Pediatr Gastroenterol Hepatol Nutr.  2019 Sep;22(5):417-430. 10.5223/pghn.2019.22.5.417.

Changes in the Treatment Strategies for Helicobacter pylori Infection in Children and Adolescents in Korea

• Jun JS
• Seo JH
• Park JS
• Rhee KH
• Youn HS

• KMID: 2457743
• DOI: http://doi.org/10.5223/pghn.2019.22.5.417

Abstract

The policies developed for the treatment of Helicobacter pylori infection in adults may not be the most suitable ones to treat children and adolescents. Methods used to treat children and adolescents in Europe and North America may not be appropriate for treating children and adolescents in Korea due to differences in epidemiological characteristics of H. pylori between regions. Moreover, the agreed standard guidelines for the treatment of H. pylori infection in children and adolescents in Korea have not been established yet. In this study, the optimal treatment strategy for H. pylori infection control in children and adolescents in Korea is discussed based on these guidelines, and recent progress on the use and misuse of antimicrobial agents is elaborated. Non-invasive as well as invasive diagnostic test and treatment strategy for H. pylori infection are not recommendable in children aged less than ten years or children with body weight under 35 kg, except in cases of clinically suspected or endoscopically identified peptic ulcers. The uncertainty, whether enough antimicrobial concentrations to eradicate H. pylori can be maintained when administered according to body weight-based dosing, and the costs and adverse effects outweighing the anticipated benefits of treatment make it difficult to decide to eradicate H. pylori in a positive non-invasive diagnostic test in this age group. However, adolescents over ten years of age or with a bodyweight of more than 35 kg can be managed aggressively as adults, because they can tolerate the adult doses of anti-H. pylori therapy. In adolescents, the prevention of future peptic ulcers and gastric cancers is expected after the eradication of H. pylori. Bismuth-based quadruple therapy (bismuth-proton pump inhibitor-amoxicillin/tetracycline-metronidazole) with maximal tolerable doses and optimal dose intervals of 14 days is recommended, because in Korea, the antibiotic susceptibility test for H. pylori is not performed at the initial diagnostic evaluation. If the first-line treatment fails, concomitant therapy plus bismuth can be attempted for 14 days as an empirical rescue therapy. Finally, the salvage therapy, if needed, must be administered after the H. pylori antibiotic susceptibility test.

Keyword

Helicobacter pylori; Therapeutics; Guideline; Children

MeSH Terms

Adolescent*
Adult
Anti-Infective Agents
Bismuth
Body Weight
Child*
Diagnostic Tests, Routine
Europe
Helicobacter pylori*
Helicobacter*
Humans
Infection Control
Korea*
North America
Peptic Ulcer
Salvage Therapy
Stomach Neoplasms
Uncertainty
Anti-Infective Agents
Bismuth

Reference

1. Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ, Axon AT, et al. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017; 66:6–30.

2. Sugano K, Tack J, Kuipers EJ, Graham DY, El-Omar EM, Miura S, et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015; 64:1353–1367.

3. Kim SG, Jung HK, Lee HL, Jang JY, Lee H, Kim CG, et al. Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition. Korean J Gastroenterol. 2013; 62:3–26.

4. Jones NL, Koletzko S, Goodman K, Bontems P, Cadranel S, Casswall T, et al. Joint ESPGHAN/NASPGHAN guidelines for the management of Helicobacter pylori in children and adolescents (update 2016). J Pediatr Gastroenterol Nutr. 2017; 64:991–1003.

5. IARC Helicobacter pylori Working Group. Helicobacter pylori eradication as a strategy for preventing gastric cancer. Lyon: International Agency for Research on Cancer;2014.

6. Kato M, Ota H, Okuda M, Kikuchi S, Satoh K, Shimoyama T, et al. Guidelines for the management of Helicobacter pylori infection in Japan: 2016 revised edition. Helicobacter. 2019; 24:e12597.

7. Honma H, Nakayama Y, Kato S, Hidaka N, Kusakari M, Sado T, et al. Clinical features of Helicobacter pylori antibody-positive junior high school students in Nagano Prefecture, Japan. Helicobacter. 2019; 24:e12559.

8. Jung KW, Won YJ, Kong HJ, Lee ES. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2016. Cancer Res Treat. 2019; 51:417–430.

9. Graham DY, Lee YC, Wu MS. Rational Helicobacter pylori therapy: evidence-based medicine rather than medicine-based evidence. Clin Gastroenterol Hepatol. 2014; 12:177–186.e3. Discussion e12-3.

10. Seo J, Koo S, Youn H, Jun J, Lim J, Park C, et al. Comparison of the antibiotic resistance of Helicobacter pylori isolated in jinju over a 15-year period. J Bacteriol Virol. 2012; 42:305–312.

11. Seo JH, Jun JS, Yeom JS, Park JS, Youn HS, Ko GH, et al. Changing pattern of antibiotic resistance of Helicobacter pylori in children during 20 years in Jinju, South Korea. Pediatr Int. 2013; 55:332–336.

12. Lee JH, Ahn JY, Choi KD, Jung HY, Kim JM, Baik GH, et al. Korean College of Helicobacter. Nationwide antibiotic resistance mapping of Helicobacter pylori in Korea: a prospective multicenter study. Helicobacter. 2019; 24:e12592.

13. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017; 112:212–239.

14. Okuda M, Kikuchi S, Mabe K, Osaki T, Kamiya S, Fukuda Y, et al. Nationwide survey of Helicobacter pylori treatment for children and adolescents in Japan. Pediatr Int. 2017; 59:57–61.

15. Seo JH, Park JS, Rhee KH, Youn HS. Diagnosis of Helicobacter pylori infection in children and adolescents in Korea. Pediatr Gastroenterol Hepatol Nutr. 2018; 21:219–233.

16. Rhee KH, Youn HS, Baik SC, Lee WK, Cho MJ, Choi HJ, et al. Prevalence of Helicobacter pylori infection in Korea. J Korean Soc Microbiol. 1990; 25:475–490.

17. Borody TJ, Cole P, Noonan S, Morgan A, Lenne J, Hyland L, et al. Recurrence of duodenal ulcer and Campylobacter pylori infection after eradication. Med J Aust. 1989; 151:431–435.

18. Drumm B, Sherman P, Chiasson D, Karmali M, Cutz E. Treatment of Campylobacter pylori-associated antral gastritis in children with bismuth subsalicylate and ampicillin. J Pediatr. 1988; 113:908–912.

19. Oderda G, Vaira D, Holton J, Ainley C, Altare F, Ansaldi N. Amoxycillin plus tinidazole for Campylobacter pylori gastritis in children: assessment by serum IgG antibody, pepsinogen I, and gastrin levels. Lancet. 1989; 1:690–692.

20. Israel DM, Hassall E. Treatment and long-term follow-up of Helicobacter pylori-associated duodenal ulcer disease in children. J Pediatr. 1993; 123:53–58.

21. Park C, Choi H, Youn H, Lee W, Cho M, Kang K, et al. Chemotherapy of Helicobacter pylori infection. J Kor Soc Microbiol. 1994; 29:421–435.

22. Choi MB, Kim YO, Cho YK, Sin SK, Kim SJ, Woo HO, et al. Histopathological changes of gastroduodenal mucosa after chemotherapy of Helicobacter pylori-chronic gastritis. Korean J Gastroenterol. 1997; 29:41–52.

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

24. Bae SH, Koh JS, Seo JK. Therapeutic efficacy of dual therapy and triple therapy for Helicobacter pylori infection in children. J Korean Pediatr Soc. 1998; 41:323–330.

25. Choi J, Jang JY, Kim JS, Park HY, Choe YH, Kim KM. Efficacy of two triple eradication regimens in children with Helicobacter pylori infection. J Korean Med Sci. 2006; 21:1037–1040.

26. Hong J, Yang HR. Efficacy of proton pump inhibitor-based triple therapy and bismuth-based quadruple therapy for Helicobacter pylori eradication in Korean children. Pediatr Gastroenterol Hepatol Nutr. 2012; 15:237–242.

27. Choi IK, Lee SY, Chung KS. Effect of one- or two-week triple therapy with omeprazole, amoxicillin, and clarithromycin on eradication of Helicobacter pylori infection in children. Korean J Pediatr Gastroenterol Nutr. 2002; 5:19–25.

28. Youn JH, Kim SJ, Seo JH, Kim JY, Youn HS, Ko JS, et al. National survey assessing treatment of Helicobacter pylori infection in Korean children: a pilot study. Korean J Helicobacter Up Gastrointest Res. 2017; 17:195–199.

29. Gisbert JP, McNicholl AG. Optimization strategies aimed to increase the efficacy of H. pylori eradication therapies. Helicobacter. 2017; 22:e12392.

30. Graham DY, Dore MP. Helicobacter pylori therapy: a paradigm shift. Expert Rev Anti Infect Ther. 2016; 14:577–585.

31. Graham DY, Dore MP, Lu H. Understanding treatment guidelines with bismuth and non-bismuth quadruple Helicobacter pylori eradication therapies. Expert Rev Anti Infect Ther. 2018; 16:679–687.

32. Li H, Wang R, Sun H. Systems approaches for unveiling the mechanism of action of bismuth drugs: new medicinal applications beyond Helicobacter pylori infection. Acc Chem Res. 2019; 52:216–227.

33. Leussink BT, Slikkerveer A, Engelbrecht MR, van der Voet GB, Nouwen EJ, de Heer E, et al. Bismuth overdosing-induced reversible nephropathy in rats. Arch Toxicol. 2001; 74:745–754.

34. Youn YS, Lee KY. Mycoplasma pneumoniae pneumonia in children. Korean J Pediatr. 2012; 55:42–47.

35. Lee JW, Kim N, Kim JM, Nam RH, Chang H, Kim JY, et al. Prevalence of primary and secondary antimicrobial resistance of Helicobacter pylori in Korea from 2003 through 2012. Helicobacter. 2013; 18:206–214.

36. Choe JW, Jung SW, Kim SY, Hyun JJ, Jung YK, Koo JS, et al. Comparative study of Helicobacter pylori eradication rates of concomitant therapy vs modified quadruple therapy comprising proton-pump inhibitor, bismuth, amoxicillin, and metronidazole in Korea. Helicobacter. 2018; 23:e12466.

37. Graham DY, Lee SY. How to Effectively use bismuth quadruple therapy: the good, the bad, and the ugly. Gastroenterol Clin North Am. 2015; 44:537–563.

38. Furuta T, Sugimoto M, Yamade M, Uotani T, Sahara S, Ichikawa H, et al. Effect of dosing schemes of amoxicillin on eradication rates of Helicobacter pylori with amoxicillin-based triple therapy. J Clin Pharmacol. 2014; 54:258–266.

39. Ahn HS, Shin HY. (Hong Chang-Yee) Pediatrics. 11th ed. Seoul: MiraeN;2016. p. 554–555.

40. Lee E, Cho HJ, Hong SJ, Lee J, Sung H, Yu J. Prevalence and clinical manifestations of macrolide resistant Mycoplasma pneumoniae pneumonia in Korean children. Korean J Pediatr. 2017; 60:151–157.