• Optimizing of Sequential H. pylori Eradication Bismuth-Based Combined with an Adjuvant Therapy in Children with Chronic Gastritis

Optimizing of Sequential H. pylori Eradication Bismuth-Based Combined with an Adjuvant Therapy in Children with Chronic Gastritis

SOVREMENNAYA PEDIATRIYA.2017.4(84):101-106; doi 10.15574/SP.2017.84.101

Shevtsova O. M., Lukashuk V. D., Ali Sameh Ali, Palahniuk N. O.
Bogomolets National Medical University, Kyiv, Ukraine

Objective. To evaluate the efficacy of bismuth-based sequential anti-H. pylori therapy in children with H. pylori CagA-associated chronic gastritis.

Materials and methods. We examined eighty-three patients with chronic gastritis (the main group) aged from six to 17 years who received modified bismuth-based sequential anti-H. pylori therapy. The comparison group (n=64) was administered the 7-day bismuth-based triple therapy (n=31) and standard 7-day lansoprazole-based triple therapy (n=33). For the diagnosis of chronic gastritis, routine diagnostic procedures were performed, including tests for the detection of IgG anti-CagA antibodies in serum to define H. pylori CagA status. The serum 25-hydroxycholecalciferol (vitamin D) value was measured in all patients of the main group before the treatment: 25 children had normal vitamin D levels, and 58 ones had low vitamin D levels or its deficiency. The efficacy of the bismuth-based anti-H. pylori regimens, namely the 10-day sequential (n=83) and 7-day triple (n=31), was compared with the standard 7-day triple therapy in children with chronic gastritis. The 10-day eradication regimen comprised bismuth subcitrate + amoxicillin for the first 5 days, and bismuth subcitrate + amoxicillin + clarithromycin for the next 5 days. The 7-day triple eradication regimen included bismuth subcitrate + amoxicillin + clarithromycin. In six to eight weeks after the completion of therapy, the efficacy of H. pylori eradication was assessed using the stool antigen test.

Results. The eradication rates using the bismuth-based 10-day sequential and 7-day triple therapies were 68.7% and 83.9% respectively, and the rate of standard 7-day triple therapy made up 75.8%. Most of the patients who did not respond to the treatment were children with the vitamin D deficiency, the initially high degree of gastric mucosa colonization, and the 3-5 year duration of H. pylori infection contamination. In the main group, the rate of successful eradication in children with normal vitamin D levels was 84%, and 62.1% in children with low vitamin D levels or vitamin D deficiency. In the group of vitamin D deficiency (n=30) with administered vitamin D as an adjuvant to bismuth-based sequential anti-H. pylori therapy, the eradication rate was 70%, in group without administered an adjuvant (n=28) the eradication rate made up 53.5%.

Conclusions. Both bismuth-based 10-day sequential and 7-day triple anti-H. pylori therapies in children with H. pylori CagA-associated chronic gastritis provided a high rate of H. pylori eradication. Anti-H. pylori therapy should be carried out taking into account the patient's H. pylori CagA status and vitamin D level. In children with vitamin D deficiency, vitamin D as an adjuvant should be used along with the 10-day bismuth-based sequential anti-H. pylori therapy. The above-mentioned combination can increase the rate of successful H. pylori eradication. It is recommended to use the patient's CagA-status and vitamin D level as the additional criteria for the anti-H. pylori therapy selection.

Key words: chronic gastritis, Helicobacter pylori, sequential anti-H. pylori therapy, bismuth subcitrate, vitamin D deficiency, children.


1. Abaturov OIe, Shponka IS, Zavhorodnia NIu, Poslavska OV. (2012). Dynamika zmin stanu mistsevoho mukozalnoho zakhystu pry khronichnykh H. pylori-asotsiiovanykh hastrytakh u ditei pislia provedennia antyhelikobakternoi terapii z kholekaltsyferolom. Medychni perspektyvy. 17; 3: 101—109.

2. Isakov VA. (2006). Maastriht-3 2005: Florentiyskaya mozaika protivorechiy i kompromissov. Eksper i klin gastroenterol. 1: 78—83.

3. Maev IV, Samsonov AA, Andreev NG, Kochetov SA. (2012). Evolyutsiya predstavleniy o diagnostike i lechenii infektsii H. pylori (po materialam konsensusa Maastriht IV, Florentsiya 2010). Vestnik prakticheskogo vracha. Spetsvyip 1: 6—30.

4. Olbermann P, Josenhans C, Moodley Y et al. (2010). A global overview of the genetic and functional diversity in the H. pylori cag pathogenicity island. PLoS Genet. 16; 8: 20—30. https://doi.org/10.1371/journal.pgen.1001069

5. De Francesco V, Margiotta M, Zullo A et al. (2006).Clarithromycin!resistant genotypes and eradication of H. pylori. Ann Intern Med. 144: 94—100. https://doi.org/10.7326/0003-4819-144-2-200601170-00006; PMid:16418408

6. Malfertheiner P, Megraud F, O'Moran C et al. (2007). Current concepts in the management of H. pylori infection — The Maastricht III Consensus Report. Gut. 56: 772—781. https://doi.org/10.1136/gut.2006.101634; PMid:17170018 PMCid:PMC1954853

7. Murakami K, Fujioka T, Okimoto T et al. (2002). Drug combinations with amoxycillin reduce selection of clarithromycin resistance during H. pylori eradication therapy. Int J Antimicrob Agents. 19: 67—70. https://doi.org/10.1016/S0924-8579(01)00456-3

8. Koletzko S, Jones NL, Goodman KJ et al. (2011). Evidence-based guidelines from ESPGHAN and NASPGHAN for H. pylori infection in children. H. pylori Working Groups of ESPGHAN and NASPGHAN. J Pediatr Gastroenterol Nutr. 53(2): 230—243. PMid:21558964

9. Ge R, Chen Z, Zhou Q. (2012). The actions of bismuth in the treatment of H. pylori infections: an update. Metallomics. 4(3): 239—243. https://doi.org/10.1039/c2mt00180b; PMid:22358069

10. Gatta L, Vakil N, Vaira D, Scarpignato C. (2013). Global eradication rates for H. pylori infection: systematic review and meta-analysis of sequential therapy. BMJ. 28: 1801—1809. https://doi.org/10.1136/bmj.f4587

11. Göfcf e S. (2010). Bismuth salts in the treatment of H. pylori infection in children. Dig Dis Sei. 55(2): 53—56.

12. Scaccianoce G, Hassan C, Panarese A et al. (2006). H. pylori eradication with either 7-day or 10-day triple therapies, and with a 10-day sequential regimen. Can J Gastroenterol. 20: 113—117. https://doi.org/10.1155/2006/258768; PMid:16482238 PMCid:PMC2538976

13. Horvath A, Dziechciarz P, Szajewska H. (2013). Letter: sequential therapy for H. pylori eradication in children. Updated meta-analysis of randomized controlled trials. Aliment Pharmacol Ther. 37(8): 835—836. https://doi.org/10.1364/OL.38.005036; PMid:24281503

14. Horvath A, Dziechciarz P, Szajewska H. (2012). Meta-analysis: sequential therapy for H. pylori eradication in children. Aliment Pharmacol Ther. 36(6): 534—541. https://doi.org/10.1111/j.1365-2036.2012.05229.x; PMid:22827718

15. Francavilla R, Lionetti E, Castellaneta SP et al. (2005). Improved efficacy of 10!day sequential treatment for H. pylori eradication in children: a randomized trial. Gastroenterology. 129: 1414-1419. https://doi.org/10.1053/j.gastro.2005.09.007; PMid:16285942

16. Rick JR, Goldman M, Mora CS et al. (2010). In situ expression of cagA and risk of gastroduodenal disease in H. pylori infected children. J Pediatr Gastroenterol Nutr. 50, 2. 167—172.

17. Sugano K, Tack J, Kuipers EJ et al. (2015). Kyoto global consensus report on H. pylori gastritis. Faculty members of Kyoto Global Consensus Conference. Gut. 64(9): 1353—1367. https://doi.org/10.1136/gutjnl-2015-309252; PMid:26187502 PMCid:PMC4552923

18. Okuda M, Fukuda Y. (2009). H. pylori infection in childhood. Nihon Rinsho. 67; 12: 223—229.

19. Oderda G, Shcherbakov P, Bontems P et al. (2007, Apr). Results from the pediatric European register for treatment of H. pylori (PERTH). European Pediatric Task Force on H. pylori II Helicobacter. 12(2): 150—156.

20. Pacifico L, Osborn JF, Anania C et al. (2012, Mar 8). Review article: bismuth-based therapy for H. pylori eradication in children. Aliment Pharmacol Ther: 1010—1026. https://doi.org/10.1111/j.1365-2036.2012.05055.x

21. Gatta L, Vakil N, Leandro G et al. (2009). Sequential therapy or triple therapy for H. pylori infection: systematic review and meta-analysis of randomized controlled trials in adults and children. Am J Gastroenterol. 104(12): 3069—3079. https://doi.org/10.1038/ajg.2009.555; PMid:19844205

22. Viara D, Zullo F, Vakil N et al. (2007). Sequential therapy versus standard triple!drug therapy for H. pylori eradication: a randomized trail. Ann Int Med. 146: 556—563. https://doi.org/10.7326/0003-4819-146-8-200704170-00006

23. Bontems P, Kalach N, Oderda G et al. (2011). Sequential therapy versus tailored triple therapies for H. pylori infection in children. J Pediatr Gastroenterol Nutr Dec. 53(6): 646—650.

24. De Francesco V, Zullo A, Margiotta M et al. (2004). Sequential treatment for H. pylori does not share the risk factors of triple therapy failure. Aliment Pharmacol Ther. 19(4): 407—414. https://doi.org/10.1046/j.1365-2036.2004.01818.x; PMid:14871280

25. Zullo A, Hassan C, Ridola L et al. (2013). Standard triple and sequential therapies for H. pylori eradication: an update. Eur J Intern Med. 24(l): 16—19. https://doi.org/10.1016/j.ejim.2012.07.006; PMid:22877993

26. Zullo A, De Francesco V, Hassan C et al. (2007). The sequential therapy regimen for H. pylori eradication: a pooled-data analysis. Gut. 56(10): 1355—1357. https://doi.org/10.1136/gut.2007.125658; PMid:17566020 PMCid:PMC2000235

27. Tutar E. (2009). Endoscopic and histopathologic findings associated with H. pylori infection in very young children. Dig Dis Sci. 54(1): 111—117. https://doi.org/10.1007/s10620-008-0334-7; PMid:18594977

28. Vitoriano I. (2011). Ulcerogenic H. pylori strains isolated from children: a contribution to get insight into the virulence of the bacteria. PLoS One. 6; 10: 262—265. https://doi.org/10.1371/journal.pone.0026265; PMid:22039453 PMCid:PMC3198394

29. De Francesco V, Giorgio F, Hassan C et al. (2010). Worldwide H. pylori antibiotic resistance: a systematic review. J Gastrointestin Liver Dis. 19(4): 409—414. PMid:21188333