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소아청소년에서 발생한 유산균 제제에 포함된 균주에 의한 침습성 감염증의 후향적 분석

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

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목적: 국내 소아에서 발생한 유산균 제제 내 포함 균주(Lactobacillus spp. 및 Saccharomyces spp.)에의한 침습적 감염증의 임상 경과를 기술하고 중증 감염증 발생과 관련된 인자들을 분석하였다. 방법: 1998년 1월부터 2016년 6월까지 서울아산병원 어린이병원에서 18세 이하의 소아청소년 환아에게서 발생한 Lactobacillus spp. 및 Saccharomyces spp.에 의한 침습적 감염증의 의무기록과 2001년1월부터 2016년 6월까지 원내에서 처방된 유산균 제제 처방량 자료를 후향적으로 분석하였다. 결과: 연구 기간 동안 총 24명의 침습적 감염이 발생하였다(Lactobacillus spp. 16예 및 Saccharomyces spp. 8예). 유산균 제제의 처방량은 2001년부터 2016년까지 통계적으로 유의미하게 증가하는 양상을보였으며, 이에 따라 침습적 감염증의 발생률도 증가하였다(R 2 =0.70). 환아들의 중간 연령은 1.8세(범위, 2개월–17세)이었고, 1명을 제외한 환아에서 기저질환을 동반하였다. 30일 사망률은 20.8% (5/ 24)였으며, 중증 감염증은 11예(45.8%)에서 발생하였다. 어린 연령의 환아이거나(P =0.02), 선천 심질환이 있는 경우(P =0.01) 또는 침습적 감염증 발생 전 중환자실 재실 중이었거나(odds ratio [OR], 3.0; 95% confidence interval [CI], 1.5–6.1), 중심정맥관을 가지고 있던 경우(OR, 2.2; 95% CI, 1.2–4.3)에 통계적으로 유의미하게 중증 감염으로의 발현이 증가하였다. 결론: 소아에서의 유산균 제제 내 균주에 의한 감염증은 흔하게 발생하지는 않지만, 유산균 제제의 사용량 증가와 함께 증가하는 양상을 보였다. 어린 환아 및 기저질환을 가지고 있거나 중환자실 치료 또는 중심정맥관을 보유하고 있는 환아에 대해서는 안전성을 고려하여 유산균 제제의 사용에 주의를 기울여야 한다.

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.

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