Journal of IMAB - Annual Proceeding (Scientific Papers)
Publisher: Peytchinski, Gospodin Iliev
ISSN: 1312 773X (Online)
Issue: 2015, vol. 21, issue 4
Subject Area: Medicine - Pediatrics
Pages: 895-900
DOI: 10.5272/jimab.2015214.895
Published online: 07 October 2015

J of IMAB 2015 Oct-Dec;21(4):895-900
Miglena Georgieva1, Ruzha Pancheva2Corresponding Autor, Niya Rasheva1, Nataliya Usheva3, Liliya Ivanova4, Krassimira Koleva1,
1) Second Pediatric Clinic, University Hospital „St. Marina”, Varna, Bulgaria.
2) Department of Hygiene, Medical University, Varna, Bulgaria.
3) Department of Social medicine, Medical University, Varna, Bulgaria.
4) Virology laboratory, University Hospital „St. Marina”, Varna, Bulgaria.

Objective: To evaluate the effectiveness of Lactobacillus reuteri DSM 17938 for the prevention of antibiotic-associated diarrhoea and Clostridium difficile-related infections in hospitalized children in a Bulgarian hospital.
Study design: Children (n=100, aged 3 to 12 years) admitted to the hospital for acute infections were enrolled in a randomized, double- blind, placebo-controlled trial. They were assigned to receive either a probiotic supplement containing 1 x 108 CFU Lactobacillus reuteri DSM 17938 in the form of one chewable tablet once per day (n=49) (BioGaia AB, Stockholm, Sweden) or placebo (n=48). The probiotic or placebo was taken 2 hours after lunch each day, during the entire period of antibiotic treatment at the hospital and for additional 7 days.
Results: Data from 97 children were included in the final analysis. The incidence of diarrhoea (defined as at least 3 loose or watery stools per day in a 48-hour period that occurred during or up to 21 days after cessation of antibiotic treatment) was unexpectedly low in both groups - L. reuteri (n=1) versus placebo (n=1): 2,04 vs. 2,1 per 100 (p>0,05, risk ratio 1,02, 95% CI 0,7-1,4). L reuteri DSM 17938 did not significantly affect the incidence or severity of AAD diarrhoea and Clostridium difficile infection. We found unusually high colonisation rate of non-symptomatic C. difficile measured by toxin-specific ELISA. There was no difference between the probiotic and placebo groups for any of the other secondary outcomes (i.e., incidence of mild diarrhoea, frequency of stool samples positive for C. difficile toxin A and B at the beginning and at the end of study period, frequencies of other gastrointestinal symptoms in the same study period) (p<0,05). No adverse events were reported.
Conclusion: Due to the low incidence of antibiotic-associated diarrhoea in both groups, no conclusion can be made on the efficacy of L. reuteri DSM 17938 on AAD in hospitalized Bulgarian children. The probiotic did not affect the non-symptomatic high rate of C. difficile colonisation (33.3% in the placebo and 38.8% in the L. reuteri group at baseline) in this population. There was also no difference between groups regarding different gastrointestinal side effects.

Key words: Probiotic, Lactobacillus reuteri, Clostridium difficile, antibiotic associated diarrhoea, childhood,

- Download FULL TEXT /PDF 511 KB/
Please cite this article in PubMed Style or AMA (American Medical Association) Style:
Georgieva M, Pancheva R, Rasheva N, Usheva N, Ivanova L, Koleva K. Use of the probiotic Lactobacillus reuteri DSM 17938 in the prevention of antibiotic-associated infections in hospitalized Bulgarian children: a randomized, controlled trial. J of IMAB. 2015 Oct-Dec;21(4):895-900.

Correspondence to: Assoc. Prof. Ruzha Pancheva, Department of Hygiene, Disaster medicine and Epidemiology, Medical University of Varna; E-mail:

1. Bartlett JG. Clinical practice. Antibiotic-associated diarrhea. N Engl J Med. 2002 Jan 31;346(5):334-339. [PubMed] [CrossRef]
2. 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(2):189-94. [PubMed] [CrossRef]
3. Turck, D, Bernet JP, 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 Jul;37(1):22-26. [PubMed]
4. McFarland LV. Antibiotic-associated diarrhea: epidemiology, trends and treatment. Future Microbiol. 2008 Oct;3(5):563-578. [PubMed] [CrossRef]
5. Wiström J, Norrby SR, Myhre EB, Eriksson S, Grankström G, Lagergren L, et al. Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients: a prospective study. J Antimicrob Chemother. 2001 Jan;47(1):43-50. [PubMed] [CrossRef]
6. Bishara J, Peled N, Pitlik S, Samra Z. Mortality of patients with antibiotic-associated diarrhoea: the impact of Clostridium difficile. J Hosp Infect. 2008 Apr;68(4):308-314. [PubMed] [CrossRef]
7. Britton RA, Young VB. Interaction between the intestinal microbiota and host in Clostridium difficile colonization resistance. Trends Microbiol. 2012 Jul;20(7):313-319. [PubMed] [CrossRef]
8. Young VB, Schmidt TM. Antibiotic-associated diarrhea accompanied by large-scale alterations in the composition of the fecal microbiota.J Clin Microbiol.  2004 Mar;42(3):1203-1206. [PubMed] [CrossRef]
9. Schutze GE, Willoughby RE, Committee on Infectious Diseases American Academy of Pediatrics. Clostridium difficile infection in infants and children. Pediatrics. 2013 Jan;131(1):196-200. [PubMed] [CrossRef]
10. Zilberberg MD, Shorr AF, Kollef MH. Increase in adult Clostridium difficile–related hospitalizations and case-fatality rate, United States, 2000–2005. Emerg Infect Dis. 2008 Jun;14(6):929-931. [PubMed] [CrossRef]
11. Cryan JF, O’Mahony SM. The microbiome-gut-brain axis: from bowel to behavior. J Neurogastroenterol Motil. 2011 Mar;23(3):187-192. [PubMed] [CrossRef]
12. Maxwell PR, Rink E, Kumar D, Mendall MA. Antibiotics increase functional abdominal symptoms. Am J Gastroenterol. 2002 Jan;97(1):104-108. [PubMed] [CrossRef]
13. Svedlund J, Sjödin I, Dotevall G. GSRS-a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci.1988 Feb;33(2):129-134. [PubMed]
14. Hempel S, Newberry SJ, Maher AR, Wang Z, Miles JN, Shanman R, et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA.2012 May;307(18):1959-1969. [PubMed] [CrossRef]
15. Szajewska H, Wanke M, Patro B. Meta analysis: the effects of Lactobacillus rhamnosus GG supplementation for the prevention of healthcare associated diarrhoea in children. Aliment Pharmacol Ther. 2011 Nov;34(9):1079-1087. [PubMed] [CrossRef]
16. Wanke M, Szajewska H. Probiotics for preventing healthcare-associated diarrhea in children: A meta-analysis of randomized controlled trials. Pediatria Polska. 2014 Jan-Feb;89(1):8-16. [CrossRef]
17. Guarino, A., Winter, H., Sandhu, B., Quak SH, Lanata C. Acute gastroenteritis disease: Report of the FISPGHAN Working Group. J Pediatr Gastroenterol Nutr.2012 Nov;55(5):621-626. [PubMed] [CrossRef]
18. Szajewska H, Guarino A, Hojsak, I, Indrio F, Kolacek S, Shamir R, et al. Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr. 2014 Apr;58(4):531-539. [PubMed] [CrossRef]
19. Redelings MD, Sorvillo F, Mascola L. Increase in& Clostridium difficile-related mortality rates, United States, 1999–2004. Emerg Infect Dis. 2007 Sep;13(9):1417-9. [PubMed] [CrossRef]
20. Burckhardt F, Friedrich A, Beier D, Eckmanns T. Clostridium difficile surveillance trends, Saxony, Germany. Emerg Infect Dis. 2008 Apr;14(4):691-2. [PubMed] [CrossRef]
21. Gravel D, Miller M, Simor A, Taylor G, Gardam M, McGeer A, et al. Health care-associated Clostridium difficile infection in adults admitted to acute care hospitals in Canada: a Canadian Nosocomial Infection Surveillance Program study. Clin Infect Dis. 2009 Mar 1;48(5):568-76. [PubMed] [CrossRef]
22. Abrahamsson TR, Sinkiewicz G, Jakobsson T, Fredrikson M, Björkstén B.  Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life. J Pediatr Gastroenterol Nutr.2009 Sep;49(3):349-354. [PubMed] [CrossRef]
23. Sepp E, Julge K, Vasar M, Naaber P, Björksten B, Mikelsaar M. Intestinal microflora of Estonian and Swedish infants. Acta Paediatr. 1997 Sep;86(9):956-961. [PubMed] [CrossRef]
24. Matsuki S, Ozaki E, Shozu M,  Inoue M, Shimizu S, Yamaguchi N, et al. Colonization by Clostridium difficile of neonates in a hospital, and infants and children in three day-care facilities of Kanazawa, Japan. Int Microbiol. 2005 Mar;8(1):43-48. [PubMed]
25. Cimperman L, Bayless G, Best K, Diligente A, Mordarski B, Oster M, et al. A randomized, double-blind, placebo-controlled pilot study of Lactobacillus reuteri ATCC 55730 for the prevention of antibiotic-associated diarrhea in hospitalized adults. J Clin Gastroenterol. 2011 Oct;45(9):785-789. [PubMed] [CrossRef]
26. Agustina R, Kok FJ, van de Rest O, Fahmida U, Firmansyah A, Lukito W, et al. Randomized trial of probiotics and calcium on diarrhea and respiratory tract infections in Indonesian children. Pediatrics. 2012 May;129(5):1155-1164. [PubMed] [CrossRef].

Received: 22 July 2015
Published online: 07 October 2015

back to Online Journal