Preview

Experimental and Clinical Gastroenterology

Advanced search

Treatment of Helicobacter pylori infection for medical professionals

https://doi.org/10.31146/1682-8658-ecg-211-3-28-40

Abstract

Objective. To study the frequency of the presence of Helicobacter pylori (HP), the effectiveness of eradication treatment, the factors that determine the failure of treatment among doctors in Chita. Material and methods. The study involved 164 people aged 19 to 73 years (average age 45.34 ± 13.15 years), including 93 doctors and 71 patients not related to medical activities. The presence of HP infection in 112 people was investigated by determining the antigen (AH) in the feces. 98 people were examined for the presence of HP DNA in gastric biopsies and A2142G, A2143G, and T2717C mutations in the bacterial genome, providing its resistance to clarithromycin by PCR. 59 doctors performed eradication treatment for HP with different schemes. Control of eradication was carried out 6-8 weeks after the end of therapy by determining AH HP in feces. Genetic testing was carried out in 30 doctors for the carriage of polymorphic genes CYP2C19 * 2: G681A (P227P), CYP2C19 * 3: G636A (W212X), CYP2C19 * 17: C-806T, MDR1 (ABCB1: C3435T) by PCR and the effect of the revealed genetic characteristics on the results of treatment. Statistical processing was carried out using descriptive statistics, x2 test and Fisher’s test for small samples (Biostatistics software). Results. A positive AH of HP in feces was registered in 62.5% of the examined: 66.3% of doctors and 50% in the compared population (p = 0.187). HP DNA in the gastric mucosa was detected in 49 people, which was 50% of the examined people. HP DNA was detected in 73.8% of doctors and in 32.1% of non-medical workers (p < 0.001). Subject to the treatment regimen, the effectiveness of all eradication regimens was 72.5% (regimens with clarithromycin - 72.7%, with josamycin - 100%, with tetracycline and metronidazole - 43%, with levofloxacin - 85.7%). Non-compliance with the therapy regimen was noted in 8 people. The effectiveness in this group was 12.5% (p≤0.01). Mutations in the HP genome, providing resistance to clarithromycin, were found in 38.8%: in the group of doctors - 45.2%, in non-medical workers - 27.8% (p = 0.368). In the absence of genotypic resistance, effective eradication took place in 42.1%, in the presence of resistant strains - in 16.7% (p = 0.364). When genotyping CYP2C19, ultrarapid (UM) and rapid metabolizer (RM) accounted for 30%, normal - 46.7%, intermediate - 20% and poor metabolizers (PM) - 3.3%. The effectiveness of all eradication regimens among UM and RM was 55.5%, the clarithromycin regimen - 16.7% (p > 0.05). In the CT and TT MDR1 mutant alleles, the effectiveness of all eradication schemes was 69.2% - 70%, of the clarithromycin scheme - 37.5% (p> 0.05). Conclusion. Doctors are at risk for Helicobacter pylori infection. In doctors, the infection is determined 1.3-2.3 times more often (when examined by different methods) than in patients not associated with medical activities. The effectiveness of all eradication schemes was 72.5%. The worst results were demonstrated by the scheme with tetracycline and metronidazole (43%). In case of non-adherence to the therapy regimen, the probability of successful treatment was reduced by 5.8 times. There is a tendency to a decrease in the level of eradication with genotypic resistance to clarithromycin in the genome of Helicobacter pylori, in carriers of mutant alleles with UM and RM of CYP2C19 and in the TT MDR1 genotype. The revealed reasons for the ineffectiveness of HP eradication in the doctors of Chita did not differ from the general population. The exception was the genotypic resistance of Helicobacter pylori to clarithromycin, which tended to develop more frequently in doctors.

About the Authors

E. V. Luzina
Chita State Medical Academy of the Ministry of Health of Russia
Russian Federation


A. A. Dutova
Chita State Medical Academy of the Ministry of Health of Russia
Russian Federation


L. B. Lazebnik
A. I. Yevdokimov Moscow State University of Medicine and Dentistry
Russian Federation


N. V. Lareva
Chita State Medical Academy of the Ministry of Health of Russia
Russian Federation


References

1. Warren J.R., Marshall B. J. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. 1983 Jun 4;1(8336):1273-5.

2. Graham D. Y. History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer. World J. Gastroenterol. 2014;20(18):5191-5204.

3. Hooi J.K.Y., Lai W. Y., Ng W. K., Suen M. M.Y., Underwood F. E., Tanyingoh D. et al. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology. 2017 Aug;153(2):420-429.

4. Plavnik R., Nevmerzhitskiy V., Embutniex Yu., Voynovan I., Kondrasheva E., Abdulova M., Bordin D. The prevalence of Helicobacter pylori in Russia. Helicobacter. 2018;23(S1):24.

5. Peters C., Schablon A., Harling M., Wohlert C., Torres Costa J., Nienhaus A. The occupational risk of infection among gastroenterologists and their assistants. BMC Infect Dis. 2011; 11: 154.

6. KimS.Y., Chung J. W. Best Eradication Strategyinthe Era of Antibiotic Resistance. Antibiotics (Basel). 2020 Aug; 9(8): 436. Published online 2020 Jul 23. doi: 10.3390/antibiotics9080436.

7. Nyssen O.P., Bordin D., Tepes B., Pérez-Aisa A., Vaira D., Caldas M. et al. European Registry on management (Hp-EuReg): patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients. Gut. 2021 Jan;70(1):40-54. doi: 10.1136/gutjnl-2020-321372. Epub 2020 Sep 21.

8. Mayev I.V., Andreyev D. N., Bordin D.S, Kucheryavy Yu. A., Kudryavtseva L. V., Vyuchnova Ye.S. et al. Helicobacter pylori Resistance to Clarithromycin in the Russian Federation. Effective pharmacotherapy. 2020;16(30):16-22. (in Russ.) doi: 10.33978/2307-3586-2020-16-30-16-22.@@ Маев И. В., Андреев Д. Н., Бордин Д. С., Кучерявый Ю. А., Кудрявцева Л. В., Вьючнова Е. С. и др. Резистентность Helicobacter pylori к кларитромицину в Российской Федерации. Эффективная фармакотерапия. 2020; 16(30): 16-22. DOI 10.33978/2307-3586-2020-16-30-16-22.

9. Ivashkin V.T., Mayev I. V., Lapina T. L., Sheptulin A. A., Trukhmanov A. S., Baranskaya Ye.K. et al. Diagnostics and treatment of Helicobacter pylori infection in adults: Clinical guidelines of the Russian gastroenterological association. Ross z gastroenterol gepatol koloproktol. 2018; 28(1):55-70. (in Russ.) DOI: 10.22416/1382-4376-2018-28-1-55-70.@@ Ивашкин В. Т., Маев И. В., Лапина Т. Л., Шептулин А. А., Трухманов А. С., Баранская Е. К. и др. Клинические рекомендации Российской га-строэнтерологической ассоциации по диагностике и лечению инфекции Helicobacter pylori у взрослых. Рос журн гастроэнтерол гепатол колопроктол. 2018; 28(1):55-70. DOI: 10.22416/1382-4376-2018-28-1-55-70.

10. Tang H.-L., Li Y., Hu Y.-F., Xie Y.-G., Suo-Di Zhai S.-D. Effects of Loss-of-Function Variants on the Eradication of Infection in Patients Treated with Proton Pump Inhibitor-Based Triple Therapy Regimens: A Meta-Analysis of Randomized Clinical Trials. PLoS One. 2013; 8(4): e62162. Published online 2013 Apr 30. doi: 10.1371/journal.pone.0062162.

11. Bordin D. S., Plavnik R. G., Nevmerzhitskiy V. I., Butorova L. I., Abdulkhakov R. A., Abdulkhakov S. R. et al. Prevalence of Helicobacter pylori among medical workers in Moscow and Kazan according to ¹³С-urease breath test. Almanac of Clinical Medicine. 2018;46(1): 40-49. (in Russ.). doi: 10.18786/2072-0505-2018-46-1-40-49.@@ Бордин Д. С., Плавник Р. Г., Невмержицкий В. И., Буторова Л. И., Аб-дулхаков Р.А., Абдулхаков С. Р. и др. Распространенность Helicobacter pylori среди медицинских работников Москвы и Казани по данным 13С-уреазного дыхательного теста. Альманах клинической медицины. 2018; 46(1): 40-49. doi: 10.18786/2072-0505-2018-46-1-40-49.

12. Bakulina N. V., Simanenkov V. I., Bakulin I. G., Ilchishina T. A. Prevalence of Helicobacter pylori infection among physicians. Experimental and Clinical Gastroenterology. 2017;(12):20-24. (in Russ.).@@ Бакулина Н. В., Симаненков В. И., Бакулин И. Г., Ильчишина Т. А. Рас-пространенность хеликобактерной инфекции среди врачей. Экспериментальная и клиническая гастроэнтерология.2017;148(12):20-24.

13. Lima J.J., Thomas C. D., Barbarino J., Desta Z., Van Driest S. L., El Rouby N. et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. Clin Pharmacol Ther. 2021 Jun;109(6):1417-1423. doi: 10.1002/cpt.2015. Epub 2020 Sep 20.

14. Miernyk K.M., Bulkow L. R., Gold B. D., Bruce M. G., Hurlburt D. H., Griffin P. M. et al. Prevalence of Helicobacter pylori among Alaskans: Factors associated with infection and comparison of urea breath test and anti-Helicobacter pylori IgG anti-bodies. Helicobacter. 2018 Jun;23(3): e12482. doi: 10.1111/hel.12482. Epub 2018 Mar 14.

15. Melese A., Genet Ch., Zeleke B., Andualem T. Helicobacter pylori infections in Ethiopia; prevalence and associated factors: a systematic review and meta-analysis. BMC Gastroenterol. 2019 Jan 10;19(1):8. doi: 10.1186/s12876-018-0927-3.

16. Kheyre H., Morais S., Ferro A., Costa A. R., Norton P., Lunet N., Peleteiro B. The occupational risk of Helicobacter pylori infection: a systematic review.Int Arch Occup Environ Health. 2018 Aug; 91(6): 657-674. Doi: 10.1007/s00420-018-1315-6. Epub 2018 May 29.

17. Mastromarino P., Conti C., Donato K., Strappini P. M., Cattaruzza M. S., Orsi G. B. Does hospital work constitute a risk factor for Helicobacter pylori infection? The Journal Hospital Infecion. 2005;60(3):261-268.

18. Leja M., Grinberga-Derica I., Bilgilier C., Steininger C. Review: Epidemiology of Helicobacter pylori infection. Helicobacter. 2019 Sep;24 Suppl 1: e12635. https//doi.org/10.1111/hel.12635.

19. Hildebrand P., Meyer-Wyss B.M., Mossi S., Beglinger C. Risk among gastroenterologists of acquiring Helicobacter pylori infection: case control study. BMJ. 2000 Jul 15; 321(7254): 149. doi: 10.1136/bmj.321.7254.149.

20. Lazebnik L. B., Tkachenko E. I., Abdulganiyeva D. I., Abdulkhakov R. A., et al. VI National guidelines for the diagnosis and treatment of acid-related and Helicobacter pylori-associated diseases (VI Moscow agreement). Experimental and Clinical Gastroenterology. 2017;(2):3-21. (in Russ.)@@ Лазебник Л. Б., Ткаченко Е. И., Абдулганиева Д. И., Абдулхаков Р. А. и др. VI Национальные рекомендации по диагностике и лечению кислотозависимых и ассоциированных с Helicobacter pylori заболеваний (VI Московские соглашения). Экспериментальная и клиническая гастроэнтерология. 2017;138(02):3-21.

21. Bordin D. S., Embutnieks Yu.V., Vologzhanina L. G., Ilchishina T. A., Voynovan I. N., et al. European registry Helicobacter pylori (Hp- EuReg): how has clinical practice changed in Russia from 2013 to 2018 years. Therapeutic Archive. 2019;91(2):16-24 (in Russ.) doi: 10.26442/ 00403660.2019.02.000156.@@ Бордин Д. С., Эмбутниекс Ю. В., Вологжанина Л. Г., Ильчишина Т. А., Войнован И. Н., Сарсенбаева А. С. и др. Европейский регистр Helicobacter pylori (Hp-EuReg): как изменилась клиническая практика в России с 2013 по 2018 г. Терапевтический архив. 2019; 2: 16-24. doi: 10.26442/00403660.2019.02.000156

22. Bordin D. S., Voynovan I. N., Embutnieks Yu.V., et al. European registry on Helicobacter pylori management (Hp-EuReg) as a tool to evaluate and improve clinical practice in Moscow. Therapeutic Archive. 2020; 92 (2):12-18 (in Russ.). doi: 10.26442/00403660.2020.02.000567.@@ Бордин Д. С., Войнован И. Н., Эмбутниекс Ю. В. и др. Европейский регистр Helicobacter pylori (Hp-EuReg) как инструмент для оценки и улучшения клинической практики в Москве. Терапевтический архив. 2020; 92(2): 12-18. doi: 10.26442/00403660.2020.02.000567.

23. Abdulkhakov S. R., Bordin D. S., Abdulkhakov R. A., et al. European Registry on the management of Helicobacter pylori infection: features of diagnosis and treatment in Kazan. Therapeutic Archive. 2020;92(8):52-59. (in Russ.). doi: 10.26442/00403660.2020.08.000758. PMID: 33346462@@ Абдулхаков С. Р., Бордин Д. С., Абдулхаков Р. А. и др. Европейский регистр ведения инфекции Helicobacter pylori: особенности диагностики и лечения в Казани. Терапевтический архив. 2020; 92(8): 52-59. doi: 10.26442/ 00403660.2020.08.000758.

24. McNicholl A.G., Bordin D. S., Lucendo A., Fadeenko G., Fernandez M. C., Voynovan I. et al.Combination of Bismuth and Standard Triple Therapy Eradicates Helicobacter pylori Infection in More than 90% of Patients. Clin Gastroenterol Hepatol. 2020 Jan;18(1):89-98. doi: 10.1016/j.cgh.2019.03.048. Epub 2019 Apr 10.

25. Zou Y., Qian X., Liu X., Song YP., Song C., Wu Sh. et al. The effect of antibiotic resistance on Helicobacter pylori eradication efficacy: A systematic review and meta-analysis. Helicobacter. 2020 Aug;25(4): e12714. doi: 10.1111/hel.12714. Epub 2020 Jun 12.

26. Gisbert J. P. Empirical or susceptibility-guided treatment for infection? A comprehensive review. Therap Adv Gastroenterol. 2020; 13: 1756284820968736. Published online 2020 Nov 12. doi: 10.1177/1756284820968736.

27. Harris, D.M., Stancampiano, F.F., Burton, M.C., et al. Use of Pharmacogenomics to Guide Proton Pump Inhibitor Therapy in Clinical Practice. Dig Dis Sci. 66, 4120-4127 (2021). doi: 10.1007/s10620-020-06814-1.

28. Shah S.C., Tepler А., Chung С. Р., Suarez G., Peek R. M., Hung A., et al. Host Genetic Determinants Associated with Helicobacter pylori Eradication Treatment Failure: A Systematic Review and Meta-analysis. Gastroenterology. 2021 Nov;161(5):1443-1459. doi: 10.1053/j.gastro.2021.07.043. Epub 2021 Aug 3.

29. Zhang H.-J., Zhang X. H., Liu J., Sun L.-N., Chen Y. W., Zhou C. et al. Effects of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of proton pump inhibitors. Pharm. Res. 2020 Feb;152: 104606.

30. Yoon S.B., Park J. M., Lee J. Y., et al. Long-term pretreatment with proton pump inhibitor and Helicobacter pylori eradication rates. World J. Gastroenterol. 2014; 20(4): 1061-66.

31. Bakulina N. V., Maev I. V., Savilova I. V., Bakulin I. G. et al. Efficacy of Helicobacter pylori eradication depending on genetic polymorphism of CYP2C19, MDR1 and IL-1β. Therapeutic Archive, 2019;91(8):34-40. (in Russ.). DOI: 10.26442/00403660.2019.08.000380.@@ Бакулина Н. В., Маев И. В., Савилова И. В., Бакулин И. Г. и др. Эффективность эрадикации Helicobacter pylori в зависимости от генетического полиморфизма CYT2C19, MDR1 и IL-1β. Терапевтический архив. 2019; 8: 34-40. DOI: 10.26442/00403660.2019.08. 000380.

32. Elokhina E.V., Kostenko M. B., Livzan M. A., Scalskiy S. V. The effectiveness of eradication in patients with peptic ulcer disease associated with Helicobacter pylori, depending on the genotype of the drug metabolism of proton pump inhibitors. Experimental and Clinical Gastroenterology. 2015; 115(3):31-33. (in Russ.)@@ Елохина Е. В., Костенко М. Б., Ливзан М. А., Скальский С. В. Эффективность эрадикационной терапии у пациентов с язвенной болезнью, ассоциированной с Helicobacter pylori, в зависимости от генотипа лекарственного метаболизма ингибиторов протонной помпы. Экспериментальная и клиническая гастроэнтерология. 2015; 115(3): 31-33.

33. Maev I.V., Belyj P. A., Lebedeva E. G. Influence of CYP2C19 gene poly-morphism on the effectiveness of using proton pump inhibitors in the treatment of gastroesophageal reflux disease. Lechashchij vrach. 2011; 7: 93-95. (in Russ.)@@ Маев И. В., Белый П. А., Лебедева Е. Г. Влияние полиморфизма гена CYP2C19 на эффективность использования ингибиторов протонной помпы в лечении гастроэзофагеальной рефлюксной болезни. Лечащий врач. 2011; 7: 93-95.

34. Sugimoto M., Furuta T. Efficacy of tailored Helicobacter pylori eradication therapy based on antibiotic susceptibility and CYP2C19 genotype. World J Gastroenterol. 2014 Jun 7; 20(21): 6400-6411. doi: 10.3748/wjg.v20.i21.6400.

35. Shi C, Lixian W. Influence of MDR1 C3435T polymorphism on the eradication of Helicobacter pylori in patiens with gastric ulcer. Chin J Gerontol. 2014;34:6955-6956.

36. Yakusheva E.N., Shulkin A. V., Popova N. M., Chernyh I. V., Titov D. S. Structure, functions of P-glycoprotein and its role in rational pharmacotherapy. Reviews on clinical pharmacology and drug therapy. 2014; 12(2): 3-11. (in Russ.)@@ Якушева Е. Н., Щулькин А. В., Попова Н. М., Черных И. В., Титов Д. С. Структура, функции гликопротеина-Р и его значение для рациональной фармакотерапии. Обзоры по клинической фармакологии и лекарственной терапии. 2014; 12(2): 3-11.

37. Auttajaroon J., Chotivitayatarakorn P., Yamaoka Y., Vilaichone R.-K. CYP2C19 Genotype, CagA Genotype and Antibiotic Resistant Strain of Helicobacter pylori Infection. Asian Pac J Cancer Prev. 2019; 20(4): 1243-1247 doi: 10.31557/APJCP.2019.20.4.1243.

38. Song Y., Dou F., Zhou Z., Yang N., Zhong J., Pan J., et al. Microarray-Based Detection and Clinical Evaluation for Resistance to Clarithromycin or Levofloxacin and the Genotype of CYP2C19 in 1083 Patients. Biomed Res Int. 2018; 2018: 2684836. Published online 2018 Sep 10. doi: 10.1155/2018/2684836.

39. Furuta T., Sugimoto M., Shirai N., Matsushita F., Nakajima H., Kumagai J. Effect of MDR1 C3435T polymorphism on cure rates of Helicobacter pylori infection by triple therapy with lansoprazole, amoxicillin and clarithromycin in relation to CYP 2C19 genotypes and 23S rRNA genotypes of H. pylori. Aliment Pharmacol Ther. 2007 Sep 1;26(5):693-703. doi: 10.1111/j.1365-2036.2007.03408.x.


Review

For citations:


Luzina E.V., Dutova A.A., Lazebnik L.B., Lareva N.V. Treatment of Helicobacter pylori infection for medical professionals. Experimental and Clinical Gastroenterology. 2023;(3):28-40. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-211-3-28-40

Views: 302


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1682-8658 (Print)