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Koh, Seo, and Lee: A Retrospective Analysis of Characteristics of Probiotics Associated with Invasive Bacterial Infections in Children
Original Article

Pediatric Infection & Vaccine 2017; 24(3): 168-177.

Published online: 21 December 2017

DOI: https://doi.org/10.14776/piv.2017.24.3.168

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

June Young Koh, Euri Seo, Jina Lee

Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, the Republic of Korea.

Corresponding author (entier@amc.seoul.kr)

Received 16 August 2017       Revised 2 October 2017       Accepted 13 October 2017

Copyright © 2017 The Korean Society of Pediatric Infectious Diseases

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.

Keywords: Probiotics, Lactobacillus, Saccharomyces, Safety, Korea

Figures and Tables

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.

piv-24-168-g001
Table 1

Demographics Characteristics of Patients with Invasive Infection caused by Lactobacillus spp. and Saccharomyces spp.

piv-24-168-i001

Values are presented as median (range) or number (%).

*Preterm is defined as babies born alive before 37 weeks of pregnancy are completed.

†Congenital heart diseases include functional single ventricle (n=2), double outlet ventricle with subaortic ventricular septal defect (n=1), complete atrioventricular septal defect (n=1), pulmonary atresia with ventricular septal defect (n=1), and tetralogy of Fallot (n=1).

‡Malignancy includes acute lymphoblastic leukemia (n=1), anaplastic large cell lymphoma (n=1), haemophagocytic lymphohistiocytosis (n=1), langerhans cell histiocytosis (n=1), and dysembryoblastic neuroepithelioma (n=1).

∫Neuromuscular disease includes Krabbe's disease (n=1), seizure disorder (n=1), and status epilepticus (n=1).

∥Chronic GI disorder includes necrotizing enterocolitis (n=1), autoimmune enteropathy (n=1), and meconium plug syndrome (n=1).

Chronic lung disease includes cystic fibrosis (n=1) and cytomegalovirus pneumonitis (n=1).

**Others includes brachial cleft cyst (n=3).

Abbreviations: GI, gastrointestinal; ICU, intensive care unit; ANC, absolute neutrophil count.

Table 2

Clinical Manifestations and Outcomes of Invasive Infection caused by Lactobacillus spp. and Saccharomyces spp.

piv-24-168-i002

Values are presented as number (%) or median (range).

*Polymicrobial infection includes coinfection and superinfection.

†Coinfection includes 3 cases of bacteremia caused by Bacteroides caccae, Staphylococcus aureus, Neisseria sicca, respectively.

‡Superinfection includes 1 cases of fungemia caused by Candida glabrata .

∫CLABSI is defined10) as a laboratory-confirmed bloodstream infection where central line or umbilical catheter was in place for >2 calendar days on the date of event, with day of device placement being day 1, and the line was also in place on the date of event or the day before.

∥Deep seated infection includes infected bronchial cleft cyst (n=2), and wound infection (n=1).

An episode resulting in intensive care unit stay, mechanical ventilation, vasopressors, and inotropics and/or death was considered to be severe disease.

Abbreviations: CLABSI, central line-associated blood stream infection; ICU, intensive care unit.

Table 3

Description of Five Fatal Cases*

piv-24-168-i003

*There was no evidence of polymicrobial infection including superinfection and coinfection.

†Risk factor includes ICU stay before infection, presence of CL, and IC.

Abbreviations: ICU, intensive care unit; CL, central line; IC, immunocompromised state; FSV, functional single ventricle; L, Lactobacillus, spp.; MEM, meropenem; VAN, vancomycin; HLH, haemophagocytic lymphohistiocytosis; S, Saccharomyces cerevisiae; TZP, piperacillin-tazobactam; LAB, liposomal amphotericin B; LCH, langerhans cell histiocytosis; AMK, amikacin; CLR, clarithromycin; CST, colistin; AMB, amphotericin B deoxycholate; DORV, double outlet ventricle; IPM, imipenem; TOF, tetralogy of Fallot.

Table 4

Comparison of Demographic and Predisposing Factors for Clinically Severe Infections*

piv-24-168-i004

Values are presented as median (range) or number (%).

*An episode resulting in intensive care unit stay, mechanical ventilation and/or death was considered to be severe disease.

†Logistic regression analysis was carried out including the factors that were significantly different depending on clinical severity.

‡With a reference of Lactobacillus.

Abbreviations: OR, odds ratio; CI, confidence interval; NA, not applicable; GI, gastrointestinal; ICU, intensive care unit; ANC, absolute neutrophil count.

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