Pediatr Infect Vaccine.  2017 Dec;24(3):168-177. 10.14776/piv.2017.24.3.168.

A Retrospective Analysis of Characteristics of Probiotics Associated with Invasive Bacterial Infections in Children

• Koh JY
• Seo E
• Lee J

• KMID: 2401392
• DOI: http://doi.org/10.14776/piv.2017.24.3.168

Abstract

PURPOSE
The purpose of this study was to analyze the clinical features and risk factors of invasive infections caused by Lactobacillus spp. and Saccharomyces spp., components of commercially available probiotics.
METHODS
We analyzed demographic and clinical data from children ≤18 years of age with an invasive infection caused by Lactobacillus spp. or Saccharomyces spp. at the Asan Medical Center Children's Hospital from January 1998 to June 2016. Probiotic consumption data were also analyzed.
RESULTS
During the study period, a total of 24 episodes of invasive infections were caused by Lactobacillus spp. (n=16) and Saccharomyces cerevisiae (n=8). Along with the increase of probiotic use (755,594 [days/1,000 patient-admission days] in 2001 to 2005, 1,444,066 in 2006 to 2010, and 6,904,736 in 2011 to 2016), the incidence of probiotic-associated invasive infection increased (R2=0.70). The median age of the patients was 1.8 years (range, 2 months to 17 years), and most of them had underlying medical conditions. The 30-day mortality rate was 20.8% (5/24), and 11 (45.8%) of these patients resulted from a severe invasive infection. We determined the risk factors for invasive infection to be: previous intensive care unit stay (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.5 to 6.1] and the presence of a central venous catheter (OR, 2.2; 95% CI, 1.2 to 4.3).
CONCLUSIONS
Although the probiotic-associated invasive infections rarely occurred in children, the incidence has increased along with probiotic pressure. Judicious use of probiotics is mandatory, especially in young children with underlying medical conditions and continuous surveillance will be needed to minimize the safety concerns.

Keyword

Probiotics; Lactobacillus; Saccharomyces; Safety; Korea

MeSH Terms

Bacterial Infections*
Central Venous Catheters
Child*
Chungcheongnam-do
Humans
Incidence
Intensive Care Units
Korea
Lactobacillus
Mortality
Probiotics*
Retrospective Studies*
Risk Factors
Saccharomyces
Saccharomyces cerevisiae

Figure

• 

  Figure 1 Trend of probiotics usage and incidence of invasive infection of Lactobacillus spp. and Saccharomyces cerevisiae. (A) For 19 years from 1998 to 2016, 24 cases of invasive infection of Lactobacillus spp. and S. cerevisiae has occurred. (B) During recent 15 years, the incidence of invasive infection of Lactobacillus spp. and S. cerevisiae has increased significantly with increasing use of probiotics (R2=0.53 [Lactobacillus spp.], R2=0.39 [S. cerevisiae], R2=0.70 [total]; each P for trend <0.05). *Incidence of invasive infection is expressed as number of cases per year. †Probiotic consumption is expressed as days on the probiotics per 1,000 patient admission days per year.

Reference

1. Araya M, Morelli L, Reid G, Sanders ME, Stanton C. Guidelines for the evaluation of probiotics in food: report of a joint FAO/WHO working group on drafting guidelines for the evaluation of probiotics in food 2002 [Internet]. Geneva: World Health Orgarnization;2017. cited 2017 Nov 18. Available from: http://www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf.

2. Lherm T, Monet C, Nougiere B, Soulier M, Larbi D, Le Gall C, et al. Seven cases of fungemia with Saccharomyces boulardii in critically ill patients. Intensive Care Med. 2002; 28:797–801.

3. Cassone M, Serra P, Mondello F, Girolamo A, Scafetti S, Pistella E, et al. Outbreak of Saccharomyces cerevisiae subtype boulardii fungemia in patients neighboring those treated with a probiotic preparation of the organism. J Clin Microbiol. 2003; 41:5340–5343.

4. Mackay AD, Taylor MB, Kibbler CC, Hamilton-Miller JM. Lactobacillus endocarditis caused by a probiotic organism. Clin Microbiol Infect. 1999; 5:290–292.

5. Rautio M, Jousimies-Somer H, Kauma H, Pietarinen I, Saxelin M, Tynkkynen S, et al. Liver abscess due to a Lactobacillus rhamnosus strain indistinguishable from L. rhamnosus strain GG. Clin Infect Dis. 1999; 28:1159–1160.

6. Hempel S, Newberry S, Ruelaz A, Wang Z, Miles JN, Suttorp MJ, et al. Safety of probiotics used to reduce risk and prevent or treat disease. Evid Rep Technol Assess (Full Rep). 2011; (200):1–645.

7. Wallace TC, MacKay D. The safety of probiotics: considerations following the 2011 U.S. Agency for Health Research and Quality report. J Nutr. 2011; 141:1923–1924.

8. Mitterdorfer G, Mayer HK, Kneifel W, Viernstein H. Protein fingerprinting of Saccharomyces isolates with therapeutic relevance using one- and two-dimensional electrophoresis. Proteomics. 2002; 2:1532–1538.

9. van der Aa Kuhle A, Jespersen L. The taxonomic position of Saccharomyces boulardii as evaluated by sequence analysis of the D1/D2 domain of 26S rDNA, the ITS1-5.8S rDNA-ITS2 region and the mitochondrial cytochromecoxidase II gene. Syst Appl Microbiol. 2003; 26:564–571.

10. Center for Disease Control and Prevention/National Healthcare Safety Network. Bloodstream infection event (central line-associated bloodstream infection and noncentral line-associated bloodstream infection) [Internet]. Atlanta: Center for Disease Control and Prevention;2016. cited 2017 Nov 17. Available from: http://www.cdc.gov.

11. Salminen MK, Tynkkynen S, Rautelin H, Saxelin M, Vaara M, Ruutu P, et al. Lactobacillus bacteremia during a rapid increase in probiotic use of Lactobacillus rhamnosus GG in Finland. Clin Infect Dis. 2002; 35:1155–1160.

12. Salminen MK, Rautelin H, Tynkkynen S, Poussa T, Saxelin M, Valtonen V, et al. Lactobacillus bacteremia, clinical significance, and patient outcome, with special focus on probiotic L. rhamnosus GG. Clin Infect Dis. 2004; 38:62–69.

13. Munoz P, Bouza E, Cuenca-Estrella M, Eiros JM, Perez MJ, Sanchez-Somolinos M, et al. Saccharomyces cerevisiae fungemia: an emerging infectious disease. Clin Infect Dis. 2005; 40:1625–1634.

14. Enache-Angoulvant A, Hennequin C. Invasive Saccharomyces infection: a comprehensive review. Clin Infect Dis. 2005; 41:1559–1568.

15. U.S. Department of Health and Human Services, Food and Drug Administration. Investigational new drug applications (INDs): determining whether human research studies can be conducted without an IND, guidance for clinical investigators [Internet]. Silver Spring: FDA;2013. cited 2017 Nov 17. Available from: https://www.fda.gov/downloads/drugs/guidances/ucm229175.pdf.

16. Boyle RJ, Robins-Browne RM, Tang ML. Probiotic use in clinical practice: what are the risks. Am J Clin Nutr. 2006; 83:1256–1264.

17. Hennequin C, Kauffmann-Lacroix C, Jobert A, Viard JP, Ricour C, Jacquemin JL, et al. Possible role of catheters in Saccharomyces boulardii fungemia. Eur J Clin Microbiol Infect Dis. 2000; 19:16–20.

18. Atici S, Soysal A, Karadeniz Cerit K, Yilmaz S, Aksu B, Kiyan G, et al. Catheter-related Saccharomyces cerevisiae fungemia following Saccharomyces boulardii probiotic treatment: in a child in intensive care unit and review of the literature. Med Mycol Case Rep. 2017; 15:33–35.

19. Oggioni MR, Pozzi G, Valensin PE, Galieni P, Bigazzi C. Recurrent septicemia in an immunocompromised patient due to probiotic strains of Bacillus subtilis. J Clin Microbiol. 1998; 36:325–326.

20. Bassetti S, Frei R, Zimmerli W. Fungemia with Saccharomyces cerevisiae after treatment with Saccharomyces boulardii. Am J Med. 1998; 105:71–72.