antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»antibiotics-590Research ArticleСтатьиОценка лекарственной устойчивости пробиотических лактобациллEstimation of Probiotic Lactobacilli Drug ResistanceБрусликН. Л.BruslikN. L.noemail@neicon.ruАхатоваД. Р.AkhatovaD. R.noemail@neicon.ruТойменцеваА. А.ToimentsevaA. A.noemail@neicon.ruАбдулхаковС. Р.AbdulkhakovS. R.noemail@neicon.ruИльинскаяО. H.IlyinskayaO. N.noemail@neicon.ruЯруллинаД. Р.YarullinaD. R.noemail@neicon.ruИнститут фундаментальной медицины и биологииРоссияInstitute of Fundamental Medicine and BiologyRussian Federation201513052020603-4613Copyright © Бруслик Н.Л., Ахатова Д.Р., Тойменцева А.А., Абдулхаков С.Р., Ильинская О.H., Яруллина Д.Р., 20202020Бруслик Н.Л., Ахатова Д.Р., Тойменцева А.А., Абдулхаков С.Р., Ильинская О.H., Яруллина Д.Р.Bruslik N.L., Akhatova D.R., Toimentseva A.A., Abdulkhakov S.R., Ilyinskaya O.N., Yarullina D.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.antibiotics-chemotherapy.ru/jour/article/view/590

Проведён анализ устойчивости пробиотических лактобацилл к антибиотикам и лекарственным препаратам, применяемым при заболеваниях желудочно-кишечного тракта. У 19 штаммов рода Lactobacillus (14 штаммов L.fermentum, 4 штаммов L.plantarum и 1 штамма L.rhamnosus), выделенных из коммерческих пробиотиков и кисломолочных продуктов, определены уровни устойчивости к 14 антибиотикам различной природы: β-лактамам, аминогликозидам, макролидам, клиндамицину, ванкомицину, рифампицину, ципрофлоксацину, тетрациклину и хлорамфениколу. Практически все исследованные лактобациллы чувствительны к препаратам первой линии противохеликобактерной терапии - амоксициллину и кларитромицину, что делает нецелесообразным параллельный приём пробиотиков, содержащих изученные лактобациллы, при гастрите и язве желудка, несмотря на известную антагонистическую активность лактобацилл в отношении Helicobacter pylori. В то же время лактобациллы устойчивы к действию месалазина, поэтому могут применяться для коррекции дисбиоза при воспалительных заболеваниях кишечника.

An actual problem of analysis of probiotic lactobacilli resistance to antibiotics and other drugs used in the treatment of gastro-intestinal disturbances has been for the first time solved. The levels of resistance of 19 strains of Lactobacillus (14 strains of L.fermentum, 4 strains of L.plantarum and 1 strain of L.rhamnosus) isolated from commercial probiotics and sour milk products to 14 antibiotics of various nature, i.e. в-lactams, aminoglycosides, macrolides, clindamycin, vancomycin, rifampicin, ciprofloxacin, tetracycline and chloramphenicol were determined. All the isolates were practically susceptible to the drugs of the first line antihelicobacterial therapy, i.e. amoxicillin and clarithromycin, that makes inexpedient the parallel use of the probiotics containing the above lactobacilli in the treatment of gastritis and gastric ulcer, despite the lactobacilli antagonism with respect to Helicobacterpylory. Lactobacilli are as well resistant to mesalazin and can be used for correction of dysbiosis in inflammatory affections of the intestine.

пробиотические лактобациллылекарственная устойчивостьзаболевания желудочно-кишечного трактаprobiotic lactobacillidrug resistancegastro-intestinal diseasesReferencesSazawal S., Hiremath G., Dhingra U., Malik P., Deb S., Black R.E. Efficacy of probiotics in prevention of acute diarrhea: a meta-analysis of masked, randomised, placebo-controlled trials. Lancet Infect Dis 2006; 6: 374-382.Sazawal S., Hiremath G., Dhingra U., Malik P., Deb S., Black R.E. Efficacy of probiotics in prevention of acute diarrhea: a meta-analysis of masked, randomised, placebo-controlled trials. Lancet Infect Dis 2006; 6: 374-382.Pillai A., Nelson R. Probiotics for treatment of Clostridium dificile-associated colitis in adults. Cochrane Database Syst Rev 2008; 23: 1: CD004611.Pillai A., Nelson R. Probiotics for treatment of Clostridium dificile-associated colitis in adults. Cochrane Database Syst Rev 2008; 23: 1: CD004611.Ghouri Y.A., Richards D.M., Rahimi E.F., Krill J.T., Jelinek K.A., DuPont A.W. Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease. Clin Exp Gastroenterol 2014; 7: 473-487.Ghouri Y.A., Richards D.M., Rahimi E.F., Krill J.T., Jelinek K.A., DuPont A.W. Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease. Clin Exp Gastroenterol 2014; 7: 473-487.Matsuoka K., Kanai T. The gut microbiota and inflammatory bowel disease. Semin Immunopathol 2015; 37: 1: 47-55.Matsuoka K., Kanai T. The gut microbiota and inflammatory bowel disease. Semin Immunopathol 2015; 37: 1: 47-55.Camilleri M. Probiotics and irritable bowel syndrome: rationale, putative mechanisms, and evidence of clinical efficacy. J. Clin. Gastroenterol. 2006; 40: 264-269.Camilleri M. Probiotics and irritable bowel syndrome: rationale, putative mechanisms, and evidence of clinical efficacy. J. Clin. Gastroenterol. 2006; 40: 264-269.Rafter J., Bennett M., Caderni G., Clune Y., Hughes R., Karlsson P.C., Klinder A., O'Riordan M., O'Sullivan G.C., Pool-Zobel B., Rechkemmer G., Roller M., Rowland I., Salvadori M., Thijs H., Van Loo J., Watzl B., Collins J.K. Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients. Am J Clin Nutr 2007; 85: 488-496.Rafter J., Bennett M., Caderni G., Clune Y., Hughes R., Karlsson P.C., Klinder A., O'Riordan M., O'Sullivan G.C., Pool-Zobel B., Rechkemmer G., Roller M., Rowland I., Salvadori M., Thijs H., Van Loo J., Watzl B., Collins J.K. Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients. Am J Clin Nutr 2007; 85: 488-496.de Bortoli N., Leonardi G., Ciancia E., Merlo A., Bellini M., Costa F., Mumolo M.G., Ricchiuti A., Cristiani F., Santi S., Rossi M., Marchi S. Helicobacter pylori eradication: a randomized prospective study of triple therapy versus triple therapy plus lactoferrin and probiotics. Am J Gastroenterol 2007; 102: 5: 951-956.de Bortoli N., Leonardi G., Ciancia E., Merlo A., Bellini M., Costa F., Mumolo M.G., Ricchiuti A., Cristiani F., Santi S., Rossi M., Marchi S. Helicobacter pylori eradication: a randomized prospective study of triple therapy versus triple therapy plus lactoferrin and probiotics. Am J Gastroenterol 2007; 102: 5: 951-956.Cannon J.P., Lee T.A., Bolanos J.T., Danziger L.H. Pathogenic relevance of Lactobacillus: a retrospective review of over 200 cases. Eur J Clin Microbiol Infect Dis 2005; 24: 1: 31-40.Cannon J.P., Lee T.A., Bolanos J.T., Danziger L.H. Pathogenic relevance of Lactobacillus: a retrospective review of over 200 cases. Eur J Clin Microbiol Infect Dis 2005; 24: 1: 31-40.Mathur S., Singh R. Antibiotic resistance in food lactic acid bacteria - a review. Int J Food Microbiol 2005; 105: 3: 281-295.Mathur S., Singh R. Antibiotic resistance in food lactic acid bacteria - a review. Int J Food Microbiol 2005; 105: 3: 281-295.Devirgiliis C., Zinno P., Perozzi G. Update on antibiotic resistance in food-borne Lactobacillus and Lactococcusspecies. Front Microbiol 2013; 8; 4: 301.Devirgiliis C., Zinno P., Perozzi G. Update on antibiotic resistance in food-borne Lactobacillus and Lactococcusspecies. Front Microbiol 2013; 8; 4: 301.Виноградова К.А., Булгакова В.Г., Полин A.H., Кожевин П.А. Устойчивость микроорганизмов к антибиотикам: резистома, её объём, разнообразие и развитие. Антибиотики и химиотер. 2013; 58: 5-6: 38-48. 12.Виноградова К.А., Булгакова В.Г., Полин A.H., Кожевин П.А. Устойчивость микроорганизмов к антибиотикам: резистома, её объём, разнообразие и развитие. Антибиотики и химиотер. 2013; 58: 5-6: 38-48. 12.van Reenen C.A., Dicks L.M. Horizontal gene transfer amongst probiotic lactic acid bacteria and other intestinal microbiota: what are the possibilities? A review. Arch Microbiol 2011; 193: 3: 157-168.van Reenen C.A., Dicks L.M. Horizontal gene transfer amongst probiotic lactic acid bacteria and other intestinal microbiota: what are the possibilities? A review. Arch Microbiol 2011; 193: 3: 157-168.Bernardeau M., Vernoux J.P., Henri-Dubernet S., Guéguen M. Safety assessment of dairy microorganisms: the Lactobacillus genus. Int J Food Microbiol 2008; 126: 3: 278-285.Bernardeau M., Vernoux J.P., Henri-Dubernet S., Guéguen M. Safety assessment of dairy microorganisms: the Lactobacillus genus. Int J Food Microbiol 2008; 126: 3: 278-285.EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), 2008. Technical guidance on the update of the criteria used in the assessment of bacterial resistance to antibiotics of human or veterinary importance. The EFSA Journal 2008; 732: 1-15. 15.EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), 2008. Technical guidance on the update of the criteria used in the assessment of bacterial resistance to antibiotics of human or veterinary importance. The EFSA Journal 2008; 732: 1-15. 15.Определение чувствительности микроорганизмов к антибактериальным препаратам (МУК 4.2.1890-04). Клин Микробиол Антимикроб Химиотер 2004; 6: 4: 306-359.Определение чувствительности микроорганизмов к антибактериальным препаратам (МУК 4.2.1890-04). Клин Микробиол Антимикроб Химиотер 2004; 6: 4: 306-359.Danielsen M., Wind A. Susceptibility of Lactobacillus spp. to antimicrobial agents. Int J Food Microbiol 2003; 82: 1: 1-11.Danielsen M., Wind A. Susceptibility of Lactobacillus spp. to antimicrobial agents. Int J Food Microbiol 2003; 82: 1: 1-11.Ocana V., Silva C., Nader-Macias M.E. Antibiotic susceptibility of potentially probiotic vaginal lactobacilli. Infect Dis Obstet Gynecol. 2006; 2006: 18182. 18.Ocana V., Silva C., Nader-Macias M.E. Antibiotic susceptibility of potentially probiotic vaginal lactobacilli. Infect Dis Obstet Gynecol. 2006; 2006: 18182. 18.National Committee for Clinical Laboratory Standards (NCCLS). Performance standards for antimicrobial disk susceptibility tests. Approved standard M2-A6. Wayne, Pa: National Committee for Clinical Laboratory Standards; 1997.National Committee for Clinical Laboratory Standards (NCCLS). Performance standards for antimicrobial disk susceptibility tests. Approved standard M2-A6. Wayne, Pa: National Committee for Clinical Laboratory Standards; 1997.Charteris W.P., Kelly P.M., Morelli L., Collins J.K. Antibiotic susceptibility of potentially probiotic Lactobacillus species. J Food Prot 1998; 61: 12: 1636-1643.Charteris W.P., Kelly P.M., Morelli L., Collins J.K. Antibiotic susceptibility of potentially probiotic Lactobacillus species. J Food Prot 1998; 61: 12: 1636-1643.Kirtzalidou E., Pramateftaki P., Kotsou M., Kyriacou A. Screening for lactobacilli with probiotic properties in the infant gut microbiota. Anaerobe 2011; 17: 6: 440-443.Kirtzalidou E., Pramateftaki P., Kotsou M., Kyriacou A. Screening for lactobacilli with probiotic properties in the infant gut microbiota. Anaerobe 2011; 17: 6: 440-443.Wang C.Y., Lin P.R., Ng C.C., Shyu Y.T. Probiotic properties of Lactobacillus strains isolated from the feces of breast-fed infants and Taiwanese pickled cabbage. Anaerobe 2010; 16: 6: 578-585.Wang C.Y., Lin P.R., Ng C.C., Shyu Y.T. Probiotic properties of Lactobacillus strains isolated from the feces of breast-fed infants and Taiwanese pickled cabbage. Anaerobe 2010; 16: 6: 578-585.Katla A.K., Kruse H., Johnsen G., Herikstad H. Antimicrobial susceptibility of starter culture bacteria used in Norwegian dairy products. Int J Food Microbiol 2001; 67: 1-2: 147-152.Katla A.K., Kruse H., Johnsen G., Herikstad H. Antimicrobial susceptibility of starter culture bacteria used in Norwegian dairy products. Int J Food Microbiol 2001; 67: 1-2: 147-152.Rojo-Bezares B., Sáenz Y., Poeta P., Zarazaga M., Ruiz-Larrea F., Torres C. Assessment of antibiotic susceptibility within lactic acid bacteria strains isolated from wine. Int J Food Microbiol 2006; 111: 3: 234-240.Rojo-Bezares B., Sáenz Y., Poeta P., Zarazaga M., Ruiz-Larrea F., Torres C. Assessment of antibiotic susceptibility within lactic acid bacteria strains isolated from wine. Int J Food Microbiol 2006; 111: 3: 234-240.Gueimonde M., Sánchez B., G de Los Reyes-Gavilán C., Margolles A. Antibiotic resistance in probiotic bacteria. Front Microbiol 2013; 4: 202.Gueimonde M., Sánchez B., G de Los Reyes-Gavilán C., Margolles A. Antibiotic resistance in probiotic bacteria. Front Microbiol 2013; 4: 202.Klein G., Hallman C., Casas I.A., Abad J., Lowers J., Reuter G. Exclusion of vanA, vanB and vanC type glycopeptide resistance in strains of Lactobacillus reuteri and Lactobacillus rhamnosus used as probiotics by polymerase chain reaction and hybridization methods. J Appl Microbiol 2000; 89: 815-824.Klein G., Hallman C., Casas I.A., Abad J., Lowers J., Reuter G. Exclusion of vanA, vanB and vanC type glycopeptide resistance in strains of Lactobacillus reuteri and Lactobacillus rhamnosus used as probiotics by polymerase chain reaction and hybridization methods. J Appl Microbiol 2000; 89: 815-824.Saarela M., Mättö J., Mattila-Sandholm T. Safety aspects of Lactobacillus and Bifidobacterium species originating from human oro-gastrointestinal tract or from probiotic products. Microb Ecol Health Dis 2002; 14: 233-240.Saarela M., Mättö J., Mattila-Sandholm T. Safety aspects of Lactobacillus and Bifidobacterium species originating from human oro-gastrointestinal tract or from probiotic products. Microb Ecol Health Dis 2002; 14: 233-240.Ботина С.Г., Полуэктова Е.У., Глазова A.A., Захаревич Н.В., Коробан Н.В., Зинченко В.В., Бабыкин М.М., Жиленкова О.Г., Амерханова А.М., Даниленко В.Н. Характеристика устойчивости к антибиотикам по тенциальных пробиотических бактерий рода Lactobacillus из гастроинтестинальной микробиомы человека. Микробиология 2011; 80: 2: 1-9.Ботина С.Г., Полуэктова Е.У., Глазова A.A., Захаревич Н.В., Коробан Н.В., Зинченко В.В., Бабыкин М.М., Жиленкова О.Г., Амерханова А.М., Даниленко В.Н. Характеристика устойчивости к антибиотикам по тенциальных пробиотических бактерий рода Lactobacillus из гастроинтестинальной микробиомы человека. Микробиология 2011; 80: 2: 1-9.Davis B.D. Mechanism of bactericidal action of aminoglycosides. Microbiol Rev 1987; 51: 3: 341-350.Davis B.D. Mechanism of bactericidal action of aminoglycosides. Microbiol Rev 1987; 51: 3: 341-350.Malfertheiner P., Megraud F., O'Morain C.A., Atherton J., Axon A.T., Bazzoli F., Gensini G.F., Gisbert J.P., Graham D.Y., Rokkas T., El-Omar E.M., Kuipers E.J., European Helicobacter Study Group. Management of Helicobacter pylori infection - the Maastricht IV / Florence Consensus Report. Gut 2012; 61: 5: 646-664.Malfertheiner P., Megraud F., O'Morain C.A., Atherton J., Axon A.T., Bazzoli F., Gensini G.F., Gisbert J.P., Graham D.Y., Rokkas T., El-Omar E.M., Kuipers E.J., European Helicobacter Study Group. Management of Helicobacter pylori infection - the Maastricht IV / Florence Consensus Report. Gut 2012; 61: 5: 646-664.Sheu B.S., Cheng H.C., Kao A.W., Wang S.T., Yang Y.J., Yang H.B., Wu J.J. Pretreatment with Lactobacillus- and Bifidobacterium-containing yogurt can improve the efficacy of quadruple therapy in eradicating residual Helicobacter pylori infection after failed triple therapy. Am J Clin Nutr 2006; 83: 4: 864-869.Sheu B.S., Cheng H.C., Kao A.W., Wang S.T., Yang Y.J., Yang H.B., Wu J.J. Pretreatment with Lactobacillus- and Bifidobacterium-containing yogurt can improve the efficacy of quadruple therapy in eradicating residual Helicobacter pylori infection after failed triple therapy. Am J Clin Nutr 2006; 83: 4: 864-869.Deguchi R., Nakaminami H., Rimbara E., Noguchi N., Sasatsu M., Suzuki T., Matsushima M., Koike J., Igarashi M., Ozawa H., Fukuda R., Takagi A. Effect of pretreatment with Lactobacillus gasseri OLL2716 on first-line Helicobacter pylori eradication therapy. J Gastroenterol Hepatol 2012; 27: 5: 888-892.Deguchi R., Nakaminami H., Rimbara E., Noguchi N., Sasatsu M., Suzuki T., Matsushima M., Koike J., Igarashi M., Ozawa H., Fukuda R., Takagi A. Effect of pretreatment with Lactobacillus gasseri OLL2716 on first-line Helicobacter pylori eradication therapy. J Gastroenterol Hepatol 2012; 27: 5: 888-892.Pacifico L., Osborn J.F., Bonci E., Romaggioli S., Baldini R., Chiesa C. Probiotics for the treatment of Helicobacter pylori infection in children. World J Gastroenterol 2014; 20: 3: 673-683.Pacifico L., Osborn J.F., Bonci E., Romaggioli S., Baldini R., Chiesa C. Probiotics for the treatment of Helicobacter pylori infection in children. World J Gastroenterol 2014; 20: 3: 673-683.Lesbros-Pantoflickova D., Corthésy-Theulaz I., Blum A.L. Helicobacter pylori and probiotics // J Nutr. 2007; 137: 3: 812S-818S.Lesbros-Pantoflickova D., Corthésy-Theulaz I., Blum A.L. Helicobacter pylori and probiotics // J Nutr. 2007; 137: 3: 812S-818S.Sandberg-Gertzen H., Kjellander J., Sundberg-Gillå B., Järnerot G. In vitro effects of sulphasalazine, azodisal sodium, and their metabolites on Clostridium difficile and some other faecal bacteria. Scand J Gastroenterol 1985; 20: 5: 607-612.Sandberg-Gertzen H., Kjellander J., Sundberg-Gillå B., Järnerot G. In vitro effects of sulphasalazine, azodisal sodium, and their metabolites on Clostridium difficile and some other faecal bacteria. Scand J Gastroenterol 1985; 20: 5: 607-612.Kaufman J., Griffiths T.A., Surette M.G., Ness S., Rioux K.P. Effects of mesalamine (5-aminosalicylic acid) on bacterial gene expression. Inflamm Bowel Dis 2009; 15: 7: 985-996.Kaufman J., Griffiths T.A., Surette M.G., Ness S., Rioux K.P. Effects of mesalamine (5-aminosalicylic acid) on bacterial gene expression. Inflamm Bowel Dis 2009; 15: 7: 985-996.Greenstein R.J., Su L., Shahidi A., Brown S.T. On the action of 5-aminosalicylic acid and sulfapyridine on M.avium including subspecies paratuberculosis. PLoS One 2007; 2: 6: e516.Greenstein R.J., Su L., Shahidi A., Brown S.T. On the action of 5-aminosalicylic acid and sulfapyridine on M.avium including subspecies paratuberculosis. PLoS One 2007; 2: 6: e516.Swidsinski A., Loening-Baucke V., Bengmark S., Lochs H., Dörffel Y. Azathioprine and mesalazine-induced effects on the mucosal flora in patients with IBD colitis. Inflamm Bowel Dis 2007; 13: 1: 51-56.Swidsinski A., Loening-Baucke V., Bengmark S., Lochs H., Dörffel Y. Azathioprine and mesalazine-induced effects on the mucosal flora in patients with IBD colitis. Inflamm Bowel Dis 2007; 13: 1: 51-56.Rioux K.P., Bibiloni R., Tannock G.W., Dieleman L.A., Fedorak R.N. Aminosalicylates alter the dominant phylogenetic profile of fecal bacteria in mice. Gastroenterology 2005; 128: A663.Rioux K.P., Bibiloni R., Tannock G.W., Dieleman L.A., Fedorak R.N. Aminosalicylates alter the dominant phylogenetic profile of fecal bacteria in mice. Gastroenterology 2005; 128: A663.Andrews C.N., Griffiths T.A., Kaufman J., Vergnolle N., Surette M.G., Rioux K.P. Mesalazine (5-aminosalicylic acid) alters faecal bacterial profiles, but not mucosal proteolytic activity in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2011; 34: 3: 374-383.Andrews C.N., Griffiths T.A., Kaufman J., Vergnolle N., Surette M.G., Rioux K.P. Mesalazine (5-aminosalicylic acid) alters faecal bacterial profiles, but not mucosal proteolytic activity in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2011; 34: 3: 374-383.Williams C., Panaccione R., Ghosh S., Rioux K Optimizing clinical use of mesalazine (5-aminosalicylic acid) in inflammatory bowel disease. Therap Adv Gastroenterol 2011; 4: 4: 237-248.Williams C., Panaccione R., Ghosh S., Rioux K Optimizing clinical use of mesalazine (5-aminosalicylic acid) in inflammatory bowel disease. Therap Adv Gastroenterol 2011; 4: 4: 237-248.

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