medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2021-17-1medsovet-6387Research ArticleШКОЛА ПЕДИАТРАPEDIATRICIAN SCHOOLПодходы к профилактике антибиотик-ассоциированной диареи у детейApproaches to prevention of antibiotic-associated diarrhea in childrenhttps://orcid.org/0000-0002-2258-8859ПахомовскаяН. Л.PakhomovskaiaN. L.

Пахомовская Надежда Леонидовна - кандидат медицинских наук, врач-гастроэнтеролог консультативного отделения консультативно-диагностического центра.

119296, Москва, Ломоносовский проспект, д. 2, стр. 1

Nadezhda L. Pakhomovskaia, Cand. Sci. (Med.), GastroenteroLogist of the Advisory Department of the ConsuLtative and Diagnostic Centre.

2, BLdg. 1, Lomonosovskiy Ave., Moscow, 119926

chexonte76@mail.ruТатьянинаО. Ф.TatyaninaO. F.

Татьянина Ольга Федоровна - кандидат медицинских наук, врач-гастроэнтеролог консультативного отделения консультативно-диагностического центра.

119296, Москва, Ломоносовский проспект, д. 2, стр. 1

Olga F. Tatyanina, Cand. Sci. (Med.), GastroenteroLogist of the Advisory Department of the ConsuLtative and Diagnostic Centre.

2, BLdg. 1, Lomonosovskiy Ave., Moscow, 119926

olgatatyanina@gmail.comЛазареваТ. Ю.LazarevaТ. Yu.

Лазарева Татьяна Юрьевна - врач-педиатр консультативного отделения консультативно-диагностического центра.

119296, Москва, Ломоносовский проспект, д. 2, стр. 1

Tatyana Yu. Lazareva, Pediatrician of the Advisory Department of the ConsuLtative and Diagnostic Centre.

2, BLdg. 1, Lomonosovskiy Ave., Moscow, 119926

lazareva_tanya87@mail.ruНациональный медицинский исследовательский центр здоровья детейРоссияNational Medical Research Center for Children’s HealthRussian Federation202131102021017283292Copyright © Пахомовская Н.Л., Татьянина О.Ф., Лазарева Т.Ю., 20212021Пахомовская Н.Л., Татьянина О.Ф., Лазарева Т.Ю.Pakhomovskaia N.L., Tatyanina O.F., Lazareva Т.Y.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/6387

Частота развития антибиотик-ассоциированной диареи, по данным различных авторов, колеблется от 5 до 39% случаев и зависит от возраста пациента и других сопутствующих факторов. Причиной возникновения антибиотик-ассоциированной диареи может быть любой антибиотик независимо от лекарственной формы и способа введения препарата. В детской популяции распространенность антибиотик-ассоциированной диареи варьирует от 6 до 70%. Актуальной проблемой является развитие данного заболевания на фоне проведения курса эрадикационной терапии H. pylori, что значительно затрудняет переносимость и приверженность терапии.

В статье представлены современные данные о патогенезе и факторах риска антибитик-ассоциированной диареи у детей. Клиническая картина заболевания варьирует от идиопатического энтерита до антибиотик-ассоциированной диареи, обусловленной Сl. difficile – псевдомембранозного колита.

Главный принцип лечения антибиотик-ассоциированной диареи – отмена антибактериального препарата, который вызвал развитие диареи, или снижение его дозы (если позволяет течение заболевания). В комплексном лечении используют сорбенты, проводят коррекцию водно-электролитного баланса. Применение пробиотиков представляется вполне логичным для лечения и профилактики антибиотик-ассоциированной диареи с точки зрения патогенеза данного состояния. Для коррекции дисбиоза применяют препараты, направленные на поддержание и восстановление количественного и качественного состава кишечной микробиоты. С учетом современных рекомендаций представлены основные группы препаратов (пробиотики, пребиотики, синбиотики), используемых для коррекции микробиоценоза кишечника. Рассмотрен механизм действия пробиотиков и механизмы их влияния на кишечную микрофлору. Представлены основные требования к штаммам бактерий, которые входят в состав пробиотических препаратов.

С учетом позиций доказательной медицины приводятся результаты рандомизированных клинических исследований и метаанализов, подтверждающих необходимость включения пробиотических комплексов в  схемы лечения антибиотик-ассоциированной диареи. Рассматриваются клинические эффекты штаммов Lactobacillus spp., Bifidobacterium spp., Streptococcus spp. и Lactococcus spp. на микробиоту пищеварительного тракта.

Отдельно обсуждается роль синбиотика, содержащего в одной капсуле 9 пробиотических штаммов в количестве 4,5 × 109 КОЕ и пребиотический компонент фруктоолигосахариды, в профилактике лечения антибиотик-ассоциированной диареи у детей. Результаты микробиологических исследований подтвердили наличие микроорганизмов родов Bifidobacterium, Lactobacillus, Streptococcus в продукте, причем содержание бактерий в одной дозе комплекса составило не менее 2 х 1010 KOЕ.

The incidence of antibiotic-associated diarrhea, according to various authors, ranges from 5 to 39% and depends on the patient’s age and other contributing factors. Antibiotic-associated diarrhea can be caused by any antibiotic, regardless of dosage form or route of administration. In the pediatric population, the prevalence of antibiotic-associated diarrhea ranges from 6 to 70%. An urgent problem is the development of this disease against the background of a course of H. pylori eradication therapy, which significantly complicates tolerance and adherence to therapy. This article presents current data on the pathogenesis and risk factors of antibiotic-associated diarrhea in children. The clinical picture ranges from idiopathic enteritis to antibiotic-associated diarrhea caused by Cl. difficile - pseudomembranous colitis.

The main principle of antibiotic-associated diarrhea treatment is cancellation of the antibacterial medicine that caused the diarrhea, or reducing its dose (if the course of the disease allows it). In complex treatment sorbents are used, correction of water-electrolyte balance is carried out. The use of probiotics seems quite logical for the treatment and prevention of antibiotic-associated diarrhea in terms of the pathogenesis of this condition. To correct dysbiosis, drugs are used to maintain and restore the quantitative and qualitative composition of the intestinal microbiota.

Taking into account modern recommendations the main groups of drugs (probiotics, prebiotics, synbiotics) used for correction of intestinal microbiocenosis are presented. The mechanism of action of probiotics and mechanisms of their effect on intestinal microflora are considered. The basic requirements for bacterial strains that are part of the probiotic drugs are presented.

The results of various randomized clinical trials and meta-analyses confirming the necessity of including probiotic complexes in antibiotic-associated diarrhea treatment regimens are presented from an evidence-based medicine perspective. The clinical effects of strains of Lactobacillusspp., Bifidobacterium spp.,Streptococcusspp. and Lactococcusspp. on the digestive tract microbiota are considered. The role of a synbiotic containing 9 probiotic strains of 4.5 * 109 CFU in one capsule and the prebiotic component fructooligosac-charides in the prevention of antibiotic-associated diarrhea in children is discussed separately. The results of microbiological studies confirmed the presence of microorganisms of genera Bifidobacterium, Lactobacillus, Streptococcus in the product, and the content of bacteria in one dose of the product was not less than 2 x 1010 CFU.

микробиотадетиатибиотик-ассоциированная диареяпсевдомембранозный колитпробиотикисинбиотикиmicrobiotachildrenantibiotic-associated diarrheapseudomembranous colitisprobioticssynbioticsСтатья подготовлена при поддержке АО «АЛИУМ», которому была предоставлена возможность ознакомиться с предварительной версией этой публикации на предмет фактической точностиThe article was prepared with the support of ALIUM JSC, which was given the opportunity to review a preliminary version of this publication for factual accuracyReferencesКаннер Е.В., Горелов А.В., Максимов М.Л., Ермолаева А.С., Булгакова И.С. Какие способы профилактики и лечения антибиотик-ассоциированной диареи у детей существуют в настоящее время? Медицинский совет. 2020;(1):177–184. https://doi.org/10.21518/2079-701X-2020-1-177-184.Kanner E.V., Gorelov A.V., Maksimov M.L., Ermolayeva A.S., Bulgakova I.S. Whan methods are currently available to prevent and treat antibiotic-associated diarrhea in children? Meditsinskiy sovet = Medical Council. 2020;(1):177–184. (In Russ.) https://doi.org/10.21518/2079-701X-2020-1-177-184.Makins R., Ballinger A. Gastrointestinal side effects of drugs. Expert Opin Drug Saf. 2003;2(4):421–429 https://doi.org/10.1517/14740338.2.4.421.Makins R., Ballinger A. Gastrointestinal side effects of drugs. Expert Opin Drug Saf. 2003;2(4):421–429 https://doi.org/10.1517/14740338.2.4.421.Beaugerie L., Petit J.-C. Antibiotic-associated diarrhea. Best Pract Res Clin Gastroenterol. 2004;18(2):337–352. https://doi.org/10.1016/j.bpg.2003.10.002.Beaugerie L., Petit J.-C. Antibiotic-associated diarrhea. Best Pract Res Clin Gastroenterol. 2004;18(2):337–352. https://doi.org/10.1016/j.bpg.2003.10.002.Giannelli F.R. Antibiotic-associated diarrhea. JAAPA. 2017;30(10):46–47. https://doi.org/10.1097/01.jaa.0000524721.01579.c9.Giannelli F.R. Antibiotic-associated diarrhea. JAAPA. 2017;30(10):46–47. https://doi.org/10.1097/01.jaa.0000524721.01579.c9.Hickson M. Probiotics in the prevention of antibiotic-associated diarrhoea and Clostridium difficile infection. Therap Adv Gastroenterol. 2011;4(3):185–197. https://doi.org/10.1177/1756283x11399115.Hickson M. Probiotics in the prevention of antibiotic-associated diarrhoea and Clostridium difficile infection. Therap Adv Gastroenterol. 2011;4(3):185–197. https://doi.org/10.1177/1756283x11399115.Захаренко С.М., Андреева И.В., Стецюк О.У. Нежелательные лекарственные реакции со стороны ЖКТ и антибиотикоассоциированная диарея при применении антибиотиков в амбулаторной практике: профилактика и лечение. Клиническая микробиология и антимикробная химиотера­ пия. 2019;21(3):196–206. https://doi.org/10.36488/cmac.2019.3.196-206.Zakharenko S.M., Andreeva I.V., Stetsiouk O.U. Gastrointestinal adverse drug reactions and antibiotic-associated diarrhea during antibiotic therapy in outpatient practice: prevention and treatment. Klinicheskaia mikrobiologiia i antimik­ robnaia khimioterapiia = Clinical Microbiology and Antimicrobial Chemotherapy. 2019;21(3):196–206. (In Russ.) https://doi.org/10.36488/cmac.2019.3.196-206.Sanches B., Coelho L., Moretzsohn L., Vieira G.Jr. Failure of Helicobacter pylori treatment after regimes containing clarithromycin: new practical therapeutic options. Helicobacter. 2008;13(6):572–576. https://doi.org/10.1111/j.1523-5378.2008.00649.x.Sanches B., Coelho L., Moretzsohn L., Vieira G.Jr. Failure of Helicobacter pylori treatment after regimes containing clarithromycin: new practical therapeutic options. Helicobacter. 2008;13(6):572–576. https://doi.org/10.1111/j.1523-5378.2008.00649.x.Jernberg C., Lofmark S., Edlund C., Jansson J.K. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 2007;1(1):56–66. https://doi.org/10.1038/ismej.2007.3.Jernberg C., Lofmark S., Edlund C., Jansson J.K. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 2007;1(1):56–66. https://doi.org/10.1038/ismej.2007.3.Löfmark S., Jernberg C., Jansson J.K., Edlund C. Clindamycininduced enrichment and longterm persistence of resistant Bacteroides spp. and resistance genes. J Antimicrob Chemother. 2006;58(6):1160–1167. https://doi.org/10.1093/jac/dkl420.Löfmark S., Jernberg C., Jansson J.K., Edlund C. Clindamycininduced enrichment and longterm persistence of resistant Bacteroides spp. and resistance genes. J Antimicrob Chemother. 2006;58(6):1160–1167. https://doi.org/10.1093/jac/dkl420.Dethlefsen L., Huse S., Sogin M.L., Relman D.A. The Pervasive Effects of an Antibiotic on the Human Gut Microbiota, as Revealed by Deep 16S rRNA Sequencing. PLoS Biol. 2008;6(11):2383–2400. https://doi.org/10.1371/journal.pbio.0060280.Dethlefsen L., Huse S., Sogin M.L., Relman D.A. The Pervasive Effects of an Antibiotic on the Human Gut Microbiota, as Revealed by Deep 16S rRNA Sequencing. PLoS Biol. 2008;6(11):2383–2400. https://doi.org/10.1371/journal.pbio.0060280.Turck D., Bernet J.P., Marx J., Kempf H., Giard P., Walbaum O. et al. Incidence and risk factors of oral antibiotic-associated diarrhea in an outpatient pediatric population. J Pediatr Gastroenterol Nutr. 2003;37(1):22–26. https://doi.org/10.1097/00005176-200307000-00004.Turck D., Bernet J.P., Marx J., Kempf H., Giard P., Walbaum O. et al. Incidence and risk factors of oral antibiotic-associated diarrhea in an outpatient pediatric population. J Pediatr Gastroenterol Nutr. 2003;37(1):22–26. https://doi.org/10.1097/00005176-200307000-00004.Högenauer C., Hammer H.F., Krejs G.J., Reisinger E.C. Mechanisms and management of antibiotic-associated diarrhea. Clin Infect Dis. 1998;27(4):702–710. https://doi.org/10.1086/514958.Högenauer C., Hammer H.F., Krejs G.J., Reisinger E.C. Mechanisms and management of antibiotic-associated diarrhea. Clin Infect Dis. 1998;27(4): 702–710. https://doi.org/10.1086/514958.Kyne L., Warny M., Qamar A., Kelly C.P. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med. 2000;342(6):390–397. https://doi.org/10.1056/nejm200002103420604.Kyne L., Warny M., Qamar A., Kelly C.P. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med. 2000;342(6):390–397. https://doi.org/10.1056/nejm200002103420604.O’Connor J.R., Johnson S., Gerding D.N. Clostridium difficile infection caused by the epidemic BI/NAP1/027 strain. Gastroenterology. 2009;136(6):1913–1924. http://doi.org/10.1053/j.gastro.2009.02.073.O’Connor J.R., Johnson S., Gerding D.N. Clostridium difficile infection caused by the epidemic BI/NAP1/027 strain. Gastroenterology. 2009;136(6):1913–1924. http://doi.org/10.1053/j.gastro.2009.02.073.Surawicz C.M., Brandt L.J., Binion D.G., Ananthakrishnan A.N., Scott C.R., Peter G.H. et al. Guidelines for diagnosis, treatment and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108(4):478–498. https://doi.org/10.1038/ajg.2013.4.Surawicz C.M., Brandt L.J., Binion D.G., Ananthakrishnan A.N., Scott C.R., Peter G.H. et al. Guidelines for diagnosis, treatment and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108(4):478–498. https://doi.org/10.1038/ajg.2013.4.Ивашкин В.Т., Ющук Н.Д., Маев И.В., Лапина Т.Л., Полуэктова Е.А., Шифрин О.С. и др. Рекомендации Российской гастроэнтерологической ассоциации по диаг ностике и лечению Clostridium difficile-ассоциированной болезни. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2016;5(26):56–65. https://doi.org/10.22416/1382-4376-2016-26-5-56-65.Ivashkin V.T., Yushchuk N.D., Mayev I.V., Lapina Т.L., Poluektova Ye.A., Shifrin O.S. et al. Diagnostics and treatment of Clostridium difficile-associated disease: Guidelines of the Russian gastroenterological association. Rossiyskiy zhurnal gastroenterologii, gepatologii, koloproctologii = Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2016;5(26):56–65. (In Russ.) https://doi.org/10.22416/1382-4376-2016-26-5-56-65.Walk S.T., Micic D., Jain R., Lo E.S., Trivedi I., Liu E.W. et al. Clostridium difficile ribotype does not predict severe infection. Clin Infect Dis. 2012;55(12):1661–1668. https://doi.org/10.1093/cid/cis786.Walk S.T., Micic D., Jain R., Lo E.S., Trivedi I., Liu E.W. et al. Clostridium difficile ribotype does not predict severe infection. Clin Infect Dis. 2012;55(12):1661–1668. https://doi.org/10.1093/cid/cis786.Wiström J., Norrby S.R., Myhre E.B., Eriksson S., Granström G., Lagergren L. et al. Frequency of antibiotic-associated diarrhea in 2462 antibiotic-treated hospitalized patients: a prospective study. J Antimicrob Chemother. 2001;47(1):43–50. https://doi.org/10.1093/jac/47.1.43.Wiström J., Norrby S.R., Myhre E.B., Eriksson S., Granström G., Lagergren L. et al. Frequency of antibiotic-associated diarrhea in 2462 antibiotic-treated hospitalized patients: a prospective study. J Antimicrob Chemother. 2001;47(1):43–50. https://doi.org/10.1093/jac/47.1.43.Surawicz C.M., Brandt L.J., Binion D.G., Ananthakrishnan A.N., Curry S.R., Gilligan P.H. et al. Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections. American Journal of Gastroenterology. 2013;108(4):478–498. https://doi.org/10.1038/ajg.2013.4.Surawicz C.M., Brandt L.J., Binion D.G., Ananthakrishnan A.N., Curry S.R., Gilligan P.H. et al. Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections. American Journal of Gastroenterology. 2013;108(4):478–498. https://doi.org/10.1038/ajg.2013.4.Hill C., Guarner F., Reid G., Gibson G.R., Merenstein D.J., Pot B. et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotics. Nat Rev Gasroenterol Hepatol. 2014;11(8):506–514. https://doi.org/10.1038/nrgastro.2014.66.Hill C., Guarner F., Reid G., Gibson G.R., Merenstein D.J., Pot B. et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotics. Nat Rev Gasroenterol Hepatol. 2014;11(8):506–514. https://doi.org/10.1038/nrgastro.2014.66.Szajewska H., Canani R.B., Guarino A., Hojsak I., Indrio F., Kolacek S. et al. Probiotics for the Prevention of Antibiotic-Associated Diarrhea in Children. J Pediatr Gastroenterol Nutr. 2016;62(3):495–506. https://doi.org/10.1097/mpg.0000000000001081.Szajewska H., Canani R.B., Guarino A., Hojsak I., Indrio F., Kolacek S. et al. Probiotics for the Prevention of Antibiotic-Associated Diarrhea in Children. J Pediatr Gastroenterol Nutr. 2016;62(3):495–506. https://doi.org/10.1097/mpg.0000000000001081.Guarner F., Sanders M.E., Eliakim R., Fedorak R., Gangl A., Garish J. et al. Probiotics and prebiotics. February 2017. Available at: https://www.world-gastroenterology.org/guidelines/global-guidelines/probiotics-and-prebiotics/probiotics-and-prebiotics-english.Guarner F., Sanders M.E., Eliakim R., Fedorak R., Gangl A., Garish J. et al. Probiotics and prebiotics. February 2017. Available at: https://www.world-gastroenterology.org/guidelines/global-guidelines/probiotics-and-prebiotics/probiotics-and-prebiotics-english.Shen N.T., Maw A., Tmanova L.L., Pino A., Ancy K., Crawford C.V. et al. Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression Analysis. Gastroenterology. 2017;152(8):1889–1900. https://doi.org/10.1053/j.gastro.2017.02.003.Shen N.T., Maw A., Tmanova L.L., Pino A., Ancy K., Crawford C.V. et al. Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression Analysis. Gastroenterology. 2017;152(8):1889–1900. https://doi.org/10.1053/j.gastro.2017.02.003.Liao W., Chen C., Wen T., Zhao Q. Probiotics for the Prevention of Antibiotic-associated Diarrhea in Adults. A Meta-Analysis of Randomized Placebo-Controlled Trials. J Clin Gastroenterol. 2021;55(6):469–480. https://doi.org/10.1097/mcg.0000000000001464.Liao W., Chen C., Wen T., Zhao Q. Probiotics for the Prevention of Antibiotic-associated Diarrhea in Adults. A Meta-Analysis of Randomized Placebo-Controlled Trials. J Clin Gastroenterol. 2021;55(6):469–480. https://doi.org/10.1097/mcg.0000000000001464.Armuzzi A., Cremonini F., Ojetti V., Bartolozzi F., Canducci F., Candelli M. et al. Effect of Lactobacillus GG supplementation on antibiotic-associated gastrointestinal side effects during Helicobacter pylori eradication therapy: a pilot study. Digestion. 2001;63(1):1–7. https://doi.org/10.1159/000051865.Armuzzi A., Cremonini F., Ojetti V., Bartolozzi F., Canducci F., Candelli M. et al. Effect of Lactobacillus GG supplementation on antibiotic-associated gastrointestinal side effects during Helicobacter pylori eradication therapy: a pilot study. Digestion. 2001;63(1):1–7. https://doi.org/10.1159/000051865.Zhang M.M., Qian W., Qin Y.Y., He J., Zhou Y.H. Probiotics in Helicobacter pylori eradication therapy: a systematic review and meta-analysis. World J Gastro­ enterol. 2015;21(14):4345–4347. https://doi.org/10.3748%2Fwjg.v21.i14.4345.Zhang M.M., Qian W., Qin Y.Y., He J., Zhou Y.H. Probiotics in Helicobacter pylori eradication therapy: a systematic review and meta-analysis. World J Gastro­ enterol. 2015;21(14):4345–4347. https://doi.org/10.3748%2Fwjg.v21.i14.4345.Lü M., Yu S., Deng J., Yan Q., Yang C., Xia G. et al. Efficacy of Probiotic Supplementation Therapy for Helicobacter pylori Eradication: A Meta-Analysis of Randomized Controlled Trials. PLoS ONE. 2016;11(10):e0163743. https://doi.org/10.1371/journal.pone.0163743.Lü M., Yu S., Deng J., Yan Q., Yang C., Xia G. et al. Efficacy of Probiotic Supplementation Therapy for Helicobacter pylori Eradication: A Meta-Analysis of Randomized Controlled Trials. PLoS ONE. 2016;11(10):e0163743. https://doi.org/10.1371/journal.pone.0163743.Si X.B., Lan Y., Qiao L. A meta-analysis of randomized controlled trials of bismuth-containing quadruple therapy combined with probiotic supplement for eradication of Helicobacter pylori. Zhonghua Nei Ke Za Zhi. 2017;56(10):752– 759. https://doi.org/10.3760/cma.j.issn.0578-1426.2017.10.009.Si X.B., Lan Y., Qiao L. A meta-analysis of randomized controlled trials of bismuth-containing quadruple therapy combined with probiotic supplement for eradication of Helicobacter pylori. Zhonghua Nei Ke Za Zhi. 2017;56(10):752–759. https://doi.org/10.3760/cma.j.issn.0578-1426.2017.10.009.Fang H.R., Zhang G.Q., Cheng J.Y., Li Z.Y. Efficacy of Lactobacillus-supplemented triple therapy for Helicobacter pylori infection in children: a meta-analysis of randomized controlled trials. Eur J Pediatr. 2019;178(1):7–16. https://doi.org/10.1007/s00431-018-3282-z.Fang H.R., Zhang G.Q., Cheng J.Y., Li Z.Y. Efficacy of Lactobacillus-supplemented triple therapy for Helicobacter pylori infection in children: a meta-analysis of randomized controlled trials. Eur J Pediatr. 2019;178(1):7–16. https://doi.org/10.1007/s00431-018-3282-z.Lv Z., Wang B., Zhou X., Wang F., Xie Y., Zheng H., Lv N. Efficacy and safety of probiotics as adjuvant agents for Helicobacter pylori infection: A metaanalysis. Exp Ther Med. 2015;9(3):707–716. https://doi.org/10.3892/etm.2015.2174.Lv Z., Wang B., Zhou X., Wang F., Xie Y., Zheng H., Lv N. Efficacy and safety of probiotics as adjuvant agents for Helicobacter pylori infection: A metaanalysis. Exp Ther Med. 2015;9(3):707–716. https://doi.org/10.3892/etm.2015.2174.Shi X., Zhang J., Mo L., Shi J., Qin M., Huang X. Efficacy and safety of probiotics in eradicating Helicobacter pylori: A network meta-analysis. Medicine (Baltimore). 2019;98(15):e15180. https://doi.org/10.1097/md.0000000000015180.Shi X., Zhang J., Mo L., Shi J., Qin M., Huang X. Efficacy and safety of probiotics in eradicating Helicobacter pylori: A network meta-analysis. Medicine (Baltimore). 2019;98(15):e15180. https://doi.org/10.1097/md.0000000000015180.Guo Q., Goldenberg J.Z., Humphrey C., Dib R.E., Johnston B.C. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev. 2019;4(4):CD004827. Available at: https://pubmed.ncbi.nlm.nih.gov/31039287/.Guo Q., Goldenberg J.Z., Humphrey C., Dib R.E., Johnston B.C. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev. 2019;4(4):CD004827. Available at: https://pubmed.ncbi.nlm.nih.gov/31039287/.Valdés-Varela L., Hernández-Barranco A.M., Ruas-Madiedo P., Gueimonde M. Effect of Bifidobacterium upon Clostridium difficile Growth and Toxicity When Co-cultured in Different Prebiotic Substrates. Front Microbiol. 2016;7:738. https://doi.org/10.3389/fmicb.2016.00738.Valdés-Varela L., Hernández-Barranco A.M., Ruas-Madiedo P., Gueimonde M. Effect of Bifidobacterium upon Clostridium difficile Growth and Toxicity When Co-cultured in Different Prebiotic Substrates. Front Microbiol. 2016;7:738. https://doi.org/10.3389/fmicb.2016.00738.Goldenberg J.Z., Yap C., Lytvyn L., Lo C., Beardsley J., Mertz D., Johnston B.C. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017;12(12):CD006095. Available at: https://pubmed.ncbi.nlm.nih.gov/29257353/.Goldenberg J.Z., Yap C., Lytvyn L., Lo C., Beardsley J., Mertz D., Johnston B.C. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017;12(12): CD006095. Available at: https://pubmed.ncbi.nlm.nih.gov/29257353/.Шелыгин Ю.А., Алёшкин В.А., Сухина М.А., Миронов А.Ю., Брико Н.И., Козлов Р.С. и др. Клинические рекомендации национальной ассоциации специалистов по контролю инфекций, связанных с оказанием медицинской помощи, и общероссийской общественной некоммерческой организации «Ассоциация колопроктологов России» по диагностике и профилактике Clostridium difficile-ассоциированной диареи (CDI). Коло­ проктология. 2018;(3):7–23. Режим доступа: https://www.ruproctology.com/jour/article/view/1135/1135.Shelygin Yu.A., Aleshkin V.A., Sukhina M.A., Mironov A.Yu., Briko N.I., Kozlov R.S. et al. Сlinical recommendations of the national association of specialists for the healthcarerelated infections control and the russian association of coloproctology on diagnosis, treatment and prophylaxis of clostridium difficile-associated diarrhea (CDI). Koloproctologia. 2018;(3):7–23. (In Russ.) Available at: https://www.ruproctology.com/jour/article/view/1135/1135.Ивашкин В.Т., Маев И.В., Абдулганиева Д.И., Алексеенко С.А., Ивашкина Н.Ю., Корочанская Н.В. и др. Практические рекомендации Научного сообщества по содействию клиническому изучению микробиома человека (НСОИМ) и Российской гастроэнтерологической ассоциации (РГА) по применению пробиотиков для лечения и профилактики заболеваний гастроэнтерологического профиля у взрослых. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2020;30(2):76–89. https://doi.org/10.22416/1382-4376-2020-30-2-76-89.Ivashkin V.T., Mayev I.V., Abdulganieva D.I., Alekseenko S.A., Ivashkina N.Yu., Korochanskaya N.V. et al Practical Recommendations of Scientific Society for the Study of Human Microbiome and Russian Gastroenterological Association (RGA) for Probiotics in Treatment and Prevention of Gastroenterological Diseases in Adults. Rossiyskiy zhurnal gastroenterologii, gepatologii, kolo­ proctologii = Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020; 30(2):76-89. (In Russ.) https://doi.org/10.22416/1382-4376-2020-30-2-76-89.Shimizu К., Ogura H., Kabata D., Ojima M., Ikeda M., Shimazu T. et al. Association of prophylactic synbiotics with reduction in diarrhea and pneumonia in mechanically ventilated critically ill patients: A propensity score analysis. J Infect Chemother. 2018;24(10):795–801. https://doi.org/10.1016/j.jiac.2018.06.006.Shimizu К., Ogura H., Kabata D., Ojima M., Ikeda M., Shimazu T. et al. Association of prophylactic synbiotics with reduction in diarrhea and pneumonia in mechanically ventilated critically ill patients: A propensity score analysis. J Infect Chemother. 2018;24(10):795–801. https://doi.org/10.1016/j.jiac.2018.06.006.Плотникова Е.Ю., Гриневич В.Б., Захарова Ю.В., Грачева Т.Ю. Такие разные и одинаковые пробиотики – проблема выбора. Фарматека. 2019;26(2):97–105. Режим доступа: https://pharmateca.ru/archive/article/37177.Plotnikova E.Yu., Grinevich V.B., Zakharova Yu.V., Gracheva T.Yu. So different and the same probiotics – the problem of choice. Farmateka. 2019;26(2):97–105. (In Russ.) Available at: https://pharmateca.ru/archive/article/37177.Yue Y., He Z., Zhou Y., Ross R.P., Stanton C., Zhao J. et al. Lactobacillus plantarum relieves diarrhea caused by enterotoxin-producing Escherichia coli through inflammation modulation and gut microbiota regulation. Food Funct. 2020;11(12):10362–10374. https://doi.org/10.1039/d0fo02670k.Yue Y., He Z., Zhou Y., Ross R.P., Stanton C., Zhao J. et al. Lactobacillus plantarum relieves diarrhea caused by enterotoxin-producing Escherichia coli through inflammation modulation and gut microbiota regulation. Food Funct. 2020;11(12):10362–10374. https://doi.org/10.1039/d0fo02670k.Mahmud A.S.M., Chowdhury M., Akter R., Islam S., Mazumdar S., Taznin T. et al. In-vivo evaluation of the anti-diarrheal effect of Lactococcus lactis subspecies lactis and Lactococcus piscium isolated from yogurt. bioRxiv. 2020. https://doi.org/10.1101/2020.07.30.226688.Mahmud A.S.M., Chowdhury M., Akter R., Islam S., Mazumdar S., Taznin T. et al. In-vivo evaluation of the anti-diarrheal effect of Lactococcus lactis subspecies lactis and Lactococcus piscium isolated from yogurt. bioRxiv. 2020. https://doi.org/10.1101/2020.07.30.226688.Aloisio I., Santini C., Biavati B., Dinelli G., Cencič A., Chingwaru W. et al. Characterization of Bifidobacterium spp. strains for the treatment of enteric disorders in newborns. Appl Microbiol Biotechnol. 2012;96(6):1561–1576. https://doi.org/10.1007/s00253-012-4138-5.Aloisio I., Santini C., Biavati B., Dinelli G., Cencič A., Chingwaru W. et al. Characterization of Bifidobacterium spp. strains for the treatment of enteric disorders in newborns. Appl Microbiol Biotechnol. 2012;96(6):1561–1576. https://doi.org/10.1007/s00253-012-4138-5.Ojima M.N., Gotoh A., Takada H., Odamaki T., Xiao J.Z., Katoh T., Katayama T. Bifidobacterium bifidum Suppresses Gut Inflammation Caused by Repeated Antibiotic Disturbance Without Recovering Gut Microbiome Diversity in Mice. Front Microbiol. 2020;11:1349. https://doi.org/10.3389/fmicb.2020.01349.Ojima M.N., Gotoh A., Takada H., Odamaki T., Xiao J.Z., Katoh T., Katayama T. Bifidobacterium bifidum Suppresses Gut Inflammation Caused by Repeated Antibiotic Disturbance Without Recovering Gut Microbiome Diversity in Mice. Front Microbiol. 2020;11:1349. https://doi.org/10.3389/fmicb.2020.01349.Corrêa N.B.O., Péret Filho L.A., Penna F.J., Lima F. M. L., Nicoli J.R. A randomized formula controlled trial of Bifidobacterium lactis and Streptococcus thermophilus for prevention of antibiotic-associated diarrhea in infants. J Clin Gastroenterol. 2005;39(5):385–389. https://doi.org/10.1097/01.mcg.0000159217.47419.5b.Corrêa N.B.O., Péret Filho L.A., Penna F.J., Lima F. M. L., Nicoli J.R. A randomized formula controlled trial of Bifidobacterium lactis and Streptococcus thermophilus for prevention of antibiotic-associated diarrhea in infants. J Clin Gastroenterol. 2005;39(5):385–389. https://doi.org/10.1097/01.mcg.0000159217.47419.5b.Kolling G.L., Wu M., Warren C.A., Durmaz E., Klaenhammer T.R., Timko M.P., Guerrant R.L. Lactic acid production by Streptococcus thermophilus alters Clostridium difficile infection and in vitro Toxin A production. Gut Microbes. 2012;3(6):523–529. https://doi.org/10.4161/gmic.21757.Kolling G.L., Wu M., Warren C.A., Durmaz E., Klaenhammer T.R., Timko M.P., Guerrant R.L. Lactic acid production by Streptococcus thermophilus alters Clostridium difficile infection and in vitro Toxin A production. Gut Microbes. 2012;3(6):523–529. https://doi.org/10.4161/gmic.21757.Millette M., Nguyen A., Amine K.M., Lacroix M. Gastrointestinal survival of bacteria in commercial probiotic products. Intern J Prob Preb. 2013;8(4):149–156. Available at: https://www.researchgate.net/publication/285929818_Gastrointestinal_survival_of_bacteria_in_commercial_probiotic_products.Millette M., Nguyen A., Amine K.M., Lacroix M. Gastrointestinal survival of bacteria in commercial probiotic products. Intern J Prob Preb. 2013;8(4):149–156. Available at: https://www.researchgate.net/publication/285929818_ Gastrointestinal_survival_of_bacteria_in_commercial_probiotic_products.Карева Е.Н. НПВП-энтеропатия – перспективы профилактики и лечения. РМЖ. 2019;(7):11–14. Режим доступа: https://www.rmj.ru/articles/gastro-enterologiya/NPVP-enteropatiya__perspektivy_profilaktiki_i_lecheniya/.Kareva E.N. NSAID enteropathy - prospects for prevention and treatment. RMZH = RMJ. 2019;7:11–14. (In Russ.) Available at: https://www.rmj.ru/articles/gastroenterologiya/NPVP-enteropatiya__perspektivy_profilaktiki_i_lecheniya/.Guidelines on the assessment of bacterial susceptibility to antimicrobials of human or veterinary importance. EFSA J. 2012;10(6):2740–2750. Available at: https://www.efsa.europa.eu/it/efsajournal/pub/2740.Guidelines on the assessment of bacterial susceptibility to antimicrobials of human or veterinary importance. EFSA J. 2012;10(6):2740–2750. Available at: https://www.efsa.europa.eu/it/efsajournal/pub/2740.Klare I., Konstabel C., Werner G., Huys G., Vankerckhoven V., Kahlmeter G. et al. Antimicrobial susceptibilities of Lactobacillus, Pediococcus and Lactococcus human isolates and cultures intended for probiotic or nutritional use. J Antimicrob Chemother. 2007;59(5):900–912. https://doi.org/10.1093/jac/dkm035.Klare I., Konstabel C., Werner G., Huys G., Vankerckhoven V., Kahlmeter G. et al. Antimicrobial susceptibilities of Lactobacillus, Pediococcus and Lactococcus human isolates and cultures intended for probiotic or nutritional use. J Antimicrob Chemother. 2007;59(5):900–912. https://doi.org/10.1093/jac/dkm035.

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