Türkiye’de akut ishalli çocuklarda Lactobacillus rhamnosus LGG ve Bifidobacterium animalis subspecies lactis BB-12 kombinasyonunun ishal ve hastanede yatış süresi üzerine etkisi

Year 2020, , 34 - 41, 30.06.2020

Ener Cagri Dınleyıcı , Metehan Ozen , Nazan Dalgıç Olcay Yasa Vefik Arıca , Ozge Metin , Gönül Tanır , Zafer Kurugol , Şirin Güven , Ahmet Sami Yazar , Adem Karbuz , Burcin Nalbantoglu Mesut Sancar , Makbule Eren , Ateş Kara , Yvan Vandenplas

https://doi.org/10.33204/mucosa.738326

Abstract

Amaç Akut ishal tüm dünyada en önemli morbidite ve mortalite nedenleri arasında yer almaktadır. İshal nedeni ile başvuran tüm hastalarda, dehidratasyonun temel tedavisi oral rehidratasyon sıvısıdır. Probiyotikler, akut ishal destek tedavi seçenekleri arasında yer almaktadır. Bu çalışmanın amacı akut ishali olan çocuklarda Lactobacillus rhamnosus GG (LGG) ve Bifidobacterium animalis subspecies lactis BB-12 (BB-12) kombinasyonun ishal süresi ve hastanede yatış süresi üzerine etkisinin değerlendirilmesidir.

Yöntem Bu çok merkezli, randomize (240 çocuk, probiyotik ile kontrol 2:1 randomizasyon), tek kör çalışma, akut ishal yakınmalarının başlamasından 24-72 saat içerisinde hastaneye başvuran, yaşları 6 ay ile 60 ay arasında değişen çocuklarda yapıldı. Çalışmaya hafif ve orta derecede dehidratasyonu olan çocuklar dahil edildi. Çalışmaya dahil edilen çocuklarda, kontrol grubu standart tedavi alırken, probiyotik grubu 5 gün süre ile LGG ve BB-12 (her bir probiyotik 1×109 koloni) kombinasyonu aldı. Çalışmanın primer sonlanım noktası olarak ishal süresinin Bristol gayta skoru ile takip edilmesi planlandı. Sekonder sonlanım noktası ise hastanede yatış süresi (gün) ve 72. saatin sonunda ishal tablosu gerileyen çocuk yüzdesi olarak belirlendi.

Bulgular Çalışmaya katılan 240 çocuğun 218’nin (probiyotik grubunda 150 çocuk, kontrol grubunda 68 çocuk) verileri değerlendirildi. LGG ve BB-12 grubunda ishal süresinin kontrol grubuna göre anlamlı derecede düşük olduğu saptandı (sırası ile 74.5 ± 40.8 saat, 98.4 ± 22.9 saat, P<0.001). Çalışmanın 72.saatinde ishal tablosu gerileyen çocuk yüzdesi LGG ve BB-12 grubunda kontrol grubuna göre belirgin yüksek olduğu saptandı (%60 vs. %33.8, P<0.001). Ortalama hastanede yatış süresi gruplar arasında benzer olarak bulundu (5.03 ± 2.3 gün vs. 5.25 ± 1.3 gün, P>0.05).

Sonuç LGG ve BB-12 kombinasyonun akut ishal olgularında ilk kez değerlendirildiği bu çalışmada,ishal süresi üzerine olumlu etkilerinin olduğu gösterildi. Hastaneye yatan çocuklarda ishal süresinin yaklaşık 24 saat kısaldığı saptandı. Hastaneye yatan çocuklara ek olarak, akut ishal nedeni ile poliklinik başvurusu yapan çocuklarda yapılacak randomize klinik çalışmalar ile bu kombinasyonun etkisi daha detaylı değerlendirilmelidir.

Keywords

probiyotik, LGG, BB-12, ishal, hastaneye yatış, gastroenterit, Lactobacillus rhamnosus, Lacticaseibacillus rhamnosus

Effect of Lactobacillus rhamnosus LGG and Bifidobacterium animalis subspecies lactis BB-12 combination on the duration of diarrhea and length of hospital stay in children with acute diarrhea in Turkey

Abstract

Background Acute diarrhea continues to be a leading cause of morbidity and mortality worldwide. The main therapy for all individuals with dehydration caused by diarrhea is oral rehydration. Probiotics have been proposed as a complementary therapy in the treatment of acute diarrhea. We aim to evaluate the effect of a combination of Lactobacillus rhamnosus GG (LGG) with Bifidobacterium animalis subspecies lactis BB-12 (BB-12) on the duration of diarrhea and length of hospital stay in children with acute diarrhea.

Methods A multicenter, randomized (240 children, 2:1 randomized for probiotic vs. control), single blind, hospital based clinical trial was performed in children (6 to 60 months) with acute watery diarrhea lasting more than 24 but less than 72 hours, requiring hospitalization. We enrolled children with clinical signs of mild to moderate dehydration. The children received conventional therapy with or without the combination of LGG and BB-12 (1 × 109 colony forming units for each) for 5 days. The primary endpoint was the duration of diarrhea (in hours), defined as the first normal stool according to the Bristol stool score (score < 5). Secondary outcome measures were duration of hospitalization (days) and percentage of children without diarrhea at 72 hours of intervention.

Results In total, data from 218 of 240 children could be evaluated (150 in the probiotic group and 68 in the control group). The duration of diarrhea was significantly reduced in the LGG and BB-12 group compared to the control group (74.5 ± 40.8 hours vs. 98.4 ± 22.9 hours, P<0.001). The percentage of diarrhea-free children was significantly larger in the LGG and BB-12 group at 72 hours compared to the control (60% vs. 33.8%, P<0.001). Mean length of hospital stay was similar for both groups (5.03 ± 2.3 days vs. 5.25 ± 1.3 days, P>0.05).

Conclusion This is the first clinical trial to test the combination of LGG and BB-12, and show its effects on diarrhea duration in children with acute infectious diarrhea. The duration of diarrhea was reduced by approximately 24 hours in the hospitalized children. Further randomized controlled clinical trials including outpatient cases with acute infectious diarrhea in addition to hospitalized cases should be conducted to assess the potential effects of the combination in more detail.

Keywords

probiotics, LGG, BB-12, diarrhea, hospitalization, gastroenteritis, Lactobacillus rhamnosus, Lacticaseibacillus rhamnosus

References

• 1. Global burden of disease 2013 mortality and causes of death collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015;385:117-71.
• 2. Florez ID, Nino-Serna LF, Beltran-Arroyave CP. Acute infectious diarrhea and gastroenteritis in children. Curr Infect Dis Rep 2020;22:4.
• 3. Churgay CA, Aftab Z. Gastroenteritis in children: Part II. Prevention and management. Am Fam Physician 2012;85:1066-70.
• 4. Guarino A, Ashkenazi S, Gendrel D, Lo Vecchio A, Shamir R, Szajewska H European society for pediatric gastroenterology, hepatology, and nutrition; European society for pediatric infectious diseases. European society for pediatric gastroenterology, hepatology, and nutrition/European society for pediatric infectious diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe: update 2014. J Pediatr Gastroenterol Nutr 2014;59:132-52.
• 5. Vandenplas Y. Probiotics and prebiotics in infectious gastroenteritis. Best Pract Res Clin Gastroenterol 2016;30:49-53.
• 6. Hojsak I, Fabiano V, Pop TL, et al. Guidance on the use of probiotics in clinical practice in children with selected clinical conditions and in specific vulnerable groups. Acta Paediatr 2018;107:927-37.
• 7. McFarland LV. Deciphering meta-analytic results: a mini-review of probiotics for the prevention of paediatric antibiotic-associated diarrhoea and Clostridium difficile infections. Benef Microbes 2015;6:189-94.
• 8. Kolacek S, Hojsak I, Berni Canani R, et al. ESPGHAN working group for probiotics and prebiotics. Commercial probiotic products: A call for improved quality control. A position paper by the ESPGHAN working group for probiotics and prebiotics. J Pediatr Gastroenterol Nutr 2017;65:117-24.
• 9. Dinleyici EC, Kara A, Dalgic N, et al. Saccharomyces boulardii CNCM I-745 reduces the duration of diarrhoea, length of emergency care and hospital stay in children with acute diarrhoea. Benef Microbes 2015;6:415-21.
• 10. Szajewska H, Hojsak I. Health benefits of Lactobacillus rhamnosus GG and Bifidobacterium animalis subspecies lactisBB-12 in children. Postgrad Med 2020;26:1-11.
• 11. Van Niel C, Feudtner C, Garrison MM, Christakis DA. Lactobacillus therapy for acute infectious diarrhea in children: a meta-analysis. Pediatrics 2002;109:678-84.
• 12. Szajewska H, Kolodziej M, Gieruszczak-Bialek D, Skorka A, Ruszczynski M, Shamir R. Systematic review with meta-analysis: Lactobacillus rhamnosus GG for treating acute gastroenteritis in children - a 2019 update. Aliment Pharmacol Ther 2019;49:1376-84.
• 13. Szajewska H, Skorka A, Ruszczynski M, Gieruszczak-Bialek D. Meta-analysis: Lactobacillus GG for treating acute gastroenteritis in children-updated analysis of randomised controlled trials. Aliment Pharmacol Ther 2013;38:467-76.
• 14. Schnadower D, Tarr PI, Casper TC, et al. Lactobacillus rhamnosus GG versus placebo for acute gastroenteritis in children. N Engl J Med 2018;379:2002-14.
• 15. Vandenplas Y, De Hert SG, PROBIOTICAL-study group. Randomised clinical trial: the synbiotic food supplement Probiotical vs. placebo for acute gastroenteritis in children. Aliment Pharmacol Ther 2011;34:862-7.
• 16. Szajewska H, Skorka A, Ruszczynski M, Gieruszczak-Bialek D. Meta-analysis: Lactobacillus GG for treating acute diarrhoea in children. Aliment Pharmacol Ther 2007; 25:871-81.
• 17. Li YT, Xu H, Ye JZ, et al. Efficacy of Lactobacillus rhamnosus GG in treatment of acute pediatric diarrhea: A systematic review with meta-analysis. World J Gastroenterol 2019;25:4999-5016.
• 18. Cruchet S, Furnes R, Maruy A, et al. The use of probiotics in pediatric gastroenterology: a review of the literature and recommendations by Latin-American experts. Paediatr Drugs 2015;17:199-216.
• 19. Floch MH, Walker WA, Madsen K, et al. Recom mendations for probiotic use-2011 update. J Clin Gastroenterol 2011;45 Suppl:168-71.
• 20. World gastroenterology global guidelines. Probiotics and prebiotics. February 2017. https://www.worldgastroenterology.org/UserFiles/file/guidelines/probiotics-and-prebiotics-english-2017.pdf. (Last Access: 15 May 2020).
• 21. Zheng J, Wittouck S, Salvetti E, et al. A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillu Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. Int J Syst Evol Microbiol 2020. doi: 10.1099/ijsem.0.004107.
• 22. Dinleyici EC, PROBAGE Study Group, Vandenplas Y. Lactobacillus reuteri DSM 17938 effectively reduces the duration of acute diarrhoea in hospitalised children. Acta Paediatr 2014;103:e300-5.
• 23. Dinleyici EC, Dalgic N, Guven S, et al. Lactobacillus reuteri DSM 17938 shortens acute infectious diarrhea in a pediatric outpatient setting. J Pediatr (Rio J) 2015;91:392-6.
• 24. Dinleyici EC, Dalgic N, Guven S, et al. The effect of a multispecies synbiotic mixture on the duration of diarrhea and length of hospital stay in children with acute diarrhea in Turkey: single blinded randomized study. Eur J Pediatr 2013;172:459-64.
• 25. Dinleyici EC, Eren M, Yargic ZA, Vandenplas Y. Cost-effectiveness of add-on probiotics (Saccharomyces boulardii) in children with acute rotavirus diarrhea in Turkey (SB-cosTR). 44th annual meeting of the European society for paediatric gastroenterology, hepatology, and nutrition, 25-28 May 2011, Sorrento, Italy, Poster no: PO-G-0085.
• 26. Dinleyici EC, Kara A, Ozen M, et al. Cost analysis of Lactobacillus reuteri DSM 17938 in children with acute infectious gastroenteritis (PROBAGE Study). J Pediatr Gastroenterol Nutr 2017;64(Suppl 1):432.
• 27. do Carmo MS , Santos CID , Araujo MC , Giron JA , Fernandes ES , Monteiro-Neto V . Probiotics, mechanisms of action, and clinical perspectives for diarrhea management in children. Food Funct 2018;9:5074-95.
• 28. Dinleyici EC, Martinez-Martinez D, Kara A, et al. Time series analysis of the microbiota of children suffering from acute infectious diarrhea and their recovery after treatment. Front Microbiol 2018;9:1230.