Resistance of helicobacter pylori to antibacterial medications as a risk factor of infection development

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UDC: 
616-08-035
DOI: 
10.21668/health.risk/2020.2.19.eng
Authors: 

M.V. Neumoina, K.M. Perfilova, N.V. Neumoina, I.V. Shutova, T.A. Troshina, T.V. Shmakova, T.L. Denisenko

Organization: 

Academician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology, 71 Malaya Yamskaya Str., Nizhny Novgorod, 603950, Russian Federation

Abstract: 

The authors have analyzed research works, both by domestic and foreign researchers that dwell on frequency of H.pylori being resistant to antibacterial medications, the reasons for its occurrence, methods applied to determine it and ways to overcome it. Over the last 15 years there has been a growth in frequency of detecting H.pylori that was resistant to basic antibiotics used to eradicate the pathogen. The authors have established geographical diversity in resistance related to antibiotics intake by population. Bacteriological technique is the most valid for determining H.pylori sensitivity; however, it is rather difficult to apply it due to complicated procedures for the microorganism cultivation. Therefore, molecular-genetic techniques are widely used. H.pylori resistance to Clarithromycin has great practical significance as this antibiotic is able not only to produce antibacterial effects but also to destroy biofilms. Helicobacter that was resistant to Clarithromycin was the least frequently detected in northern European countries (1–3%); it was the most frequently detected in Southern Europe, Asia, and South America (30–40%). Research performed in several Russian regions revealed significant variations in frequency of detecting H.pylori resistant to Clarithromycin (5–40%) and a growth in dynamics of this detection (from 5 to 15%). Frequency of detecting helicobacter resistance to another widely used medication, Metronidazole, is also different in different geographic regions; it amounts to 17% in Europe, 24% in Russia, and 92% in Africa. H.pylori still has low resistance to Amoxicillin and another reserve medication, Rifabutin.
The article also dwells on probable ways to overcome non-sensitivity of the pathogen to antibiotics and the necessity to develop procedures for treating H.pylori infection based on the results of examining the pathogen sensitivity with standardized techniques performed in different regions. Efficient H.pylori eradication reduces inflammation in the gastric mucosa, prevents ulcer formation and atrophy and reducers risks of stomach cancer.

Keywords: 
Helicobacter pylori, eradication, resistance to antibiotics, Clarithromycin, Metronidazole, Amoxicillin, Levofloxacin, Tetracycline
Neumoina M.V., Perfilova K.M., Neumoina N.V., Shutova I.V., Troshina T.A., Shmakova T.V., Denisenko T.L. Health Risk Analysis, 2020, no. 2, pp. 175–184. DOI: 10.21668/health.risk/2020.2.19.eng
References: 
  1. Maev I.V., Samsonov A.A., Andreev D.N. Infektsiya Helicobacter pylori [Helicobacter pylori infection]. Moscow, GEOTAR-media Publ., 2016, 256 p.
  2. Lee Y.C., Chiang T.H., Chou C.K., Tu Y.-K., Liao W.-C., Wu M.-S., Graham D.Y. Association Between Helicobacter pylori Eradication and Gastric Cancer Incidence: a Systematic Review and Meta-analysis. Gastroenterology, 2016, vol. 150, no. 5, pp. 113–1124. DOI: 10.1053/j.gastro.2016.01.028
  3. Malfertheiner P. Helicobacter pylori treatment for gastric cancer prevention. N Engl J Med, 2018, vol. 22, no. 378 (12), pp. 1154–1156. DOI: 10.1056/NEJMe1800147
  4. Amieva M., Peek R.M. Pathobiology of Helicobacter pylori-Induced Gastric Cancer. Gastroenterology, 2016, vol. 150, no. 1, pp. 64–78. DOI: 10.1053/j.gastro.2015.09.004
  5. Sugano K., Tack J., Kuipers J.E., Graham D.Y., El-Omar E.M., Miura S., Haruma K., Asaka M. Kyoto global consensus report on Helicobacter pylori gastritis. Gut, 2015, vol. 64, no. 9, pp. 1353–1367. DOI: 10.1136/gutjnl-2015-309252
  6. Maev I.V., Kucheryavyi Yu.A., Andreev D.N., Barkalova E.V. Eradication therapy for Helicobacter pylori infection: Review of world trends. Terapevticheskii arkhiv, 2014, no. 3, pp. 94–99 (in Russian).
  7. Malfertheiner Р., Venerito М., Schulz С. Helicobacter pylori infection: new facts in clinical management. Current Treatment Options in Gastroenterology, 2018, vol. 16, no. 4, pp. 605–615. DOI: 10.1007/s11938-018-0209-8
  8. Dekhnich N.N., Kostyakova E.A., Punin A.A., Alimov A.V., Ivanchik N.V., Kozlov R.S. Antibiotikorezistentnost' H.pylori: rezul'taty mikrobiologicheskogo regional'nogo issledovaniya [H.pylori resistance to antibiotics: results of regional microbiological research]. Rossiiskii zhurnal gastroenterologii, gepatologii, koloproktologii, 2011, no. 21 (2), pp. 37–42 (in Russian).
  9. Isaeva G.Sh. Antimicrobial Resistance of H. pylori and Susceptibility Determination Methods. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya, 2010, vol. 12, no. 1, pp. 57–66 (in Russian).
  10. Tsukanov V.V., Kasparov E.V., Vasyutin A.V., Tonkikh Yu.L. Eradication of Helicobacter Pylori. Meditsinskii sovet, 2015, no. 13, pp. 26–28 (in Russian).
  11. Megraud F., Coenen S., Versporten A., Kist M., Lopez-Brea M., Hirschl A.M., Andersen L.P., Goossens H., Glupczynski Y. Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut, 2013, vol. 62, no. 1, pp. 34–42. DOI: 10.1136/gutjnl-2012-302254
  12. Malfertheiner P., Megraud F., O’Morain С.А., Atherton J., Axon A.T., Bazzoli F., Gensini G.F., Gisbert J.P. [et al.]. Management of Helicobacter pylori infection – the Maastricht IV/Florence Consensus Report. Gut, 2012, vol. 61, no. 5, pp. 646–664. DOI: 10.1136/gutjnl-2012-302084
  13. Malfertheiner P., Megraud F., O’Morain С.А., Gisbert J.P., Kuipers E.J., Axon A.T., Bazzoli F., Gasbarrini A. [et al.]. Management of Helicobacter pylori infection – the Maastricht V/Florence Consensus Report. Gut, 2017, vol. 66, no. 1, pp. 6–30. DOI: 10.1136/gutjnl-2016-312288
  14. Sablin O.A., Mikhailov N.V., Yurin M.V., Il'chishina T.A., Kondrashin A.S., Kobiashvili M.G., Mikhailova I.A., Svarval' A.V., Zhibrun A.B. Helicobacter pylori primary resistance to antibiotics in St Petersburg. Eksperimental'naya i klinicheskaya gastroenterologiya, 2012, no. 8, pp. 18–23 (in Russian).
  15. Akhmetova D.G., Baltabekova A.Zh., Shustov A.V. Antibiotic resistance of Helicobacter pylori: review of epidemiological trends and problems of treatment. RMZh. Meditsinskoe obozrenie, 2018, no. 7 (1), pp. 13–18 (in Russian).
  16. Chey W.D., Lontiadis G.I., Howden C.W., Moss S.F. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol, vol. 112, no. 2, pp. 212–239.DOI: 10.1038/ajg.2016.563
  17. Nazarov V.E. Prichiny bezuspeshnosti eradikatsionnoi terapii, ne svyazannye s antibiotikorezistentnost'yu Helicobacter pylori, i puti ikh preodoleniya [Reasons for unsuccessful eradication therapy that are not related to Helicobacter pylori being resistant to antibiotics and ways to overcome them]. RMZh. Meditsinskoe obozrenie, 2018, no. 3, pp. 4–12 (in Russian).
  18. Uspenskii Yu.P., Baryshnikova N.V. Optimizatsiya lecheniya zabolevanii, assotsiirovannykh s infektsiei H.pylori, s uchetom sovremennykh rekomendatsii [How to optimize treatment of diseases associated with H.pylori infection taking into account up-to-date recommendations]. Aktual'nye voprosy ozdorovleniya detei i podrostkov s pomoshch'yu statsionarzameshchayushchikh tekhnologii: sbornik statei, Sankt-Peterburg, 2016, pp. 37–48 (in Russian).
  19. Simanenkov V.I., Zakharova N.V., Zhebrun A.V., Svarval' A.V., Savilova I.V., Ferman R.S. Rezistentnost' Helicobacter pylori k antimikrobnym preparatam po rezul'tatam bakteriologicheskogo testirovaniya [Helicobacter pylori resistance to antimicrobial medications as per results of bacteriological testing]. Lechashchii vrach, 2015, no. 4, pp. 91–95 (in Russian).
  20. The European Committee on Antimicrobial susceptibility Testing. Eucast. Available at: http://www.eucast.org (07.02.2020).
  21. Tsimmerman Ya.S. The problem of growing resistance of microorganisms to antibiotic therapy and prospects for helicobacter pylori eradication. Nereshennye i spornye problem sovremennoi gastroenterologii. Moscow, MEDpress-inform Publ., 2013, pp. 147–166 (in Russian).
  22. De Francesco V., Ierardi E., Hassan C., Zullo A. Helicobacter pylori therapy: present and future. World. J. Gastrointest. Pharmacol. Therapy, 2012, no. 3 (4), pp. 68–73. DOI: 10.4292/wjgpt.v3.i4.68
  23. De Francesco V., Zullo A., Hassan C., Giorgio F., Rosania R., Ierardi E. Mechanisms of Helicobacter pylori antibiotic resistance: an updated appraisal. World. J. Gastrointest. Pathophysiol, 2011, no. 2 (3), pp. 35–41. DOI: 10.4291/wjgp.v2.i3.35
  24. Megraud F. H.pylori antibiotic resistance: prevalence, importance, and advances in testing. Gut, 2004, vol. 53, no. 9, pp. 1374–1384. DOI: 10.1136/gut.2003.022111
  25. Garrido L., Toledo H. Novel genotypes in Helicobacter pylori involving domain V of the 23S rRNAgene. Helicobacter, 2007, no. 5, pp. 505–509. DOI: 10.1111/j.1523-5378.2007.00506.x
  26. Sablin O.A., Il'chishina T.A. Problema rezistentnosti Helicobacter pylori k klaritromitsinu [An issue related to Helicobacter pylori being resistant to Clarithromycin]. Gastroenterologiya, 2009, no. 2, pp. 4–8 (in Russian).
  27. Kucheryavyi Yu.A., Andreev D.N., Barkalova E.V. Сlinical and molecular aspects of helicobacter pylori resistance to antimicrobial drugs. Meditsinskii sovet, 2013, no. 10, pp. 11–15 (in Russian).
  28. Mеgraud F., Ducournau A., Bеnеjat E., Sifre E. Surveillance of Helicobacter pylori resistance to antibiotics in France in 2014. Helicobacter, 2016, vol. 21, pp. 110–114.
  29. Gatta C., Scarpignato C., Fiorini G., Belsey J., Saracino I.M., Ricci C., Vaira D. Impact of Primary Antibiotic Resistance on the Effectiveness of Sequential Therapy for Helicobacter Pylori Infection. Lessons From a 5-year Study on a Large Number of Strains. Aliment Pharmacol Ther, 2018, vol. 47, no. 9, pp. 1261–1269. DOI: 10.1111/apt.14597
  30. Parra-Sepulveda C., Merino J.S., Saez-Carrilo K., Gonzalez C., Garcia-Cancino A. Antibiotic resistance surveillance of Helicobacter pylori at the Biobio region (Chile) in a decade. Arq. Gastroenterol, 2019, vol. 56, no. 4, pp. 361–366. DOI: 10.1590/S0004-2803.201900000-72
  31. Toracchio S., Aceto G., Mariani-Costantini R., Battista P., Marzio L. Identification of a novel mutation affecting domain V of the 23S rRNA gene in Helicobacter pylori. Helicobacter, 2004, vol. 9, no. 5, pp. 396–399. DOI: 10.1111/j.1083-4389.2004.00267.x
  32. Kim J.M., Kim J.S., Kim N., Kim Y.-J., Kim I.Y., Chee Y.J., Lee C.-H., Jung H.C. Gene mutations of 23S rRNA associated with clarithromycin resistance in Helicobacter pylori strains isolated from Korean patiens. J. Microbiol. Biotechnol, 2008, vol. 18, no. 9, pp. 1584–1589.
  33. Janssen M., Hendrikse L., De Boer S., Bosboom R., De Boer W.A., Laheij R.J., Jansen J.B. Helicobacter pylori antibiotic resistance in a Dutch region: trends over time. Neth. J. Med, 2006, vol. 64, no. 6, pp. 191–195.
  34. Koivisto T., Rautelin T., Voutilainen M., Niemelä S.E., Heikkinen M., Sipponen P.I., Färkkilä M.A. Primary Helicobacter pylori resistance to metronidazole and clarithromycin in the Finnish population. Aliment. Pharmacol. Ther, 2005, vol. 19, no. 9, pp. 1009–1017. DOI: 10.1111/j.1365-2036.2004.01930.x
  35. Hooi J.K.Y., Lai W.Y., Ng W.K., Suen M.M.Y., Underwood F.E., Tanyingoh D., Malfertheiner P., Graham D.Y. [et al.]. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology, 2017, vol. 153, no. 2, pp. 420–429. DOI: 10.1053/j.gastro.2017.04.022
  36. Mabe K., Kikuchi S., Okuda M., Takamasa M., Kato M., Asaka M. Diagnostic accuracy of urine Helicobacter pylori antibody test in junior and senior high school students in Japan. Helicobacter, 2016, vol. 21, pp. 78–92. DOI: 10.1111/hel.12329
  37. Karimov M.M., Sobirova G.N., Saatov Z.Z., Islamova Sh.Z., Rustamova S.T. Prevalence and Molecular-Genetic Characteristics of Helicobacter pylori in Uzbekistan. Effektivnaya farmakoterapiya, 2019, vol. 15, no. 28, pp. 48–51 (in Russian).
  38. Megraud F. European survey of Helicobacter pylori primary resistance to antibiotics – Evolution over the last 20 years. United European Gastroenterology. Available at: http://www.ueg.eu (23.10.2019).
  39. Graham D.Y., Fischbach L. Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut, 2010, vol. 59, no. 8, pp. 1143–1153. DOI: 10.1136/gut.2009.192757
  40. Venneman K., Huybrechts I., Gunter M.J., Vandendaele L., Herrero R., Van Herck K. The epidemiology of Helicobacter pylori infection in Europe and the impact of lifestyle on its natural evolution toward stomach cancer after infection: a systematic review. Helicobacter, 2018, vol. 23, no. 3, pp. e12483. DOI: 10.1111/hel.12483
  41. Ivashkin V.T., Maev I.V., Lapina T.L., Sheptulin A.A., Trukhmanov A.S., Baranskaya E.K., Abdulkhakov R.A., Alekseeva O.P. [et al.]. Diagnostics and treatment of Helicobacter pylori infection in adults: Clinical guidelines of the Russian gastroenterological association. Rossiiskii zhurnal gastroenterologii, gepatologii, koloproktologii, 2018, vol. 28, no. 1, pp. 55–70 (in Russian).
  42. Lazebnik L.B., Belousova N.L., Bordin D.S., Mikheeva O.M., Dubtsova E.A., Vorob'eva N.N., Zelenikin S.A. Resistance of Helicobacter pylori to clarithromycin in Moscow. Propolis as a means of ienhancing the eradication effectiveness. Eksperimental'naya i klinicheskaya gastroenterologiya, 2012, no. 8, pp. 10–14 (in Russian).
  43. Baryshnikova N.V., Denisova E.V., Kornienko E.A. Epidemiologicheskoe issledovanie rezistentnosti Helicobacter pylori k klaritromitsinu u zhitelei Sankt-Peterburga s yazvennoi bolezn'yu [Epidemiologic research on Helicobacter pylori resistance to Clarithromycin among Saint Petersburg population with stomach ulcer]. Eksperimental'naya i klinicheskaya gastroenterologiya, 2009, no. 5, pp. 73–76 (in Russian).
  44. Dekhnich N., Ivanchik N., Kozlov R., Alimov A., Steshits A., Kirsov P., Pandav K. Dynamics of antimicrobial resistance of Helicobacter pylori isolates in the Smolensk region of Russian Federation. Helicobacter, 2018, vol. 23, no. 6, pp. e12545. DOI: 10.1111/hel.12545
  45. Perfilova K.M., Neumoina N.V., Shutova I.V., Neumoina M.V., Butina T.Yu., Troshina T.A., Larionova T.V., Efimova E.I. Dinamika pervichnoi i vtorichnoi rezistentnosti H.pylori k makrolidam v Nizhnem Novgorode [Dynamics of the primary and secondary H.pylori resistance to macrolides in Nizhniy Novgorod]. Rossiiskii zhurnal gastroenterologii, gepatologii, koloproktologii, 2016, vol. 26, no. 5, pp. 26 (in Russian).
  46. Abdulkhakov R.A., Abuzarova E.R., Abdulkhakov S.R., Safin A.G., Saifutdinov I.M., Chernov V.M. Resistance helicobacter pylori to clarithromycin in Kazan. Eksperimental'naya i klinicheskaya gastroenterologiya, 2012, no. 8, pp. 24–29 (in Russian).
  47. Osipenko M.F., Bikbulatova E.A., Shakalite Yu.D., Chernova L.N. Resistance to helicobacter pylori to clarithromycin in Novosibirsk. Rossiiskii zhurnal gastroenterologii, gepatologii, koloproktologii, 2012, no. 22 (5), pp. 36 (in Russian).
  48. Jaka H., Rhee J.A., Östlundh L., Smart L., Peck R., Mueller A., Kasang C., Mshana S.E. The magnitude of antibiotic resistance to Helicobacter pylori in Africa and identified mutations which confer resistance to antibiotics: systematic review and meta-analysis. BMC Infect Dis, 2018, vol. 18, no. 1, pp. 193–199. DOI: 10.1186/s12879-018-3099-4
  49. Mahachai V., Vilaichone R., Pittayanon R., Rojborwonwitaya J., Leelakusolvong S., Maneerattanaporn M., Chotivitayatarakorn P., Treeprasertsuk S. Helicobacter pylori management in ASEAN: The Bangkok consensus report. Focus on clinical aspects of H.pylori infection in Asia and recommendations for clinical management. J Gastroenterol Hepatol, 2018, vol. 33, no. 1, pp. 37–56. DOI: org/10.1111/jgh.13911
  50. Siavoshi F., Saniee P., Malekzadeh R. Effective antimicrobial activity of rifabutin against multidrug – resistant Helicobacter pylori. Helicobacter, 2018, vol. 23, no. 6, pp. e12531. DOI:10.1111/hel.12531
Received: 
05.05.2020
Accepted: 
09.06.2020
Published: 
28.06.2020

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