Представления врачей-гастроэнтерологов о препаратах, модулирующих кишечную микробиоту: результаты исследования в фокус-группах

Головенко О.В., Головенко А.О. Представления врачей-гастроэнтерологов о препаратах, модулирующих кишечную микробиоту: результаты исследования в фокус-группах. Consilium Medicum. 2023;25(5):344–350. DOI: 10.26442/20751753.2023.5.202250

© ООО «КОНСИЛИУМ МЕДИКУМ», 2023 г.

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Golovenko OV, Golovenko AO. Opinions of gastroenterologists about intestinal microbiota modulating agents: results of the survey in focus groups. Consilium Medicum. 2023;25(5):344–350.
DOI: 10.26442/20751753.2023.5.202250

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Аннотация

Цель. Изучить представления гастроэнтерологов о препаратах, влияющих на кишечную микрофлору.
Материалы и методы. Для изучения паттернов назначения препаратов, регулирующих кишечную микрофлору, при хронических заболеваниях желудочно-кишечного тракта проведено качественное исследование в фокус-группах. В него включали только гастроэнтерологов амбулаторного звена, не менее 3 лет занимающихся практическим ведением пациентов с синдромом раздраженного кишечника, неосложненной дивертикулярной болезнью с клиническими проявлениями и избыточным бактериальным ростом в тонкой кишке.
Результаты. Врачи воспринимают неабсорбируемый антибиотик рифаксимин-альфа как основной препарат для лечения перечисленных заболеваний, они информированы о его низкой биодоступности и возможности повторного применения. В то же время при выраженных клинических симптомах часть врачей склонны назначать системные антибиотики до подтверждения гнойных или воспалительных осложнений. Это связано с ошибочным восприятием системных антибиотиков как заведомо более эффективных препаратов, чем неабсорбируемые антибиотики. При выборе препарата важно учитывать риск антибиотикоассоциированной диареи и негативных изменений микрофлоры, а также возможность назначения пациентам с сопутствующими заболеваниями.
Заключение. Опрошенные врачи-гастроэнтерологи считают рифаксимин альфа (Альфа Нормикс) наиболее подходящим препаратом, который помогает в рутинной практике достичь требуемого результата с минимальным риском нежелательных явлений. Многие участники исследования скептически относятся к эффекту пробиотиков в связи с отсутствием доказательной базы, но подчеркивают их безопасность и запрос на назначение пробиотиков, исходящий от пациентов. Не все врачи имеют представление о метабиотиках. Пребиотики, препараты пищевых волокон, воспринимаются как средства, воздействующие и на частоту стула, и на кишечную микрофлору. Часть специалистов обеспокоены регистрацией пребиотиков и пробиотиков в качестве биологически активных добавок, поскольку это может вызывать непонимание у пациентов. Выявленные представления о препаратах могут быть использованы при обучении гастроэнтерологов и разработке клинических рекомендаций.

Ключевые слова: кишечная микрофлора, неабсорбируемые антибиотики, рифаксимин, пробиотики, пребиотики, фокус-группы, психология врача

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A qualitative study was conducted in focus groups to study the patterns of prescribing drugs regulating intestinal microflora in chronic gastrointestinal diseases. Only outpatient gastroenterologists treating patients with irritable bowel syndrome, symptomatic uncomplicated diverticular disease and small bowel bacterial growth for at least 3 years were included. Doctors perceive non-absorbable antibiotics, predominantly -rifaximin-alpha, as main drugs in the mentioned diseases, are informed about the low bioavailability and the possibility of repeated use. At the same time, with pronounced clinical symptoms, some doctors prescribe systemic antibiotics without confirming of purulent or inflammatory complications. This is due to the mistaken perception of systemic antibiotics as inherently more effective drugs than non-absorbable antibiotics. The risk of antibiotic-associated diarrhea and general negative changes in the microflora, as well as the possibility of prescribing to patients with concomitant diseases, are important when choosing between antibiotics. Based on these factors, gastroenterologists consider rifaximin alpha (Alpha Normix) to be the most suitable drug that helps them in routine practice to achieve the desired result with minimal risk of adverse events. Participants are often skeptical about the effect of probiotics,) but emphasize their safety and the patients' demand for the prescription of probiotics. Not all doctors have an understanding of metabiotics. Prebiotics, dietary fibers, are perceived as means that affect both stool frequency and intestinal microflora. Some specialists are concerned about the registration of prebiotics and probiotics as dietary supplements, which may cause misunderstanding among patients. The identified views on drugs can be used in training gastroenterologists and developing clinical guidelines.

Keywords: intestinal microflora, non-absorbed antibiotics, rifaximin, probiotics, prebiotics, focus groups, doctor psychology

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Список литературы

1. Ianiro G, Bibbò S, Gasbarrini A, Cammarota G. Therapeutic modulation of gut microbiota: current clinical applications and future perspectives. Curr Drug Targets. 2014;15(8):762-770. doi: 10.2174/1389450115666140606111402
2. Bellini M, Tosetti C, Rettura F, et al. Translational Gap between Guidelines and Clinical Medicine: The Viewpoint of Italian General Practitioners in the Management of IBS. J Clin Med. 2022;11(13):3861. Published 2022 Jul 3. doi: 10.3390/jcm11133861
3. Renjith V, Yesodharan R, Noronha JA, et al. Qualitative Methods in Health Care Research. Int J Prev Med. 2021;12:20. Published 2021 Feb 24. doi: 10.4103/ijpvm.IJPVM_321_19
4. Anderson C. Presenting and evaluating qualitative research. Am J Pharm Educ. 2010;74(8):141. doi: 10.5688/aj7408141
5. Rustom LBO, Sharara AI. The Natural History of Colonic Diverticulosis: Much Ado about Nothing?. Inflamm Intest Dis. 2018;3(2):69-74. doi: 10.1159/000490054
6. Ардатская М.Д., Ачкасов С.И., Веселов В.В. с соавт. Клинические рекомендации. Дивертикулярная болезнь. Колопроктология. 2021;20(3):10-27.
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8. Krogsgaard LR, Engsbro AL, Bytzer P. Antibiotics: a risk factor for irritable bowel syndrome in a population-based cohort. Scand J Gastroenterol. 2018;53(9):1027-1030. doi: 10.1080/00365521.2018.1500638
9. Vinelli V, Biscotti P, Martini D, et al. Effects of Dietary Fibers on Short-Chain Fatty Acids and Gut Microbiota Composition in Healthy Adults: A Systematic Review. Nutrients. 2022;14(13):2559. doi: 10.3390/nu14132559
10. Dixon-Woods M, Critchley S. Medical and lay views of irritable bowel syndrome. Fam Pract. 2000;17(2):108-113. doi: 10.1093/fampra/17.2.108
11. Pace F, Molteni P, Bollani S, et al. Inflammatory bowel disease versus irritable bowel syndrome: a hospital-based, case-control study of disease impact on quality of life. Scand J Gastroenterol. 2003;38(10):1031-1038. doi:10.1080/00365520310004524
12. Tursi A, Franceschi M, Elisei W, et al. The natural history of symptomatic uncomplicated diverticular disease: a long-term follow-up study. Ann Gastroenterol. 2021;34(2):208-213. doi: 10.20524/aog.2020.0560
13. Ивашкин В.Т., Маев И.В., Шелыгин Ю.А. с соавт. Диагностика и лечение синдрома раздраженного кишечника (Клинические рекомендации Российской гастроэнтерологической ассоциации и Ассоциации колопроктологов России). Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2021;31(5):74-95. doi.org/ 10.22416/1382-4376-2021-31-5-74-95 Ivashkin V.T., Maev I.V., Shelygin Yu.A., et al. Diagnosis and Treatment of Irritable Bowel Syndrome: Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2021;31(5):74-95. (In Russ.)
14. Vasant DH, Paine PA, Black CJ, et al. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut. 2021;70(7):1214-1240.
doi: 10.1136/gutjnl-2021-324598
15. Li J, Zhu W, Liu W. et al. Rifaximin for Irritable Bowel Syndrome: A Meta-Analysis of Randomized Placebo-Controlled Trials. Medicine (Baltimore). 2016;95(4):e2534. doi: 10.1097/MD.0000000000002534
16. Bianchi M, Festa V, Moretti A, et al. Meta-analysis: long-term therapy with rifaximin in the management of uncomplicated diverticular disease. Aliment Pharmacol Ther. 2011;33(8):902-910. doi: 10.1111/j.1365-2036.2011.04606.x
17. Calanni F, Renzulli C, Barbanti M, Viscomi GC. Rifaximin: beyond the traditional antibiotic activity. J Antibiot (Tokyo). 2014;67(9):667-670. doi: 10.1038/ja.2014.106
18. Descombe JJ, Dubourg D, Picard M, Palazzini E. Pharmacokinetic study of rifaximin after oral administration in healthy volunteers. Int J Clin Pharmacol Res. 1994;14(2):51-56.
19. Wang Y, Chen N, Niu F, et al. Probiotics therapy for adults with diarrhea-predominant irritable bowel syndrome: a systematic review and meta-analysis of 10 RCTs. Int J Colorectal Dis. 2022;37(11):2263-2276. doi: 10.1007/s00384-022-04261-0
20. van der Geest AM, Schukking I, Brummer RJM, van de Burgwal LHM, Larsen OFA. Comparing probiotic and drug interventions in irritable bowel syndrome: a meta-analysis of randomised controlled trials. Benef Microbes. 2022;13(3):183-194. doi: 10.3920/BM2021.0123
21. Asha MZ, Khalil SFH. Efficacy and Safety of Probiotics, Prebiotics and Synbiotics in the Treatment of Irritable Bowel Syndrome: A systematic review and meta-analysis. Sultan Qaboos Univ Med J. 2020;20(1):e13-e24. doi:10.18295/squmj.2020.20.01.003
22. Pimentel M, Chow EJ, Lin HC. Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. A double-blind, randomized, placebo-controlled study. Am J Gastroenterol. 2003;98:412–419.
23. Yang, J., Lee, HR., Low, K. et al. Rifaximin versus Other Antibiotics in the Primary Treatment and Retreatment of Bacterial Overgrowth in IBS. Dig Dis Sci 53, 169–174 (2008). doi: 10.1007/s10620-007-9839-8
24. Ponziani FR, Zocco MA, D'Aversa F, Pompili M, Gasbarrini A. Eubiotic properties of rifaximin: Disruption of the traditional concepts in gut microbiota modulation. World J Gastroenterol. 2017;23(25):4491-4499. doi: 10.3748/wjg.v23.i25.4491
25. Soldi S, Vasileiadis S, Uggeri F, et al. Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach. Clin Exp Gastroenterol. 2015;8:309-325. Published 2015 Dec 4. doi: 10.2147/CEG.S89999
26. Ponziani FR, Scaldaferri F, Petito V, et al. The Role of Antibiotics in Gut Microbiota Modulation: The Eubiotic Effects of Rifaximin. Dig Dis. 2016;34(3):269-278. doi: 10.1159/000443361
27. Blandizzi C, Viscomi GC, Scarpignato C. Impact of crystal polymorphism on the systemic bioavailability of rifaximin, an antibiotic acting locally in the gastrointestinal tract, in healthy volunteers. Drug Des Devel Ther. 2014;9:1-11. Published 2014 Dec 16. doi: 10.2147/DDDT.S72572
28. Blandizzi C, Viscomi GC, Marzo A, Scarpignato C. Is generic rifaximin still a poorly absorbed antibiotic? A comparison of branded and generic formulations in healthy volunteers. Pharmacol Res. 2014;85:39-44. doi: 10.1016/j.phrs.2014.05.001
29. El-Salhy M, Ystad SO, Mazzawi T, Gundersen D. Dietary fiber in irritable bowel syndrome (Review). Int J Mol Med. 2017;40(3):607-613. doi:10.3892/ijmm.2017.3072
30. Furnari M, Parodi A, Gemignani L, et al. Clinical trial: the combination of rifaximin with partially hydrolysed guar gum is more effective than rifaximin alone in eradicating small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2010;32(8):1000-1006. doi: 10.1111/j.1365-2036.2010.04436.x

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1. Ianiro G, Bibbò S, Gasbarrini A, Cammarota G. Therapeutic modulation of gut microbiota: current clinical applications and future perspectives. Curr Drug Targets. 2014;15(8):762-770. doi: 10.2174/1389450115666140606111402
2. Bellini M, Tosetti C, Rettura F, et al. Translational Gap between Guidelines and Clinical Medicine: The Viewpoint of Italian General Practitioners in the Management of IBS. J Clin Med. 2022;11(13):3861. Published 2022 Jul 3. doi: 10.3390/jcm11133861
3. Renjith V, Yesodharan R, Noronha JA, et al. Qualitative Methods in Health Care Research. Int J Prev Med. 2021;12:20. Published 2021 Feb 24. doi: 10.4103/ijpvm.IJPVM_321_19
4. Anderson C. Presenting and evaluating qualitative research. Am J Pharm Educ. 2010;74(8):141. doi: 10.5688/aj7408141
5. Rustom LBO, Sharara AI. The Natural History of Colonic Diverticulosis: Much Ado about Nothing?. Inflamm Intest Dis. 2018;3(2):69-74. doi: 10.1159/000490054
6. Ardatskaya MD, Achkasov SI, Veselov VV., et al. Clinical recommendations. Diverticular Disease. Coloproctology. 2021;20(3):10-27. (In Russ.)
7. Pimentel M, Saad RJ, Long MD, Rao SSC. ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth. Am J Gastroenterol. 2020;115(2):165-178. doi: 10.14309/ajg.0000000000000501
8. Krogsgaard LR, Engsbro AL, Bytzer P. Antibiotics: a risk factor for irritable bowel syndrome in a population-based cohort. Scand J Gastroenterol. 2018;53(9):1027-1030. doi: 10.1080/00365521.2018.1500638
9. Vinelli V, Biscotti P, Martini D, et al. Effects of Dietary Fibers on Short-Chain Fatty Acids and Gut Microbiota Composition in Healthy Adults: A Systematic Review. Nutrients. 2022;14(13):2559. doi: 10.3390/nu14132559
10. Dixon-Woods M, Critchley S. Medical and lay views of irritable bowel syndrome. Fam Pract. 2000;17(2):108-113. doi: 10.1093/fampra/17.2.108
11. Pace F, Molteni P, Bollani S, et al. Inflammatory bowel disease versus irritable bowel syndrome: a hospital-based, case-control study of disease impact on quality of life. Scand J Gastroenterol. 2003;38(10):1031-1038. doi:10.1080/00365520310004524
12. Tursi A, Franceschi M, Elisei W, et al. The natural history of symptomatic uncomplicated diverticular disease: a long-term follow-up study. Ann Gastroenterol. 2021;34(2):208-213. doi: 10.20524/aog.2020.0560
13. Ivashkin V.T., Maev I.V., Shelygin Yu.A., et al. Diagnosis and Treatment of Irritable Bowel Syndrome: Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2021;31(5):74-95. (In Russ.)
14. Vasant DH, Paine PA, Black CJ, et al. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut. 2021;70(7):1214-1240.
doi: 10.1136/gutjnl-2021-324598
15. Li J, Zhu W, Liu W. et al. Rifaximin for Irritable Bowel Syndrome: A Meta-Analysis of Randomized Placebo-Controlled Trials. Medicine (Baltimore). 2016;95(4):e2534. doi: 10.1097/MD.0000000000002534
16. Bianchi M, Festa V, Moretti A, et al. Meta-analysis: long-term therapy with rifaximin in the management of uncomplicated diverticular disease. Aliment Pharmacol Ther. 2011;33(8):902-910. doi: 10.1111/j.1365-2036.2011.04606.x
17. Calanni F, Renzulli C, Barbanti M, Viscomi GC. Rifaximin: beyond the traditional antibiotic activity. J Antibiot (Tokyo). 2014;67(9):667-670. doi: 10.1038/ja.2014.106
18. Descombe JJ, Dubourg D, Picard M, Palazzini E. Pharmacokinetic study of rifaximin after oral administration in healthy volunteers. Int J Clin Pharmacol Res. 1994;14(2):51-56.
19. Wang Y, Chen N, Niu F, et al. Probiotics therapy for adults with diarrhea-predominant irritable bowel syndrome: a systematic review and meta-analysis of 10 RCTs. Int J Colorectal Dis. 2022;37(11):2263-2276. doi: 10.1007/s00384-022-04261-0
20. van der Geest AM, Schukking I, Brummer RJM, van de Burgwal LHM, Larsen OFA. Comparing probiotic and drug interventions in irritable bowel syndrome: a meta-analysis of randomised controlled trials. Benef Microbes. 2022;13(3):183-194. doi: 10.3920/BM2021.0123
21. Asha MZ, Khalil SFH. Efficacy and Safety of Probiotics, Prebiotics and Synbiotics in the Treatment of Irritable Bowel Syndrome: A systematic review and meta-analysis. Sultan Qaboos Univ Med J. 2020;20(1):e13-e24. doi:10.18295/squmj.2020.20.01.003
22. Pimentel M, Chow EJ, Lin HC. Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. A double-blind, randomized, placebo-controlled study. Am J Gastroenterol. 2003;98:412–419.
23. Yang, J., Lee, HR., Low, K. et al. Rifaximin versus Other Antibiotics in the Primary Treatment and Retreatment of Bacterial Overgrowth in IBS. Dig Dis Sci 53, 169–174 (2008). doi: 10.1007/s10620-007-9839-8
24. Ponziani FR, Zocco MA, D'Aversa F, Pompili M, Gasbarrini A. Eubiotic properties of rifaximin: Disruption of the traditional concepts in gut microbiota modulation. World J Gastroenterol. 2017;23(25):4491-4499. doi: 10.3748/wjg.v23.i25.4491
25. Soldi S, Vasileiadis S, Uggeri F, et al. Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach. Clin Exp Gastroenterol. 2015;8:309-325. Published 2015 Dec 4. doi: 10.2147/CEG.S89999
26. Ponziani FR, Scaldaferri F, Petito V, et al. The Role of Antibiotics in Gut Microbiota Modulation: The Eubiotic Effects of Rifaximin. Dig Dis. 2016;34(3):269-278. doi: 10.1159/000443361
27. Blandizzi C, Viscomi GC, Scarpignato C. Impact of crystal polymorphism on the systemic bioavailability of rifaximin, an antibiotic acting locally in the gastrointestinal tract, in healthy volunteers. Drug Des Devel Ther. 2014;9:1-11. Published 2014 Dec 16. doi: 10.2147/DDDT.S72572
28. Blandizzi C, Viscomi GC, Marzo A, Scarpignato C. Is generic rifaximin still a poorly absorbed antibiotic? A comparison of branded and generic formulations in healthy volunteers. Pharmacol Res. 2014;85:39-44. doi: 10.1016/j.phrs.2014.05.001
29. El-Salhy M, Ystad SO, Mazzawi T, Gundersen D. Dietary fiber in irritable bowel syndrome (Review). Int J Mol Med. 2017;40(3):607-613. doi:10.3892/ijmm.2017.3072
30. Furnari M, Parodi A, Gemignani L, et al. Clinical trial: the combination of rifaximin with partially hydrolysed guar gum is more effective than rifaximin alone in eradicating small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2010;32(8):1000-1006. doi: 10.1111/j.1365-2036.2010.04436.x

Авторы

О.В. Головенко1, А.О. Головенко*2

1 ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия;
2 ООО «Медсанчасть №14», Москва, Россия
*golovenkoao@gmail.com

________________________________________________

Oleg V. Golovenko1, Alexey O. Golovenko*2

1 Russian Medical Academy of Continuous Professional Education, Moscow, Russia;
2 Medical unit №14, Moscow, Russia
*golovenkoao@gmail.com

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