment.<\/jats:p>","DOI":"10.3390\/jpm11060534","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T14:16:04Z","timestamp":1623248164000},"page":"534","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Randomized Clinical Trial Comparing Concomitant and Tailored Therapy for Eradication of Helicobacter pylori Infection"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3427-2920","authenticated-orcid":false,"given":"Nikola","family":"Perkovic","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, University Hospital of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Mestrovic","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Hospital of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1634-0635","authenticated-orcid":false,"given":"Josko","family":"Bozic","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8878-7164","authenticated-orcid":false,"given":"Mirela Pavicic","family":"Ivelja","sequence":"additional","affiliation":[{"name":"Department for Infectious Diseases, University Hospital of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonatan","family":"Vukovic","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Hospital of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goran","family":"Kardum","sequence":"additional","affiliation":[{"name":"Department of Psychology, Faculty of Humanities and Social Sciences, University of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeljko","family":"Sundov","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Hospital of Split, 21000 Split, Croatia"},{"name":"Department of Internal Medicine, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Tonkic","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, University Hospital of Split, 21000 Split, Croatia"},{"name":"Department of Medical Microbiology and Parasitology, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeljko","family":"Puljiz","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Hospital of Split, 21000 Split, Croatia"},{"name":"Department of Internal Medicine, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2182-2890","authenticated-orcid":false,"given":"Katarina","family":"Vukojevic","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ante","family":"Tonkic","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Hospital of Split, 21000 Split, Croatia"},{"name":"Department of Internal Medicine, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nrgastro.2013.96","article-title":"Helicobacter pylori research: Historical insights and future directions","volume":"10","author":"Fock","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1136\/gut.2009.192757","article-title":"Helicobacter pylori treatment in the era of increasing of antibiotic resistance","volume":"59","author":"Graham","year":"2010","journal-title":"Gut"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3322\/caac.21262","article-title":"Global Cancer Statistics, 2012","volume":"65","author":"Torre","year":"2015","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/ijc.28999","article-title":"Global burden of gastric cancer attributable to Helicobacter pylori","volume":"136","author":"Plummer","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1007\/s10620-006-9566-6","article-title":"Alcohol dehydrogenase (ADH) isoenzymes activity in the sera of patients with Helicobacter pylori infection","volume":"52","author":"Wojciech","year":"2007","journal-title":"Dig. Dis. Sci."},{"key":"ref_6","first-page":"951","article-title":"The alcohol dehydrogenase isoenzyme alcohol dehydrogenase IV as a candidate marker of Helicobacter pylori infection","volume":"10","author":"Wojciech","year":"2014","journal-title":"Arch. Med. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1136\/gutjnl-2015-309252","article-title":"Kyoto global consensus report on Helicobacter pylori gastritis","volume":"64","author":"Sugano","year":"2015","journal-title":"Gut"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Graham, D.Y. (2020). Transitioning of Helicobacter pylori Therapy from Trial and Error to Antimicrobial Stewardship. Antibiotics, 9.","DOI":"10.3390\/antibiotics9100671"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1093\/jac\/dku243","article-title":"Prospective multicentre study on antimicrobial resistance of Helicobacter pylori in Germany","volume":"69","author":"Draeger","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1179\/1973947812Y.0000000001","article-title":"Time trends of primary antibiotic resistance of Helicobacter pylori isolates in Southern Croatia","volume":"24","author":"Tonkic","year":"2012","journal-title":"J. Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1093\/infdis\/jit287","article-title":"Eradication of Helicobacter pylori according to 23S ribosomal RNA point mutations associated with clarithromycin resistance","volume":"208","author":"Lee","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/hel.12242","article-title":"Tailored versus triple plus bismuth or concomitant therapy as initial Helicobacter pylori treatment: A randomized trial","volume":"21","author":"Zhou","year":"2015","journal-title":"Helicobacter"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"270","DOI":"10.3109\/00365521.2015.1095352","article-title":"Comparison of the efficacy of culture-based tailored therapy for Helicobacter pylori eradication with that of the traditional second-line rescue therapy in Korean patients: A prospective single tertiary center study","volume":"51","author":"Lee","year":"2016","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1136\/gutjnl-2012-302254","article-title":"Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption","volume":"62","author":"Megraud","year":"2012","journal-title":"Gut"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/j.1365-2036.2011.04770.x","article-title":"Review article: Non-bismuth quadruple (concomitant) therapy for Helicobacter pylori eradication","volume":"34","author":"Gisbert","year":"2011","journal-title":"Aliment Pharmacol. There"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mestrovic, A., Perkovic, N., Bozic, J., Ivelja, M.P., Vukovic, J., Kardum, G., Puljiz, Z., and Tonkic, A. (2020). Randomised clinical trial comparing concomitant and hybrid therapy for eradication of Helicobacter pylori infection. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0244500"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"351","DOI":"10.3748\/wjg.v21.i1.351","article-title":"Concomitant therapy achieved the best eradication rate for Helicobacter pylori among various treatment strategies","volume":"21","author":"Lee","year":"2015","journal-title":"World J. Gastroen."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"23","DOI":"10.2147\/CEG.S25419","article-title":"Update on non-bismuth quadruple (concomitant) therapy for eradication of Helicobacter pylori","volume":"5","author":"Gisbert","year":"2012","journal-title":"Clin. Exp. Gastroenterol."},{"key":"ref_19","unstructured":"Dolinar, U., Plut, S., \u0160tabuc, B., Homan, M., Tepe\u0161, B., and Jeverica, S. (2015, January 25\u201328). Primary and secondary resistance of Helicobacter pylori in Slovenia, 2011\u20132014. Proceedings of the 25th European Congress of Clinical Microbiology and Infectious Diseases, Copenhagen, Denmark. Available online: https:\/\/www.escmid.org\/escmid_publications\/escmid_elibrary\/."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1128\/CMR.00033-06","article-title":"Helicobacter pylori detection and antimicrobial susceptibility testing","volume":"20","author":"Megraud","year":"2007","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.1111\/j.1572-0241.2000.03317.x","article-title":"Pretreatment antimicrobial-susceptibility testing in the eradication of H. pylori infection","volume":"95","author":"Romano","year":"2000","journal-title":"Am. J. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1179\/joc.2006.18.4.437","article-title":"Primary resistance and antibiotic minimum inhibitory concentrations for Helicobacter pylori strains, in Split, Croatia","volume":"18","year":"2006","journal-title":"J. Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1136\/gutjnl-2016-312288","article-title":"Management ofHelicobacter pyloriinfection\u2014the Maastricht V\/Florence Consensus Report","volume":"66","author":"Malfertheiner","year":"2016","journal-title":"Gut"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1136\/gutjnl-2012-302084","article-title":"Management of Helicobacter pylori infection--the Maastricht IV\/ Florence Consensus Report","volume":"61","author":"Malfertheiner","year":"2012","journal-title":"Gut"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/j.1523-5378.2009.00671.x","article-title":"Meta-analysis: Four-drug, three-antibiotic, non-bismuth-containing \u201cconcomitant therapy\u201d versus triple therapy for Helicobacter pylori eradication","volume":"14","author":"Essa","year":"2009","journal-title":"Helicobacter"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fallone, C.A., Chiba, N., van Zanten, S.V., Fischbach, L., Gisbert, J.P., Hunt, R.H., Jones, N.L., and Marshall, J.K. (2016). The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults. Gastroenterology, 151.","DOI":"10.1053\/j.gastro.2016.04.006"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.cgh.2009.09.030","article-title":"Sequential and concomitant therapy with 4 drugs are equally effective for H","volume":"8","author":"Wu","year":"2010","journal-title":"pylori infection. Clin. Gastroenterol. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1136\/gutjnl-2015-310142","article-title":"Sequential therapy for 10 days versus triple therapy for 14 days in the eradication of Helicobacter pylori in the community and hospital populations: A randomised trial","volume":"65","author":"Liou","year":"2016","journal-title":"Gut"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.gtc.2010.08.007","article-title":"Pharmacologic aspects of eradication therapy for Helicobacter pylori infection","volume":"39","author":"Furuta","year":"2010","journal-title":"Gastroenterol. Clin. N. Am."},{"key":"ref_30","first-page":"647","article-title":"Slovenian society for gastroenterology and hepatology guidelines on the management of Helicobacter pylori infection","volume":"80","year":"2011","journal-title":"Zdrav. Vestn."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ebiom.2018.08.028","article-title":"The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: An open-label, randomized clinical trial","volume":"35","author":"Chen","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.2169\/internalmedicine.49.3031","article-title":"Is Antimicrobial Susceptibility Testing Necessary Before First-line Treatment for Helicobacter pylori Infection? Meta-analysis of Randomized Controlled Trials-","volume":"49","author":"Wenzhen","year":"2010","journal-title":"Intern. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/sj.clpt.6100043","article-title":"Pharmacogenomics-based Tailored Versus Standard Therapeutic Regimen for Eradication of H. pylori","volume":"81","author":"Furuta","year":"2007","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1469-0691.2012.03844.x","article-title":"Usefulness of antimicrobial susceptibility in the eradication of Helicobacter pylori","volume":"19","author":"Cosme","year":"2013","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1038\/ajg.2014.222","article-title":"Pretreatment antimicrobial susceptibility-guided vs. clarithromycin-based triple therapy for Helicobacter pylori eradication in a region with high rates of multiple drug resistance","volume":"109","author":"Park","year":"2014","journal-title":"Am. J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1093\/jac\/dkv155","article-title":"Systematic review and meta-analysis: Susceptibility-guided versus empirical antibiotic treatment for Helicobacter pylori infection","volume":"70","author":"Puig","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1111\/j.1572-0241.1999.00943.x","article-title":"Costs of diagnosis and treatment of Helicobacter pylori infection: When does choosing the treatment regimen based on susceptibility testing become cost effective?","volume":"94","author":"Breuer","year":"1999","journal-title":"Am. J. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S1542-3565(03)00131-9","article-title":"Pretreatment antimicrobial susceptibility testing is cost saving in the eradication of Helicobacter pylori","volume":"1","author":"Romano","year":"2003","journal-title":"Clin. Gastroen. Hepat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/hel.12244","article-title":"Avoiding unethical Helicobacter pylori clinical trials: Susceptibility-based studies and probiotics as adjuvants","volume":"20","author":"Graham","year":"2015","journal-title":"Helicobacter"}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/11\/6\/534\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:12:39Z","timestamp":1760163159000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/11\/6\/534"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,9]]},"references-count":39,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["jpm11060534"],"URL":"https:\/\/doi.org\/10.3390\/jpm11060534","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,9]]}}}