Empiric Versus Clarithromycin Resistance-Guided Therapy for Helicobacter pylori Based on Polymerase Chain Reaction Results in Patients With Gastric Neoplasms or Gastric Mucosa-Associated Lymphoid Tissue Lymphoma: A Randomized Controlled Trial

Jue Lie Kim, Soo-Jeong Cho, Su Jin Chung, Ayoung Lee, Jinju Choi, Hyunsoo Chung, Sang Gyun Kim, Jue Lie Kim, Soo-Jeong Cho, Su Jin Chung, Ayoung Lee, Jinju Choi, Hyunsoo Chung, Sang Gyun Kim

Abstract

Introduction: We investigated to compare the effect of empirical therapy vs clarithromycin resistance-guided tailored therapy (tailored therapy) for eradication of Helicobacter pylori.

Methods: In this prospective, single center, open-label randomized controlled trial, we enrolled 72 patients with H. pylori infection from January 2019 through June 2019 in Korea. The patients were randomly assigned to both groups received empirical (n = 36) or tailored therapy (n = 36). Empirical therapy was defined as triple therapy with esomeprazole, amoxicillin, and clarithromycin for 10 days irrespective of clarithromycin resistance. Tailored therapy was triple or quadruple therapy with esomeprazole, metronidazole, tetracycline, and bismuth for 10 days based on genotype markers of resistance determined by gastric biopsy. Resistance-associated mutations in 23S rRNA were confirmed by multiplex polymerase chain reaction. Eradication status was assessed by C-urea breath test, and the primary outcome was eradication rates.

Results: H. pylori was eradicated in 27 patients (75.0%), given empirical therapy and 32 patients (88.9%) treated with tailored therapy (P = 0.136) in intention-to-treat analysis. In per protocol analysis, the eradication rate was 97.0% and 81.8% in tailoredvs empirical groups (P = 0.046). Although clarithromycin-resistant H. pylori was eradicated in 3/9 (33.3%) with empirical therapy, it was treated in 11/12 (91.7%) with tailored therapy (P = 0.009). There was no difference in compliance between 2 groups. The rate of adverse events of the tailored group was higher than that of the empirical group (P = 0.036) because quadruple therapy had more side effects than those of triple therapy (P = 0.001).

Discussion: Tailored therapy based on polymerase chain reaction is a good alternative to increase eradication rates in a region of high prevalence of clarithromycin resistance (see Visual Abstract, Supplementary Digital Content 1, http://links.lww.com/CTG/A342).

Trial registration: ClinicalTrials.gov NCT04006340.

Conflict of interest statement

Guarantor of the article: Soo-Jeong Cho, MD, PhD.

Specific author contributions: J.L.K., S.-J.C.: planning and/or conducting the study. J.L.K., S.-J.C., S.J.C., A.L., J.C., H.C.: collecting and/or interpreting data. J.L.K., S.-J.C., S.G.K.: drafting/revision of the manuscript. J.L.K., S.-J.C., S.J.C., A.L., J.C., H.C., S.G.K.: approval of the final draft of the submitted manuscript.

Financial support: This study was supported by a grant from the National Research Foundation of Korea (#NRF-2019R1A2C1009923) and the Korean Gastroenterology Fund for Future Development (2018). The work was independently conducted of the funding source. The funding source played no role in the report of this trial.

Potential competing interests: None to report.

Clinical trial registration: NCT04006340.

Figures

Figure 1.
Figure 1.
Enrollment, randomization, and follow-up. GS, general surgery; MALT, mucosa-associated lymphoid tissue; PCR, polymerase chain reaction.

References

    1. Choi JM, Kim SG. Diagnosis and treatment of Helicobacter pylori infection: Korean and overseas guidelines. Korean J Med 2015;89:157–68.
    1. Chey WD, Leontiadis GI, Howden CW, et al. ACG clinical guideline: Treatment of Helicobacter pylori infection. Am J Gastroenterol 2017;112:212–39.
    1. Kim SG, Jung HK, Lee HL, et al. Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition. J Gastroenterol Hepatol 2014;29:1371–86.
    1. Sugano K, Tack J, Kuipers EJ, et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut 2015;64:1353–67.
    1. Asaka M. A new approach for elimination of gastric cancer deaths in Japan. Int J Cancer 2013;132:1272–6.
    1. Kim BJ, Lee H, Lee YC, et al. Ten-day concomitant, 10-day sequential, and 7-day triple therapy as first-line treatment for Helicobacter pylori infection: A nationwide randomized trial in Korea. Gut Liver 2019;13:531–40.
    1. Gatta L, Vakil N, Vaira D, et al. Global eradication rates for Helicobacter pylori infection: Systematic review and meta-analysis of sequential therapy. BMJ 2013;347:f4587.
    1. 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.
    1. Lee JH, Ahn JY, Choi KD, et al. Nationwide antibiotic resistance mapping of Helicobacter pylori in Korea: A prospective multicenter study. Helicobacter 2019;24:e12592.
    1. Lehours P, Siffré E, Mégraud F. DPO multiplex PCR as an alternative to culture and susceptibility testing to detect Helicobacter pylori and its resistance to clarithromycin. BMC Gastroenterol 2011;11:112.
    1. Woo HY, Park DI, Park H, et al. Dual-priming oligonucleotide-based multiplex PCR for the detection of Helicobacter pylori and determination of clarithromycin resistance with gastric biopsy specimens. Helicobacter 2009;14:22–8.
    1. Hwang TJ, Kim N, Kim HB, et al. Change in antibiotic resistance of Helicobacter pylori strains and the effect of A2143G point mutation of 23S rRNA on the eradication of H. pylori in a single center of Korea. J Clin Gastroenterol 2010;44:536–43.
    1. Graham DY, Shiotani A. New concepts of resistance in the treatment of Helicobacter pylori infections. Nat Rev Gastroenterol Hepatol 2008;5:321.
    1. 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.
    1. Luther J, Higgins PD, Schoenfeld PS, et al. Empiric quadruple vs. triple therapy for primary treatment of Helicobacter pylori infection: Systematic review and meta-analysis of efficacy and tolerability. Am J Gastroenterol 2010;105:65–73.
    1. Lee JH, Park J, Park MR, et al. A comparative study of Helicobacter pylori growth on different agar-based media. Korean J Helicobacter Upper Gastrointest Res 2017;17:208–12.
    1. Lee JY, Kim N. Future trends of Helicobacter pylori eradication therapy in Korea. Korean J Gastroenterol 2014;63:158.
    1. Liou JM, Chen PY, Luo JC, et al. Efficacies of genotypic resistance-guided vs empirical therapy for refractory Helicobacter pylori infection. Gastroenterology 2018;155:1109–19.
    1. Gweon TG, Kim JS, Kim BW. An economic modeling study of Helicobacter pylori eradication: Comparison of dual priming oligonucleotide-based multiplex polymerase chain reaction and empirical treatment. Gut Liver 2018;12:648–54.
    1. Jung YD, Kim Y-J, Chung WC. A pilot study of Helicobacter pylori eradication using a polymerase chain reaction-based test for clarithromycin resistance. Korean J Helicobacter Upper Gastrointest Res 2017;17:200.
    1. Lee HJ, Kim JI, Cheung DY, et al. Eradication of Helicobacter pylori according to 23S ribosomal RNA point mutations associated with clarithromycin resistance. J Infect Dis 2013;208:1123–30.
    1. Bang H, Zhao H. Median-based incremental cost-effectiveness ratio (ICER). J Stat Theory Pract 2012;6:428–42.
    1. Humans Iwgoteocrt. Schistosomes, Liver Flukes and Helicobacter pylori. International Agency for Research on Cancer: Lyon, 1994.
    1. Correa P. Helicobacter pylori and gastric carcinogenesis. Am J Surg Pathol 1995;19:S37–43.
    1. Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med 2002;347:1175–86.
    1. Choi IJ, Kook MC, Kim YI, et al. Helicobacter pylori therapy for the prevention of metachronous gastric cancer. N Engl J Med 2018;378:1085–95.
    1. Choi JM, Kim SG, Choi J, et al. Effects of Helicobacter pylori eradication for metachronous gastric cancer prevention: A randomized controlled trial. Gastrointest Endosc 2018;88:475–85.
    1. Cho SJ, Choi IJ, Kook MC, et al. Randomised clinical trial: The effects of Helicobacter pylori eradication on glandular atrophy and intestinal metaplasia after subtotal gastrectomy for gastric cancer. Aliment Pharmacol Ther 2013;38:477–89.
    1. Venerito M, Krieger T, Ecker T, et al. Meta-analysis of bismuth quadruple therapy versus clarithromycin triple therapy for empiric primary treatment of Helicobacter pylori infection. Digestion 2013;88:33–45.
    1. Rimbara E, Fischbach LA, Graham DY. Optimal therapy for Helicobacter pylori infections. Nat Rev Gastroenterol Hepatol 2011;8:79.
    1. Kim N, Kim JM, Kim CH, et al. Institutional difference of antibiotic resistance of Helicobacter pylori strains in Korea. J Clin Gastroenterol 2006;40:683–7.
    1. Chen H, Dang Y, Zhou X, et al. Tailored therapy versus empiric chosen treatment for Helicobacter pylori eradication: A meta-analysis. Medicine (Baltimore) 2016;95:e2750.
    1. Puig I, Baylina M, Sanchez-Delgado J, et al. Systematic review and meta-analysis: Triple therapy combining a proton-pump inhibitor, amoxicillin and metronidazole for Helicobacter pylori first-line treatment. J Antimicrob Chemother 2016;71(10):2740–53.
    1. Nishizawa T, Maekawa T, Watanabe N, et al. Clarithromycin versus metronidazole as first-line Helicobacter pylori eradication: A multicenter, prospective, randomized controlled study in Japan. J Clin Gastroenterol 2015;49:468–71.
    1. Chung JW, Lee GH, Jeong JY, et al. Resistance of Helicobacter pylori strains to antibiotics in Korea with a focus on fluoroquinolone resistance. J Gastroenterol Hepatol 2012;27(3):493–7.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する