medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2026-217medsovet-10202Research ArticleЗАБОЛЕВАНИЯ ПИЩЕВОДА И ЖЕЛУДКАESOPHAGEAL AND GASTRIC DISEASESСовременные возможности тройной фармакотерапии инфекции Helicobacter pyloriCurrent potential for Helicobacter pylori triple pharmacotherapyhttps://orcid.org/0000-0002-7163-7119СереброваС. Ю.SerebrovaS. Yu.

Сереброва Светлана Юрьевна - д.м.н., ведущий научный сотрудник, Научный центр экспертизы средств медицинского применения; профессор кафедры клинической фармакологии и пропедевтики внутренних болезней, Первый МГМУ имени И.М. Сеченова (Сеченовский Университет).

127051, Москва, Петровский бульвар, д. 8, стр. 2; 119048, Москва, ул. Трубецкая, д. 8, стр. 2

Svetlana Yu. Serebrova - Dr. Sci. (Med.), Chief Scientific Researcher, Scientific Centre for Expert Evaluation of Medicinal Products; Professor of Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Sechenov FMSMU (Sechenov University);

8, Bldg. 2, Petrovsky Boulevard, Moscow, 127051; 8, Bldg. 2, Trubetskaya St., Moscow, 119048

serebrova@expmed.ruhttps://orcid.org/0000-0003-1972-4386ЕсаковаЕ. Ю.EsakovaE. Yu.

Есакова Елена Юрьевна - к.фарм.н., ведущий аналитик Научного отдела клинической фармакологии, Научный центр экспертизы средств медицинского применения; ассистент кафедры клинической фармакологии и пропедевтики внутренних болезней, Первый МГМУ имени И.М. Сеченова (Сеченовский Университет).

127051, Москва, Петровский бульвар, д. 8, стр. 2; 119048, Москва, ул. Трубецкая, д. 8, стр. 2

Elena Yu. Esakova - Cand. Sci. (Med.), Leading Analyst, Scientific Centre for Expert Evaluation of Medicinal Products; Assistant Professor of Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Sechenov FMSMU (Sechenov University).

8, Bldg. 2, Petrovsky Boulevard, Moscow, 127051; 8, Bldg. 2, Trubetskaya St., Moscow, 119048

demchenkova@expmed.ruhttps://orcid.org/0000-0001-6528-1585ЛазареваН. Б.LazarevaN. B.

Лазарева Наталья Борисовна - д.м.н., профессор кафедры клинической фармакологии и пропедевтики внутренних болезней.

119048, Москва, ул. Трубецкая, д. 8, стр. 2

Natalia B. Lazareva - Dr. Sci. (Med.), Professor of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases.

8, Bldg. 2, Trubetskaya St., Moscow, 119048

lazareva_n_b@staff.sechenov.ruhttps://orcid.org/0000-0002-7322-3323ГородецкаяГ. И.GorodetskayaG. I.

Городецкая Галина Ивановна - ассистент кафедры клинической фармакологии и пропедевтики внутренних болезней.

119048, Москва, ул. Трубецкая, д. 8, стр. 2

Galina I. Gorodetskaya - Assistant Professor of Department of Clinical Pharmacology and Propaedeutics of Internal Diseases.

8, Bldg. 2, Trubetskaya St., Moscow, 119048

ggorodetskaya@bk.ruhttps://orcid.org/0009-0003-5251-5348ДобровольскийО. В.DobrovolskyO. V.

Добровольский Олег Викторович - к.м.н., заведующий отделением эндоскопии.

125367, Москва, Иваньковское шоссе, д. 7

Oleg V. Dobrovolsky - Cand. Sci. (Med.), Head of the Endoscopy Department.

Ivankovskoe Shosse, Moscow, 125367

ov_dobrovolsky@mail.ruhttps://orcid.org/0000-0002-9198-8661ЖуравлеваМ. В.ZhuravlevaM. V.

Журавлева Марина Владимировна - д.м.н., заместитель начальника Научного отдела клинической фармакологии, Научный центр экспертизы средств медицинского применения; профессор кафедры клинической фармакологии и пропедевтики внутренних болезней, Первый МГМУ имени И.М. Сеченова (Сеченовский Университет).

127051, Москва, Петровский бульвар, д. 8, стр. 2; 119048, Москва, ул. Трубецкая, д. 8, стр. 2

Marina V. Zhuravleva - Dr. Sci. (Med.), Deputy Head of the Scientific Department of Clinical Pharmacology, Scientific Centre for Expert Evaluation of Medicinal Products; Professor of Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Sechenov FMSMU (Sechenov University).

8, Bldg. 2, Petrovsky Boulevard, Moscow, 127051; 8, Bldg. 2, Trubetskaya St., Moscow, 119048

zhuravleva@expmed.ruhttps://orcid.org/0000-0001-7024-5546ПрокофьевА. Б.ProkofievA. B.

Прокофьев Алексей Борисович - д.м.н., профессор, начальник Научного отдела клинической фармакологии, Научный центр экспертизы средств медицинского применения; профессор кафедры клинической фармакологии и пропедевтики внутренних болезней, Первый МГМУ имени И.М. Сеченова (Сеченовский Университет).

127051, Москва, Петровский бульвар, д. 8, стр. 2; 119048, Москва, ул. Трубецкая, д. 8, стр. 2

Alexey B. Prokofiev - Dr. Sci. (Med.), Professor, Head of the Scientific Department of Clinical Pharmacology, Scientific Centre for Expert Evaluation of Medicinal Products; Professor of Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Sechenov FMSMU (Sechenov University).

8, Bldg. 2, Petrovsky Boulevard, Moscow, 127051; 8, Bldg. 2, Trubetskaya St., Moscow, 119048

prokofiev@expmed.ruНаучный центр экспертизы средств медицинского применения; Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)РоссияScientific Centre for Expert Evaluation of Medicinal Products; Sechenov First Moscow State Medical University (Sechenov University)Russian FederationПервый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)РоссияSechenov First Moscow State Medical University (Sechenov University)Russian FederationЦентральная клиническая больница гражданской авиацииРоссияCentral Clinical Hospital of Civil AviationRussian Federation202601072026082235Copyright © Сереброва С.Ю., Есакова Е.Ю., Лазарева Н.Б., Городецкая Г.И., Добровольский О.В., Журавлева М.В., Прокофьев А.Б., 20262026Сереброва С.Ю., Есакова Е.Ю., Лазарева Н.Б., Городецкая Г.И., Добровольский О.В., Журавлева М.В., Прокофьев А.Б.Serebrova S.Y., Esakova E.Y., Lazareva N.B., Gorodetskaya G.I., Dobrovolsky O.V., Zhuravleva M.V., Prokofiev A.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/10202

Инфекция Helicobacter pylori представляет глобальную проблему здравоохранения, поскольку патоген ассоциирована с развитием язвенной болезни желудка и двенадцатиперстной кишки, гастритом, аденокарциномой желудка и MALT-лимфомой. Эффективность эрадикационной терапии снижается вследствие нарастающей антибиотикорезистентности, что требует пересмотра терапевтических стратегий. В статье представлены механизмы выживания H. pylori в агрессивной среде желудка, его факторы патогенности, современные данные о механизмах действия основных антибактериальных препаратов, применяемых при лечении инфекции в России и мире: кларитромицина, метронидазола, амоксициллина, тетрациклина, левофлоксацина, рифабутина, висмута трикалия дицитрата, а также механизмы формирования резистентности для них. Детально рассмотрены однофазные и двухфазные схемы эрадикационной терапии согласно российским клиническим рекомендациям 2022 г. и консенсусу Маастрихт VI, включая схемы первой линии: стандартную тройную терапию, усиленную и неусиленную препаратами висмута, конкоминантную, последовательную, гибридную, обратную гибридную, квадротерапию с препаратами висмута, двойную высокодозовую, вонопразановую двойную терапию. Для терапии второй линии рассмотрены схемы, включающие левофлоксацин, рифабутин, изложены принципы индивидуализированной терапии. Дана краткая клинико-фармакологическая характеристика каждого препарата. Также проанализированы причины неудач в поиске оптимальной схемы эрадикации H. pylori. Упомянуто изменение отношения Всемирной организации здравоохранения к H. pylori как к возбудителю, требующему разработки новых антибактериальных препаратов. Рассмотрены понятия «постантибиотическая эра» и «ренессанс антибиотиков». В заключительной части рассмотрены риски, связанные с выбором схемы терапии первой линии и препаратов, входящих в них. Сделано заключение, что при надлежащей оценке резистентности H. pylori тройная фармакотерапия с висмутом или без него является сравнительно эффективной и безопасной схемой эрадикации для регионов Российской Федерации. Учет особенностей метаболизма кларитромицина, нежелательных лекарственных реакций препаратов позволяет сделать рациональный выбор терапии первой линии, учитывающей физиологические и клинические особенности пациентов с инфекцией H. pylori.

Helicobacter pylori infection represents a global public health problem, as the pathogen is associated with the development of gastric and duodenal ulcer disease, gastritis, gastric adenocarcinoma, and MALT lymphoma. The efficacy of eradication therapy is declining due to increasing antibiotic resistance, necessitating a revision of therapeutic strategies. The article presents the mechanisms of H. pylori survival in the aggressive gastric environment, its pathogenicity factors, current data on the mechanisms of action of the main antibacterial drugs used for treating the infection in Russia and worldwide: clarithromycin, metronidazole, amoxicillin, tetracycline, levofloxacin, rifabutin, bismuth tripotassium dicitrate, as well as the mechanisms of resistance development for these agents. Single-phase and two-phase eradication therapy regimens are examined in detail according to the 2022 Russian clinical guidelines and the Maastricht VI consensus, including first-line regimens: standard triple therapy, bismuth-enhanced and non-bismuth-enhanced, concomitant, sequential, hybrid, reverse hybrid, bismuth-based quadruple therapy, high-dose dual therapy, and vonoprazan-based dual therapy. For second-line therapy, regimens including levofloxacin and rifabutin are reviewed, and the principles of individualized therapy are outlined. A brief clinical and pharmacological characterization of each drug is provided. The reasons for failures in finding the optimal H. pylori eradication regimen are also analyzed. The World Health Organization's changing stance toward H. pylori as a pathogen requiring the development of new antibacterial drugs is mentioned. The concepts of the "post-antibiotic era" and the renaissance of antibiotics are discussed. The concluding section examines the risks associated with the choice of first-line therapy regimens and the drugs included in them. It is concluded that with proper assessment of H. pylori resistance, triple pharmacotherapy with or without bismuth is a relatively effective and safe eradication regimen for regions of the Russian Federation. Consideration of clarithromycin metabolism characteristics and adverse drug reactions allows for rational selection of first-line therapy that accounts for the physiological and clinical features of patients with H. pylori infection.

Helicobacter pyloriэрадикационная терапиятройная стандартная терапиякларитромицинамоксициллинвисмута трикалия дицитратрезистентность к кларитромицинуHelicobacter pylorieradication therapystandard triple therapyclarithromycinamoxicillinbismuth tripotassium dicitrateresistance for clarithromycinReferencesVan Der Weyden MB, Armstrong RM, Gregory AT. The 2005 Nobel Prize in physiology or medicine. Med J Aust. 2005;183(11-12):612–614. https://doi.org/10.5694/j.1326-5377.2005.tb00052.x.Van Der Weyden MB, Armstrong RM, Gregory AT. The 2005 Nobel Prize in physiology or medicine. Med J Aust. 2005;183(11-12):612–614. https://doi.org/10.5694/j.1326-5377.2005.tb00052.x.Бордин ДС, Шенгелия МИ, Иванова ВА, Войнован ИН. История открытия бактерии Helicobacter pylori. Терапевтический архив. 2022;94(2):283–288. https://doi.org/10.26442/00403660.2022.02.201377.Bordin DS, Shengelia MI, Ivanova VA, Voynovan IN. The history of the discovery of the Helicobacter pylori. Terapevticheskii Arkhiv. 2022;94(2):283–288. (In Russ.) https://doi.org/10.26442/00403660.2022.02.201377.Lazarate Cuba RJ, Quigley EM. A History of the Discovery of Helicobacter Pylori, with Special Reference to Giulio Bizzozero. J Gastrointestin Liver Dis. 2024;33(4):535–541. https://doi.org/10.15403/jgld-5942.Lazarate Cuba RJ, Quigley EM. A History of the Discovery of Helicobacter Pylori, with Special Reference to Giulio Bizzozero. J Gastrointestin Liver Dis. 2024;33(4):535–541. https://doi.org/10.15403/jgld-5942.Pincock S. Nobel Prize winners Robin Warren and Barry Marshall. Lancet. 2005;366(9495):1429. https://doi.org/10.1016/S0140-6736(05)67587-3.Pincock S. Nobel Prize winners Robin Warren and Barry Marshall. Lancet. 2005;366(9495):1429. https://doi.org/10.1016/S0140-6736(05)67587-3.Andreev DN, Khurmatullina AR, Maev IV, Bordin DS, Abdulkhakov SR, Kucheryavyy YA et al. The Prevalence of Helicobacter pylori Infection in the Adult Population of Russia: A Systematic Review and Meta-Analysis. Epidemiologia. 2025;6(3):47. https://doi.org/10.3390/epidemiologia6030047.Andreev DN, Khurmatullina AR, Maev IV, Bordin DS, Abdulkhakov SR, Kucheryavyy YA et al. The Prevalence of Helicobacter pylori Infection in the Adult Population of Russia: A Systematic Review and Meta-Analysis. Epidemiologia. 2025;6(3):47. https://doi.org/10.3390/epidemiologia6030047.Андреев ДН, Хурматуллина АР, Бордин ДС, Маев ИВ. Динамика распространенности инфекции Helicobacter pylori у взрослого населения Москвы: систематический обзор и метаанализ. Терапевтический архив. 2025;97(5):463–470. https://doi.org/10.26442/00403660.2025.05.203250.Andreev DN, Khurmatullina AR, Bordin DS, Maev IV. Trends in the prevalence of Helicobacter pylori infection among adults in Moscow: a systematic review and meta-analysis. Terapevticheskii Arkhiv. 2025;97(5):463–470. (In Russ.) https://doi.org/10.26442/00403660.2025.05.203250.Бакулина НВ, Тихонов СВ, Савилова ИВ, Жарков АВ, Пономаренко ВА. Динамика распространенности инфекции Helicobacter pylori с 2015 по 2023 годы. Вестник Северо­Западного государственного медицинского университета им. И.И. Мечникова. 2023;15(3):41–51. https://doi.org/10.17816/mechnikov623259.Bakulina NV, Tikhonov SV, Savilova IV, Zharkov AV, Ponomarenko VA. Dynamics of the prevalence of Helicobacter pylori infection from 2015 to 2023. Herald of North­Western State Medical University named after I.I. Mechnikov. 2023;15(3):41–51. (In Russ.) https://doi.org/10.17816/mechnikov623259.Wroblewski LE, Peek RM Jr, Wilson KT. Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev. 2010;23(4):713–739. https://doi.org/10.1128/CMR.00011-10.Wroblewski LE, Peek RM Jr, Wilson KT. Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev. 2010;23(4):713–739. https://doi.org/10.1128/CMR.00011-10.Chen YC, Malfertheiner P, Yu HT, Kuo CL, Chang YY, Meng FT et al. Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022. Gastroenterology. 2024;166(4):605–619. https://doi.org/10.1053/j.gastro.2023.12.022.Chen YC, Malfertheiner P, Yu HT, Kuo CL, Chang YY, Meng FT et al. Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022. Gastroenterology. 2024;166(4):605–619. https://doi.org/10.1053/j.gastro.2023.12.022.Tempera PJ, Michael M, Tageldin O, Hasak S. Gastric Cancer Due to Chronic H. pylori Infection: What We Know and Where We Are Going. Diseases. 2022;10(3):57. https://doi.org/10.3390/diseases10030057.Tempera PJ, Michael M, Tageldin O, Hasak S. Gastric Cancer Due to Chronic H. pylori Infection: What We Know and Where We Are Going. Diseases. 2022;10(3):57. https://doi.org/10.3390/diseases10030057.Gravina AG, Zagari RM, De Musis C, Romano L, Loguercio C, Romano M. Helicobacter pylori and extragastric diseases: A review. World J Gastroenterol. 2018;24(29):3204–3221. https://doi.org/10.3748/wjg.v24.i29.3204.Gravina AG, Zagari RM, De Musis C, Romano L, Loguercio C, Romano M. Helicobacter pylori and extragastric diseases: A review. World J Gastroenterol. 2018;24(29):3204–3221. https://doi.org/10.3748/wjg.v24.i29.3204.Pădureanu V, Dop D, Caragea DC, Rădulescu D, Pădureanu R, Forțofoiu MC. Cardiovascular and Neurological Diseases and Association with Helicobacter Pylori Infection-An Overview. Diagnostics. 2024;14(16):1781. https://doi.org/10.3390/diagnostics14161781.Pădureanu V, Dop D, Caragea DC, Rădulescu D, Pădureanu R, Forțofoiu MC. Cardiovascular and Neurological Diseases and Association with Helicobacter Pylori Infection-An Overview. Diagnostics. 2024;14(16):1781. https://doi.org/10.3390/diagnostics14161781.Aksoy H, Sebin SO. H. pylori and Cardiovascular Diseases. General Medicine. 2015;(Suppl. 1):1–6. https://doi.org/10.4172/2327-5146.1000S1-007.Aksoy H, Sebin SO. H. pylori and Cardiovascular Diseases. General Medicine. 2015;(Suppl. 1):1–6. https://doi.org/10.4172/2327-5146.1000S1-007.Du J, Shen W, Zhou Z, Wu Q, Ai Z. Association of Helicobacter pylori infection with the risk of neurodegenerative disorders: a systematic review and meta-analysis. Front Med. 2025;12:1573299. https://doi.org/10.3389/fmed.2025.1573299.Du J, Shen W, Zhou Z, Wu Q, Ai Z. Association of Helicobacter pylori infection with the risk of neurodegenerative disorders: a systematic review and meta-analysis. Front Med. 2025;12:1573299. https://doi.org/10.3389/fmed.2025.1573299.Alvarez-Arellano L, Maldonado-Bernal C. Helicobacter pylori and neurological diseases: Married by the laws of inflammation. World J Gastrointest Pathophysiol. 2014;5(4):400–404. https://doi.org/10.4291/wjgp.v5.i4.400.Alvarez-Arellano L, Maldonado-Bernal C. Helicobacter pylori and neurological diseases: Married by the laws of inflammation. World J Gastrointest Pathophysiol. 2014;5(4):400–404. https://doi.org/10.4291/wjgp.v5.i4.400.Ansari S, Yamaoka Y. Survival of Helicobacter pylori in gastric acidic territory. Helicobacter. 2017;22(4):10.1111/hel.12386. https://doi.org/10.1111/hel.12386.Ansari S, Yamaoka Y. Survival of Helicobacter pylori in gastric acidic territory. Helicobacter. 2017;22(4):10.1111/hel.12386. https://doi.org/10.1111/hel.12386.Dunn BE, Phadnis SH. Structure, function and localization of Helicobacter pylori urease. Yale J Biol Med. 1998;71(2):63–73. https://pubmed.ncbi.nlm.nih.gov/10378351.Dunn BE, Phadnis SH. Structure, function and localization of Helicobacter pylori urease. Yale J Biol Med. 1998;71(2):63–73. https://pubmed.ncbi.nlm. nih.gov/10378351.Weeks DL, Eskandari S, Scott DR, Sachs G. A H+-Gated Urea Channel: The Link Between Helicobacter pylori Urease and Gastric Colonization. Science. 2000;287(5452):482–485. https://doi.org/10.1126/science.287.5452.482.Weeks DL, Eskandari S, Scott DR, Sachs G. A H+-Gated Urea Channel: The Link Between Helicobacter pylori Urease and Gastric Colonization. Science. 2000;287(5452):482–485. https://doi.org/10.1126/science.287.5452.482.Gu H. Role of Flagella in the Pathogenesis of Helicobacter pylori. Curr Microbiol. 2017;74(7):863–869. https://doi.org/10.1007/s00284-017-1256-4.Gu H. Role of Flagella in the Pathogenesis of Helicobacter pylori. Curr Microbiol. 2017;74(7):863–869. https://doi.org/10.1007/s00284-017-1256-4.You S, Li J, Chua EG, Tay A, Benghezal M, Marshall B et al. Helicobacter pylori outer membrane protein families and related pathogenesis. Microb Pathog. 2025;206:107740. https://doi.org/10.1016/j.micpath.2025.107740.You S, Li J, Chua EG, Tay A, Benghezal M, Marshall B et al. Helicobacter pylori outer membrane protein families and related pathogenesis. Microb Pathog. 2025;206:107740. https://doi.org/10.1016/j.micpath.2025.107740.Sedarat Z, Taylor-Robinson AW. Helicobacter pylori Outer Membrane Proteins and Virulence Factors: Potential Targets for Novel Therapies and Vaccines. Pathogens. 2024;13(5):392. https://doi.org/10.3390/pathogens13050392.Sedarat Z, Taylor-Robinson AW. Helicobacter pylori Outer Membrane Proteins and Virulence Factors: Potential Targets for Novel Therapies and Vaccines. Pathogens. 2024;13(5):392. https://doi.org/10.3390/pathogens13050392.Chmiela M, Kupcinskas J. Review: Pathogenesis of Helicobacter pylori infection. Helicobacter. 2019;24(Suppl. 1):e12638. https://doi.org/10.1111/hel.12638.Chmiela M, Kupcinskas J. Review: Pathogenesis of Helicobacter pylori infection. Helicobacter. 2019;24(Suppl. 1):e12638. https://doi.org/10.1111/hel.12638.Chung JM, Sheedlo MJ, Campbell AM, Sawhney N, Frick-Cheng AE, Lacy DB et al. Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 2019;8:e47644. https://doi.org/10.7554/eLife.47644.Chung JM, Sheedlo MJ, Campbell AM, Sawhney N, Frick-Cheng AE, Lacy DB et al. Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 2019;8:e47644. https://doi.org/10.7554/eLife.47644.Takahashi-Kanemitsu A, Knight CT, Hatakeyama M. Molecular anatomy and pathogenic actions of Helicobacter pylori CagA that underpin gastric carcinogenesis. Cell Mol Immunol. 2020;17:50–63. https://doi.org/10.1038/s41423-019-0339-5.Takahashi-Kanemitsu A, Knight CT, Hatakeyama M. Molecular anatomy and pathogenic actions of Helicobacter pylori CagA that underpin gastric carcinogenesis. Cell Mol Immunol. 2020;17:50–63. https://doi.org/10.1038/s41423-019-0339-5.Shuman JHB, Lin AS, Westland MD, Bryant KN, Fortier GE, Piazuelo MB et al. Helicobacter pylori CagA and Cag type IV secretion system activity have key roles in triggering gastric transcriptional and proteomic alterations. Infect Immun. 2025;93(4):e0059524. https://doi.org/10.1128/iai.00595-24.Shuman JHB, Lin AS, Westland MD, Bryant KN, Fortier GE, Piazuelo MB et al. Helicobacter pylori CagA and Cag type IV secretion system activity have key roles in triggering gastric transcriptional and proteomic alterations. Infect Immun. 2025;93(4):e0059524. https://doi.org/10.1128/iai.00595-24.Jain P, Luo ZQ, Blanke SR. Helicobacter pylori vacuolating cytotoxin A (VacA) engages the mitochondrial fission machinery to induce host cell death. Proc Natl Acad Sci U S A. 2011;108(38):16032–16037. https://doi.org/10.1073/pnas.1105175108.Jain P, Luo ZQ, Blanke SR. Helicobacter pylori vacuolating cytotoxin A (VacA) engages the mitochondrial fission machinery to induce host cell death. Proc Natl Acad Sci U S A. 2011;108(38):16032–16037. https://doi.org/10.1073/pnas.1105175108.Brasil-Costa I, Souza CO, Monteiro LCR, Santos MES, Oliveira EHC, Burbano RMR. H. pylori Infection and Virulence Factors cagA and vacA (s and m Regions) in Gastric Adenocarcinoma from Pará State, Brazil. Pathogens. 2022;11(4):414. https://doi.org/10.3390/pathogens11040414.Brasil-Costa I, Souza CO, Monteiro LCR, Santos MES, Oliveira EHC, Burbano RMR. H. pylori Infection and Virulence Factors cagA and vacA (s and m Regions) in Gastric Adenocarcinoma from Pará State, Brazil. Pathogens. 2022;11(4):414. https://doi.org/10.3390/pathogens11040414.Sijmons D, Guy AJ, Walduck AK, Ramsland PA. Helicobacter pylori and the Role of Lipopolysaccharide Variation in Innate Immune Evasion. Front Immunol. 2022;13:868225. https://doi.org/10.3389/fimmu.2022.868225.Sijmons D, Guy AJ, Walduck AK, Ramsland PA. Helicobacter pylori and the Role of Lipopolysaccharide Variation in Innate Immune Evasion. Front Immunol. 2022;13:868225. https://doi.org/10.3389/fimmu.2022.868225.Yonezawa H, Osaki T, Kamiya S. Biofilm Formation by Helicobacter pylori and Its Involvement for Antibiotic Resistance. Biomed Res Int. 2015;2015:914791. https://doi.org/10.1155/2015/914791.Yonezawa H, Osaki T, Kamiya S. Biofilm Formation by Helicobacter pylori and Its Involvement for Antibiotic Resistance. Biomed Res Int. 2015;2015:914791. https://doi.org/10.1155/2015/914791.Tao W, Ma W, Zhao G, Zhang Z, Xu C, Wang P, Jia W. Characterization of antibiotic resistance and biofilm formation in clinical Helicobacter pylori isolates from Ningxia, China. Sci Rep. 2025;15:45439. https://doi.org/10.1038/s41598-025-29451-y.Tao W, Ma W, Zhao G, Zhang Z, Xu C, Wang P, Jia W. Characterization of antibiotic resistance and biofilm formation in clinical Helicobacter pylori isolates from Ningxia, China. Sci Rep. 2025;15:45439. https://doi.org/10.1038/s41598-025-29451-y.Wei S, Li X, Wang J, Wang Ya. Outer Membrane Vesicles Secreted by Helicobacter pylori Transmitting Gastric Pathogenic Virulence Factors. ACS Omega. 2022;7(1):240–258. https://doi.org/10.1021/acsomega.1c04549.Wei S, Li X, Wang J, Wang Ya. Outer Membrane Vesicles Secreted by Helicobacter pylori Transmitting Gastric Pathogenic Virulence Factors. ACS Omega. 2022;7(1):240–258. https://doi.org/10.1021/acsomega.1c04549.Suerbaum S, Smith JM, Bapumia K, Morelli G, Smith NH, Kunstmann E et al. Free recombination within Helicobacter pylori. Proc Natl Acad Sci U S A. 1998;95(21):12619–12624. https://doi.org/10.1073/pnas.95.21.12619.Suerbaum S, Smith JM, Bapumia K, Morelli G, Smith NH, Kunstmann E et al. Free recombination within Helicobacter pylori. Proc Natl Acad Sci U S A. 1998;95(21):12619–12624. https://doi.org/10.1073/pnas.95.21.12619.Mazaheri Assadi M, Chamanrokh P, Whitehouse CA, Huq A. Methods for Detecting the Environmental Coccoid Form of Helicobacter pylori. Front Public Health. 2015;3:147. https://doi.org/10.3389/fpubh.2015.00147.Mazaheri Assadi M, Chamanrokh P, Whitehouse CA, Huq A. Methods for Detecting the Environmental Coccoid Form of Helicobacter pylori. Front Public Health. 2015;3:147. https://doi.org/10.3389/fpubh.2015.00147.Ивашкин ВТ, Лапина ТЛ, Маев ИВ, Драпкина ОМ, Козлов РС, Шептулин АА и др. Клинические рекомендации Российской гастроэнтерологической ассоциации, Научного сообщества по содействию клиническому изучению микробиома человека, Российского общества профилактики неинфекционных заболеваний, Межрегиональной ассоциации по клинической микробиологии и антимикробной химиотерапии по диагностике и лечению H. pylori у взрослых. Российский журнал гастро­энтерологии, гепатологии, колопроктологии. 2022;32(6):72–93. https://doi.org/10.22416/1382-4376-2022-32-6-72-93.Ivashkin VT, Lapina TL, Maev IV, Drapkina OM, Kozlov RS, Sheptulin AA et al. Clinical Practice Guidelines of Russian Gastroenterological Association, Scientific Society for the Clinical Study of Human Microbiome, Russian Society for the Prevention of Non-Communicable Diseases, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy for H. pylori Diagnostics and Treatment in Adults. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2022;32(6):72–93. (In Russ.) https://doi.org/10.22416/1382-4376-2022-32-6-72-93.Zhou BG, Mei YZ, Jiang X, Zheng AJ, Ding YB. Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication: A systematic review and meta-analysis of randomized controlled trials. Saudi J Gastroenterol. 2023;29(6):347–357. https://doi.org/10.4103/sjg.sjg_153_23.Zhou BG, Mei YZ, Jiang X, Zheng AJ, Ding YB. Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication: A systematic review and metaanalysis of randomized controlled trials. Saudi J Gastroenterol. 2023;29(6):347–357. https://doi.org/10.4103/sjg.sjg_153_23.Paul R, Postius S, Melchers K, Schäfer KP. Mutations of the Helicobacter pylori genes rdxA and pbp1 cause resistance against metronidazole and amoxicillin. Antimicrob Agents Chemother. 2001;45(3):962–965. https://doi.org/10.1128/AAC.45.3.962-965.2001.Paul R, Postius S, Melchers K, Schäfer KP. Mutations of the Helicobacter pylori genes rdxA and pbp1 cause resistance against metronidazole and amoxicillin. Antimicrob Agents Chemother. 2001;45(3):962–965. https://doi.org/10.1128/AAC.45.3.962-965.2001.Qureshi NN, Gallaher B, Schiller NL. Evolution of amoxicillin resistance of Helicobacter pylori in vitro: characterization of resistance mechanisms. Microb Drug Resist. 2014;20(6):509-516. https://doi.org/10.1089/mdr.2014.0019.Qureshi NN, Gallaher B, Schiller NL. Evolution of amoxicillin resistance of Helicobacter pylori in vitro: characterization of resistance mechanisms. Microb Drug Resist. 2014;20(6):509-516. https://doi.org/10.1089/mdr.2014.0019.Schulz C, Liou JM, Alboraie M, Bornschein J, Campos Nunez C, Coelho LG et al. Helicobacter pylori antibiotic resistance: a global challenge in search of solutions. Gut. 2025;74(10):1561–1570. https://doi.org/10.1136/gutjnl2025-335523.Schulz C, Liou JM, Alboraie M, Bornschein J, Campos Nunez C, Coelho LG et al. Helicobacter pylori antibiotic resistance: a global challenge in search of solutions. Gut. 2025;74(10):1561–1570. https://doi.org/10.1136/gutjnl2025-335523.Маев ИВ, Андреев ДН, Фоменко АК, Подпорин МС, Лямина СВ, Заборовский АВ и др. Динамика антибиотикорезистентности инфекции Helicobacter pylori в Москве. Терапевтический архив. 2025;97(2):163–168. https://doi.org/10.26442/00403660.2025.02.203193.Maev IV, Andreev DN, Fomenko AK, Podporin MS, Lyamina SV, Zaborovsky AV et al. Trends of antibiotic resistance of Helicobacter pylori in Moscow. Terapevticheskii Arkhiv. 2025;97(2):163–168. (In Russ.) https://doi.org/10.26442/00403660.2025.02.203193.Andreev DN, Khurmatullina AR, Maev IV, Bordin DS, Zaborovskiy AV, Abdulkhakov SR et al. Helicobacter pylori Antibiotic Resistance in Russia: A Systematic Review and Meta-Analysis. Antibiotics. 2025;14(5):524. https://doi.org/10.3390/antibiotics14050524.Andreev DN, Khurmatullina AR, Maev IV, Bordin DS, Zaborovskiy AV, Abdulkhakov SR et al. Helicobacter pylori Antibiotic Resistance in Russia: A Systematic Review and Meta-Analysis. Antibiotics. 2025;14(5):524. https://doi.org/10.3390/antibiotics14050524.Ribeiro ML, Vitiello L, Miranda MC, Benvengo YH, Godoy AP, Mendonca S, Pedrazzoli JJr. Mutations in the 23S rRNA gene are associated with clarithromycin resistance in Helicobacter pylori isolates in Brazil. Ann Clin Microbiol Antimicrob. 2003;2:11. https://doi.org/10.1186/1476-0711-2-11.Ribeiro ML, Vitiello L, Miranda MC, Benvengo YH, Godoy AP, Mendonca S, Pedrazzoli JJr. Mutations in the 23S rRNA gene are associated with clarithromycin resistance in Helicobacter pylori isolates in Brazil. Ann Clin Microbiol Antimicrob. 2003;2:11. https://doi.org/10.1186/1476-0711-2-11.Лапина ТЛ. Значение кларитромицина в эрадикационной терапии инфекции Helicobacter pylori. Consilium Medicum. 2010;12(8):14–18. Режим доступа: https://consilium.orscience.ru/2075-1753/article/view/93192.Lapina TL. The value of clarithromycin in eradication therapy of Helicobacter pylori infection. Consilium Medicum. 2010;12(8):14–18. (In Russ.) Available at: https://consilium.orscience.ru/2075-1753/article/view/93192.Дехнич НН. Роль кларитромицина в тройной терапии Н. Pylori-инфекции. Вестник Смоленской государственной медицинской академии. 2010;(1):68–73. Режим доступа: https://sgma.info/ru/issues-archive/20102019/2010/2010-1.html.Dekhnich NN. The role of clarithromycin in triple therapy of H. Pylori infection. Vestnik of Smolensk State Medical Academy. 2010;(1):68–73 (In Russ.) Available at: https://sgma.info/ru/issues-archive/2010-2019/2010/2010-1.html.Hussein RA, Al-Ouqaili MTS, Majeed YH. Detection of clarithromycin resistance and 23SrRNA point mutations in clinical isolates of Helicobacter pylori isolates: Phenotypic and molecular methods. Saudi J Biol Sci. 2022;29(1):513–520. https://doi.org/10.1016/j.sjbs.2021.09.024.Hussein RA, Al-Ouqaili MTS, Majeed YH. Detection of clarithromycin resistance and 23SrRNA point mutations in clinical isolates of Helicobacter pylori isolates: Phenotypic and molecular methods. Saudi J Biol Sci. 2022;29(1):513–520. https://doi.org/10.1016/j.sjbs.2021.09.024.Khademi F, Faghri J, Moghim S, Esfahani BN, Fazeli H, Poursina F et al. The study of mutation in 23S rRNA resistance gene of Helicobacter pylori to clarithromycin in patients with gastrointestinal disorders in Isfahan – Iran. Adv Biomed Res. 2014;3:98. https://doi.org/10.4103/2277-9175.129368.Khademi F, Faghri J, Moghim S, Esfahani BN, Fazeli H, Poursina F et al. The study of mutation in 23S rRNA resistance gene of Helicobacter pylori to clarithromycin in patients with gastrointestinal disorders in Isfahan – Iran. Adv Biomed Res. 2014;3:98. https://doi.org/10.4103/2277-9175.129368.Morad Kasani S, Mofid M, Navidifar T, Golab N, Parvizi E, Badmasti F et al. Insights into Helicobacter pylori macrolide resistance: a comprehensive systematic review and meta-analysis. Front Microbiol. 2024;15:1481763. https://doi.org/10.3389/fmicb.2024.1481763.Morad Kasani S, Mofid M, Navidifar T, Golab N, Parvizi E, Badmasti F et al. Insights into Helicobacter pylori macrolide resistance: a comprehensive systematic review and meta-analysis. Front Microbiol. 2024;15:1481763. https://doi.org/10.3389/fmicb.2024.1481763.Salahi-Niri A, Nabavi-Rad A, Monaghan TM, Rokkas T, Doulberis M, Sadeghi A et al. Global prevalence of Helicobacter pylori antibiotic resistance among children in the world health organization regions between 2000 and 2023: a systematic review and meta-analysis. BMC Med. 2024;22(1):598. https://doi.org/10.1186/s12916-024-03816-y.Salahi-Niri A, Nabavi-Rad A, Monaghan TM, Rokkas T, Doulberis M, Sadeghi A et al. Global prevalence of Helicobacter pylori antibiotic resistance among children in the world health organization regions between 2000 and 2023: a systematic review and meta-analysis. BMC Med. 2024;22(1):598. https://doi.org/10.1186/s12916-024-03816-y.Hong TC, El-Omar EM, Kuo YT, Wu JY, Chen MJ, Chen CC et al. Asian Pacific Alliance on Helicobacter and Microbiota. Primary antibiotic resistance of Helicobacter pylori in the Asia-Pacific region between 1990 and 2022: an updated systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2024;9(1):56–67. https://doi.org/10.1016/S2468-1253(23)00281-9.Hong TC, El-Omar EM, Kuo YT, Wu JY, Chen MJ, Chen CC et al. Asian Pacific Alliance on Helicobacter and Microbiota. Primary antibiotic resistance of Helicobacter pylori in the Asia-Pacific region between 1990 and 2022: an updated systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2024;9(1):56–67. https://doi.org/10.1016/S2468-1253(23)00281-9.Маев ИВ, Андреев ДН, Бордин ДС, Кучерявый ЮА, Кудрявцева ЛВ, Вьючнова ЕС и др. Резистентность Helicobacter pylori к кларитромицину в Российской Федерации. Эффективная фармакотерапия. 2020;16(30):16–22. https://doi.org/10.33978/2307-3586-2020-16-30-16-22.Maev IV, Andreev DN, Bordin DS, Kucheryavy YuA, Kudryavtseva LV, Vyuchnova ES et al. Helicobacter pylori Resistance to Clarithromycin in the Russian Federation. Effective Pharmacotherapy. 2020;16(30):16–22. (In Russ.) https://doi.org/10.33978/2307-3586-2020-16-30-16-22.Полякова ВВ, Бодунова НА, Цапкова ЛА, Серебряков ВВ, Никольская КА, Чеботарева МВ и др. Влияние резистентности H. pylori к кларитромицину на эффективность эрадикационной терапии первой линии: предварительные результаты проспективного исследования. Эффективная фармакотерапия. 2025;21(22):18–23. https://doi.org/10.33978/2307-3586-2025-21-22-18-23.Polyakova VV, Bodunova NA, Tsapkova LA, Serebryakov VV, Nikolskaya KA, Chebotareva MV et al. The impact of H. pylori resistance to clarithromycin on the efficacy of first-line eradication therapy: preliminary results of a prospective study. Effective Pharmacotherapy. 2025;21(22):18–23. (In Russ.) https://doi.org/10.33978/2307-3586-2025-21-22-18-23.Sisson G, Jeong JY, Goodwin A, Bryden L, Rossler N, Lim-Morrison S et al. Metronidazole activation is mutagenic and causes DNA fragmentation in Helicobacter pylori and in Escherichia coli containing a cloned H. pylori RdxA(+) (Nitroreductase) gene. J Bacteriol. 2000;182(18):5091–5096. https://doi.org/10.1128/JB.182.18.5091-5096.2000.Sisson G, Jeong JY, Goodwin A, Bryden L, Rossler N, Lim-Morrison S et al. Metronidazole activation is mutagenic and causes DNA fragmentation in Helicobacter pylori and in Escherichia coli containing a cloned H. pylori RdxA(+) (Nitroreductase) gene. J Bacteriol. 2000;182(18):5091–5096. https://doi.org/10.1128/JB.182.18.5091-5096.2000.Marques B, Donato MM, Cardoso O, Luxo C, Martinho A, Almeida N. Study of rdxA and frxA genes mutations in metronidazole-resistant and -susceptible Helicobacter pylori clinical isolates from the central region of Portugal. J Glob Antimicrob Resist. 2019;17:300–304. https://doi.org/10.1016/j.jgar.2019.01.008.Marques B, Donato MM, Cardoso O, Luxo C, Martinho A, Almeida N. Study of rdxA and frxA genes mutations in metronidazole-resistant and -susceptible Helicobacter pylori clinical isolates from the central region of Portugal. J Glob Antimicrob Resist. 2019;17:300–304. https://doi.org/10.1016/j.jgar.2019.01.008.Gong Y, Zhai K, Sun L, He L, Wang H, Guo Y, Zhang J. RdxA Diversity and Mutations Associated with Metronidazole Resistance of Helicobacter pylori. Microbiol Spectr. 2023;11(2):e0390322. https://doi.org/10.1128/spectrum.03903-22.Gong Y, Zhai K, Sun L, He L, Wang H, Guo Y, Zhang J. RdxA Diversity and Mutations Associated with Metronidazole Resistance of Helicobacter pylori. Microbiol Spectr. 2023;11(2):e0390322. https://doi.org/10.1128/spectrum.03903-22.Zhao Y, He L, Sun L, Liu W, Wang H, Zhang J et al. RdxA-independent mechanism of Helicobacter pylori metronidazole metabolism. Front Microbiol. 2025;16:1553734. https://doi.org/10.3389/fmicb.2025.1553734.Zhao Y, He L, Sun L, Liu W, Wang H, Zhang J et al. RdxA-independent mechanism of Helicobacter pylori metronidazole metabolism. Front Microbiol. 2025;16:1553734. https://doi.org/10.3389/fmicb.2025.1553734.Андреев ДН, Маев ИВ, Кучерявый ЮА. Резистентность Helicobacter pylori в Российской Федерации: метаанализ исследований за последние 10 лет. Терапевтический архив. 2020;92(11):24–30. https://doi.org/10.26442/00403660.2020.11.000795.Andreev DN, Maev IV, Kucheryavy YA. Helicobacter pylori resistance in the Russian Federation: a meta-analysis of studies over the past 10 years. Terapevticheskii Arkhiv. 2020;92(11):24–30. (In Russ.) https://doi.org/10.26442/00403660.2020.11.000795.Svensson M, Nilsson LE, Ström M, Nilsson M, Sörberg M. Pharmacodynamic effects of nitroimidazoles alone and in combination with clarithromycin on Helicobacter pylori. Antimicrob Agents Chemother. 2002;46(7):2244-8. https://doi.org/10.1128/AAC.46.7.2244-2248.2002.Svensson M, Nilsson LE, Ström M, Nilsson M, Sörberg M. Pharmacodynamic effects of nitroimidazoles alone and in combination with clarithromycin on Helicobacter pylori. Antimicrob Agents Chemother. 2002;46(7):2244-8. https://doi.org/10.1128/AAC.46.7.2244-2248.2002.Mégraud F, Hazell S, Glupczynski Y. Antibiotic Susceptibility and Resistance. In: Mobley HLT, Mendz GL, Hazell SL (eds.). Helicobacter pylori: Physiology and Genetics. Washington (DC): ASM Press; 2001. Available at: https://www.ncbi.nlm.nih.gov/books/NBK2469.Mégraud F, Hazell S, Glupczynski Y. Antibiotic Susceptibility and Resistance. In: Mobley HLT, Mendz GL, Hazell SL (eds.). Helicobacter pylori: Physiology and Genetics. Washington (DC): ASM Press; 2001. Available at: https://www.ncbi.nlm.nih.gov/books/NBK2469.Malfertheiner P, Megraud F, Rokkas T. On behalf of the European Helicobacter and Microbiota Study group, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022;71:1724–1762. https://doi.org/10.1136/gutjnl-2022-327745.Malfertheiner P, Megraud F, Rokkas T. On behalf of the European Helicobacter and Microbiota Study group, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022;71:1724–1762. https://doi.org/10.1136/gutjnl-2022-327745.Юхин ЮМ, Коледова ЕС, Логутенко ОА. Висмут и его соединения в меди­ цине. М.: РАН; 2022. 234 с. Режим доступа: http://www.issc-ras.ru/upload/iblock/012/Юхин_БЛОК_с_обложкой.pdf.Юхин ЮМ, Коледова ЕС, Логутенко ОА. Висмут и его соединения в меди­ цине. М.: РАН; 2022. 234 с. Режим доступа: http://www.issc-ras.ru/upload/iblock/012/Юхин_БЛОК_с_обложкой.pdf.Lambert JR, Midolo P. The actions of bismuth in the treatment of Helicobacter pylori infection. Aliment Pharmacol Ther. 1997;(Suppl. 1):27–33. https://doi.org/10.1046/j.1365-2036.11.s1.13.x.Lambert JR, Midolo P. The actions of bismuth in the treatment of Helicobacter pylori infection. Aliment Pharmacol Ther. 1997;(Suppl. 1):27–33. https://doi.org/10.1046/j.1365-2036.11.s1.13.x.Ge R, Chen Z, Zhou Q. The actions of bismuth in the treatment of Helicobacter pylori infections: an update. Metallomics. 2012;4(3):239–243. https://doi.org/10.1039/c2mt00180b.Ge R, Chen Z, Zhou Q. The actions of bismuth in the treatment of Helicobacter pylori infections: an update. Metallomics. 2012;4(3):239–243. https://doi.org/10.1039/c2mt00180b.Stratton CW, Warner RR, Coudron PE, Lilly NA. Bismuth-mediated disruption of the glycocalyx-cell wall of Helicobacter pylori: ultrastructural evidence for a mechanism of action for bismuth salts. J Antimicrob Chemother. 1999;43(5):659–666. https://doi.org/10.1093/jac/43.5.659.Stratton CW, Warner RR, Coudron PE, Lilly NA. Bismuth-mediated disruption of the glycocalyx-cell wall of Helicobacter pylori: ultrastructural evidence for a mechanism of action for bismuth salts. J Antimicrob Chemother. 1999;43(5):659–666. https://doi.org/10.1093/jac/43.5.659.Оковитый СВ, Ивкин ДЮ. Препараты висмута – фармакологические основы клинического эффекта. Лечащий врач. 2015;(10):67–73. Режим доступа: https://www.lvrach.ru/2015/10/15436322.Okovity SV, Ivkin DYu. Bismuth preparations – pharmacological basis of clinical effect. Lechaschi Vrach. 2015;(10):67–73. (In Russ.) Available at: https://www.lvrach.ru/2015/10/15436322.Bland MV, Ismail S, Heinemann JA, Keenan JI. The action of bismuth against Helicobacter pylori mimics but is not caused by intracellular iron deprivation. Antimicrob Agents Chemother. 2004;48(6):1983–1988. https://doi.org/10.1128/aac.48.6.1983-1988.2004.Bland MV, Ismail S, Heinemann JA, Keenan JI. The action of bismuth against Helicobacter pylori mimics but is not caused by intracellular iron deprivation. Antimicrob Agents Chemother. 2004;48(6):1983–1988. https://doi.org/10.1128/aac.48.6.1983-1988.2004.Kumar S, Schmitt C, Gorgette O, Marbouty M, Duchateau M, Giai Gianetto Q et al. Bacterial Membrane Vesicles as a Novel Strategy for Extrusion of Antimicrobial Bismuth Drug in Helicobacter pylori. mBio. 2022;13(5):e0163322. https://doi.org/10.1128/mbio.01633-22.Kumar S, Schmitt C, Gorgette O, Marbouty M, Duchateau M, Giai Gianetto Q et al. Bacterial Membrane Vesicles as a Novel Strategy for Extrusion of Antimicrobial Bismuth Drug in Helicobacter pylori. mBio. 2022;13(5):e0163322. https://doi.org/10.1128/mbio.01633-22.Reum Choe A, Tae CH, Choi M, Shim KN, Jung HK. Systematic Review and Meta-Analysis: Bismuth Enhances the Efficacy for Eradication of Helicobacter pylori. Helicobacter. 2024;29(5):e13141. https://doi.org/10.1111/hel.13141.Reum Choe A, Tae CH, Choi M, Shim KN, Jung HK. Systematic Review and Meta-Analysis: Bismuth Enhances the Efficacy for Eradication of Helicobacter pylori. Helicobacter. 2024;29(5):e13141. https://doi.org/10.1111/hel.13141.Gisbert JP, Parra P, Nyssen OP. Review Article: Classic Bismuth Quadruple Therapy for Helicobacter pylori Infection-Questions Focused on Clinical Practice. Aliment Pharmacol Ther. 2026;63(5):616–636. https://doi.org/10.1111/apt.70535.Gisbert JP, Parra P, Nyssen OP. Review Article: Classic Bismuth Quadruple Therapy for Helicobacter pylori Infection-Questions Focused on Clinical Practice. Aliment Pharmacol Ther. 2026;63(5):616–636. https://doi.org/10.1111/apt.70535.Stähler FN, Odenbreit S, Haas R, Wilrich J, Vliet AHMV, Kusters JG et al. The Novel Helicobacter pylori CznABC Metal Efflux Pump Is Required for Cadmium, Zinc, and Nickel Resistance, Urease Modulation, and Gastric Colonization. Infect Immun. 2006;74(7):3845–3852. https://doi.org/10.1128/iai.02025-05.Stähler FN, Odenbreit S, Haas R, Wilrich J, Vliet AHMV, Kusters JG et al. The Novel Helicobacter pylori CznABC Metal Efflux Pump Is Required for Cadmium, Zinc, and Nickel Resistance, Urease Modulation, and Gastric Colonization. Infect Immun. 2006;74(7):3845–3852. https://doi.org/10.1128/iai.02025-05.Sadeghloo Z, Fatemi N, Raeisi H, Azizmohammad Looha M, Sadeghi A. Coccoid H. pylori: A key driver of recurrent infections and a target for novel therapies. Virulence. 2025;16(1):2566964. https://doi.org/10.1080/21505594.2025.2566964.Sadeghloo Z, Fatemi N, Raeisi H, Azizmohammad Looha M, Sadeghi A. Coccoid H. pylori: A key driver of recurrent infections and a target for novel therapies. Virulence. 2025;16(1):2566964. https://doi.org/10.1080/21505594.2025.2566964.Zullo A, Scaccianoce G, De Francesco V, Ruggiero V, D’Ambrosio P, Castorani L et al. Concomitant, sequential, and hybrid therapy for H. pylori eradication: a pilot study. Clin Res Hepatol Gastroenterol. 2013;37(6):647–650. https://doi.org/10.1016/j.clinre.2013.04.003.Zullo A, Scaccianoce G, De Francesco V, Ruggiero V, D’Ambrosio P, Castorani L et al. Concomitant, sequential, and hybrid therapy for H. pylori eradication: a pilot study. Clin Res Hepatol Gastroenterol. 2013;37(6):647–650. https://doi.org/10.1016/j.clinre.2013.04.003.Hsu PI, Lin PC, Graham DY. Hybrid therapy for Helicobacter pylori infection: A systemic review and meta-analysis. World J Gastroenterol. 2015;21(45):12954–12962. https://doi.org/10.3748/wjg.v21.i45.12954.Hsu PI, Lin PC, Graham DY. Hybrid therapy for Helicobacter pylori infection: A systemic review and meta-analysis. World J Gastroenterol. 2015;21(45):12954–12962. https://doi.org/10.3748/wjg.v21.i45.12954.Valizadeh Toosi SM, Maleki I, Hosseini V, Shokri-Afra H. Non-inferiority of reverse hybrid regimen versus standard concomitant regimen for H. pylori eradication in a randomized-controlled trial. Caspian J Intern Med. 2023;14(4):687–693. https://doi.org/10.22088/cjim.14.4.687.Valizadeh Toosi SM, Maleki I, Hosseini V, Shokri-Afra H. Non-inferiority of reverse hybrid regimen versus standard concomitant regimen for H. pylori eradication in a randomized-controlled trial. Caspian J Intern Med. 2023;14(4):687–693. https://doi.org/10.22088/cjim.14.4.687.Hu Y, Ouyang Y, Zhu Y, Lu N-H. Reverse hybrid therapy for Helicobacter pylori eradication: A systematic review and meta-analysis. Helicobacter. 2021;26:e12784. https://doi.org/10.1111/hel.12784.Hu Y, Ouyang Y, Zhu Y, Lu N-H. Reverse hybrid therapy for Helicobacter pylori eradication: A systematic review and meta-analysis. Helicobacter. 2021;26:e12784. https://doi.org/10.1111/hel.12784.Zhu YJ, Zhang Y, Wang TY, Zhao JT, Zhao Z, Zhu JR, Lan CH. High dose PPIamoxicillin dual therapy for the treatment of Helicobacter pylori infection: a systematic review with meta-analysis. Ther Adv Gastroenterol. 2020;13:1756284820937115. https://doi.org/10.1177/1756284820937115.Zhu YJ, Zhang Y, Wang TY, Zhao JT, Zhao Z, Zhu JR, Lan CH. High dose PPIamoxicillin dual therapy for the treatment of Helicobacter pylori infection: a systematic review with meta-analysis. Ther Adv Gastroenterol. 2020;13:1756284820937115. https://doi.org/10.1177/1756284820937115.Hajiani E, Hashemi SJ, Parsi A, Seyedian SS, Ramim T, Sabbaghan A. Eradication efficacy of high-dose amoxicillin and proton pump inhibitor compared with quadruple therapy contained bismuth in the treatment of Helicobacter pylori. J Family Med Prim Care. 2022;11(12):7806–7809. https://doi.org/10.4103/jfmpc.jfmpc_1035_22.Hajiani E, Hashemi SJ, Parsi A, Seyedian SS, Ramim T, Sabbaghan A. Eradication efficacy of high-dose amoxicillin and proton pump inhibitor compared with quadruple therapy contained bismuth in the treatment of Helicobacter pylori. J Family Med Prim Care. 2022;11(12):7806–7809. https://doi.org/10.4103/jfmpc.jfmpc_1035_22.Chey WD, Mégraud F, Laine L, López LJ, Hunt BJ, Howden CW. Vonoprazan Triple and Dual Therapy for Helicobacter pylori Infection in the United States and Europe: Randomized Clinical Trial. Gastroenterology. 2022;163(3):608–619. https://doi.org/10.1053/j.gastro.2022.05.055.Chey WD, Mégraud F, Laine L, López LJ, Hunt BJ, Howden CW. Vonoprazan Triple and Dual Therapy for Helicobacter pylori Infection in the United States and Europe: Randomized Clinical Trial. Gastroenterology. 2022;163(3):608–619. https://doi.org/10.1053/j.gastro.2022.05.055.Chey WD, Howden CW, Moss SF, Morgan DR, Greer K, Grover Sh et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2024;119(9):1730–1753. https://doi.org/10.14309/ajg.0000000000002968.Chey WD, Howden CW, Moss SF, Morgan DR, Greer K, Grover Sh et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2024;119(9):1730–1753. https://doi.org/10.14309/ajg.0000000000002968.Shutter MC, Akhondi H. Tetracycline. [Updated 2023 Jun 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026. Available at: https://www.ncbi.nlm.nih.gov/books/NBK549905.Shutter MC, Akhondi H. Tetracycline. [Updated 2023 Jun 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026. Available at: https://www.ncbi.nlm.nih.gov/books/NBK549905.Connell SR, Tracz DM, Nierhaus KH, Taylor DE. Ribosomal protection proteins and their mechanism of tetracycline resistance. Antimicrob Agents Chemother. 2003;47(12):3675–3681. https://doi.org/10.1128/AAC.47.12.3675-3681.2003.Connell SR, Tracz DM, Nierhaus KH, Taylor DE. Ribosomal protection proteins and their mechanism of tetracycline resistance. Antimicrob Agents Chemother. 2003;47(12):3675–3681. https://doi.org/10.1128/AAC.47.12.3675-3681.2003.Trieber CA, Taylor DE. Mutations in the 16S rRNA genes of Helicobacter pylori mediate resistance to tetracycline. J Bacteriol. 2002;184(8):2131–2140. https://doi.org/10.1128/JB.184.8.2131-2140.2002.Trieber CA, Taylor DE. Mutations in the 16S rRNA genes of Helicobacter pylori mediate resistance to tetracycline. J Bacteriol. 2002;184(8):2131–2140. https://doi.org/10.1128/JB.184.8.2131-2140.2002.Wu JY, Kim JJ, Reddy R, Wang WM, Graham DY, Kwon DH. Tetracyclineresistant clinical Helicobacter pylori isolates with and without mutations in 16S rRNA-encoding genes. Antimicrob Agents Chemother. 2005;49(2):578–583. https://doi.org/10.1128/AAC.49.2.578-583.2005.Wu JY, Kim JJ, Reddy R, Wang WM, Graham DY, Kwon DH. Tetracyclineresistant clinical Helicobacter pylori isolates with and without mutations in 16S rRNA-encoding genes. Antimicrob Agents Chemother. 2005;49(2):578–583. https://doi.org/10.1128/AAC.49.2.578-583.2005.Menbari S, Shahsavar SK, Keikha M, Karbalaei M. Global Profile of Drug Resistance Related to Helicobacter pylori Infection in Children: A Systematic Review and Meta-Analysis. Health Sci Rep. 2025;8(9):e71238. https://doi.org/10.1002/hsr2.71238.Menbari S, Shahsavar SK, Keikha M, Karbalaei M. Global Profile of Drug Resistance Related to Helicobacter pylori Infection in Children: A Systematic Review and Meta-Analysis. Health Sci Rep. 2025;8(9):e71238. https://doi.org/10.1002/hsr2.71238.Wu PJ, Tsay FW, Wu DC, Yang JC, Chuah SK, Chen KY et al. Sequential changes of antibiotic resistances of Helicobacter pylori in Taiwan from 2019 to 2024. World J Gastroenterol. 2025;31(39):111380. https://doi.org/10.3748/wjg.v31.i39.111380.Wu PJ, Tsay FW, Wu DC, Yang JC, Chuah SK, Chen KY et al. Sequential changes of antibiotic resistances of Helicobacter pylori in Taiwan from 2019 to 2024. World J Gastroenterol. 2025;31(39):111380. https://doi.org/10.3748/wjg.v31.i39.111380.Podder V, Patel P, Sadiq NM. Levofloxacin. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2026. Available at: https://www.ncbi.nlm.nih.gov/books/NBK545180.Podder V, Patel P, Sadiq NM. Levofloxacin. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2026. Available at: https://www.ncbi.nlm.nih.gov/books/NBK545180.Hooper DC, Jacoby GA. Topoisomerase Inhibitors: Fluoroquinolone Mechanisms of Action and Resistance. Cold Spring Harb Perspect Med. 2016;6(9):a025320. https://doi.org/10.1101/cshperspect.a025320.Hooper DC, Jacoby GA. Topoisomerase Inhibitors: Fluoroquinolone Mechanisms of Action and Resistance. Cold Spring Harb Perspect Med. 2016;6(9):a025320. https://doi.org/10.1101/cshperspect.a025320.Le Tran TN, Bui NN, Nguyen VT, Tran NA. Novel DNA gyrase mutations in levofloxacin-resistant Helicobacter pylori isolates from southern Vietnam. J Microbiol Immunol Infect. 2025;58(4):455–462. https://doi.org/10.1016/j.jmii.2025.03.012.Le Tran TN, Bui NN, Nguyen VT, Tran NA. Novel DNA gyrase mutations in levofloxacin-resistant Helicobacter pylori isolates from southern Vietnam. J Microbiol Immunol Infect. 2025;58(4):455–462. https://doi.org/10.1016/j.jmii.2025.03.012.Šamanić I, Dadić B, Sanader Maršić Ž, Dželalija M, Maravić A, Kalinić H et al. Molecular Characterization and Mutational Analysis of Clarithromycinand Levofloxacin-Resistance Genes in Helicobacter pylori from Gastric Biopsies in Southern Croatia. Int J Mol Sci. 2023;24(19):14560. https://doi.org/10.3390/ijms241914560.Šamanić I, Dadić B, Sanader Maršić Ž, Dželalija M, Maravić A, Kalinić H et al. Molecular Characterization and Mutational Analysis of Clarithromycinand Levofloxacin-Resistance Genes in Helicobacter pylori from Gastric Biopsies in Southern Croatia. Int J Mol Sci. 2023;24(19):14560. https://doi.org/10.3390/ijms241914560.Yu Y, Xue J, Lin F, Liu D, Zhang W, Ru S, Jiang F. Global Primary Antibiotic Resistance Rate of Helicobacter pylori in Recent 10 years: A Systematic Review and Meta-Analysis. Helicobacter. 2024;29(3):e13103. https://doi.org/10.1111/hel.13103.Yu Y, Xue J, Lin F, Liu D, Zhang W, Ru S, Jiang F. Global Primary Antibiotic Resistance Rate of Helicobacter pylori in Recent 10 years: A Systematic Review and Meta-Analysis. Helicobacter. 2024;29(3):e13103. https://doi.org/10.1111/hel.13103.Kuo CJ, Lin CY, Le PH, Chang PY, Lai CH, Lin WR et al. Rescue therapy with rifabutin regimen for refractory Helicobacter pylori infection with dual drug-resistant strains. BMC Gastroenterol. 2020;20(1):218. https://doi.org/10.1186/s12876-020-01370-4.Kuo CJ, Lin CY, Le PH, Chang PY, Lai CH, Lin WR et al. Rescue therapy with rifabutin regimen for refractory Helicobacter pylori infection with dual drug-resistant strains. BMC Gastroenterol. 2020;20(1):218. https://doi.org/10.1186/s12876-020-01370-4.Borraccino AV, Celiberto F, Pricci M, Girardi B, Iannone A, Rendina M et al. Rifabutin as salvage therapy for Helicobacter pylori eradication: Cornerstones and novelties. World J Gastroenterol. 2022;28(45):6356–6362. https://doi.org/10.3748/wjg.v28.i45.6356.Borraccino AV, Celiberto F, Pricci M, Girardi B, Iannone A, Rendina M et al. Rifabutin as salvage therapy for Helicobacter pylori eradication: Cornerstones and novelties. World J Gastroenterol. 2022;28(45):6356–6362. https://doi.org/10.3748/wjg.v28.i45.6356.Heep M, Odenbreit S, Beck D, Decker J, Prohaska E, Rieger U, Lehn N. Mutations at four distinct regions of the rpoB gene can reduce the susceptibility of Helicobacter pylori to rifamycins. Antimicrob Agents Chemother. 2000;44(6):1713–1715. https://doi.org/10.1128/AAC.44.6.1713-1715.2000.Heep M, Odenbreit S, Beck D, Decker J, Prohaska E, Rieger U, Lehn N. Mutations at four distinct regions of the rpoB gene can reduce the susceptibility of Helicobacter pylori to rifamycins. Antimicrob Agents Chemother. 2000;44(6):1713–1715. https://doi.org/10.1128/AAC.44.6.1713-1715.2000.Nyssen OP, Espada M and Gisbert JP. Empirical vs. Susceptibility-Guided Treatment of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis. Front Microbiol. 2022;13:913436. https://doi.org/10.3389/fmicb.2022.913436.Nyssen OP, Espada M and Gisbert JP. Empirical vs. Susceptibility-Guided Treatment of Helicobacter pylori Infection: A Systematic Review and MetaAnalysis. Front Microbiol. 2022;13:913436. https://doi.org/10.3389/fmicb.2022.913436.Washburn M, Bejcek A, Grimbergen A, Youens K. S945 Diagnostic Yield of Gastric Biopsies for H. pylori. Am J Gastroenterol. 2024;119(10S):S659. https://doi.org/10.14309/01.ajg.0001033148.41536.e6.Washburn M, Bejcek A, Grimbergen A, Youens K. S945 Diagnostic Yield of Gastric Biopsies for H. pylori. Am J Gastroenterol. 2024;119(10S):S659. https://doi.org/10.14309/01.ajg.0001033148.41536.e6.Varier S, Mansingh M, Patel D, Desai B, Shah YM, Omar MA. Improving Helicobacter pylori Treatment Standards: A Quality Improvement Project Against Maastricht VI Guidelines. Cureus. 2025;17(12):e100058. https://doi.org/10.7759/cureus.100058.Varier S, Mansingh M, Patel D, Desai B, Shah YM, Omar MA. Improving Helicobacter pylori Treatment Standards: A Quality Improvement Project Against Maastricht VI Guidelines. Cureus. 2025;17(12):e100058. https://doi.org/10.7759/cureus.100058.Бакулина НВ, Савилова ИВ, Кондакова МН, Бордин ДС. Следует ли рекомендовать применение рифабутина и рифампицина для эрадикации Helicobacter pylori в России? Эффективная фармакотерапия. 2022;18(42):54–59. Режим доступа: https://umedp.ru/articles/sleduet_li_rekomendovat_primenenie_rifabutina_i_rifampitsina_dlya_eradikatsii_helicobacter_pylori_v_.html.Bakulina NV, Savilova IV, Kondakova MN, Bordin DS. Should We Recommend the Use of Rifabutin and Rifampicin for pylori Eradication in Russia? Effective Pharmacotherapy. 2022;18(42):54–59. (In Russ.) Available at: https://umedp.ru/articles/sleduet_li_rekomendovat_primenenie_rifabutina_i_rifampitsina_dlya_eradikatsii_helicobacter_pylori_v_.html.Ralhan K, Iyer KA, Diaz LL, Bird R, Maind A, Zhou QA. Navigating antibacterial frontiers: a panoramic exploration of antibacterial landscapes, resistance mechanisms, and emerging therapeutic strategies. ACS Infect Dis. 2024;10(5):1483–1519. https://doi.org/10.1021/acsinfecdis.4c00115.Ralhan K, Iyer KA, Diaz LL, Bird R, Maind A, Zhou QA. Navigating antibacterial frontiers: a panoramic exploration of antibacterial landscapes, resistance mechanisms, and emerging therapeutic strategies. ACS Infect Dis. 2024;10(5):1483–1519. https://doi.org/10.1021/acsinfecdis.4c00115.Nguyen HT, Van Duong T, Taylor LS. Enteric coating of tablets containing an amorphous solid dispersion of an enteric polymer and a weakly basic drug: A strategy to enhance in vitro release. Int J Pharm. 2023;642:123139. https://doi.org/10.1016/j.ijpharm.2023.123139.Nguyen HT, Van Duong T, Taylor LS. Enteric coating of tablets containing an amorphous solid dispersion of an enteric polymer and a weakly basic drug: A strategy to enhance in vitro release. Int J Pharm. 2023;642:123139. https://doi.org/10.1016/j.ijpharm.2023.123139.Serebrova S, Kurguzova D, Krasnykh L, Vasilenko G, Drozdov V, Lazareva N et al. Potential factors of Helicobacter pylori resistance to clarithromycin. Drug Metab Pers Ther. 2022;37(4):383–391. https://doi.org/10.1515/dmpt2021-0193.Serebrova S, Kurguzova D, Krasnykh L, Vasilenko G, Drozdov V, Lazareva N et al. Potential factors of Helicobacter pylori resistance to clarithromycin. Drug Metab Pers Ther. 2022;37(4):383–391. https://doi.org/10.1515/dmpt2021-0193.

The authors declare that there are no conflicts of interest present.