Clinical Efficacy and Microbiome Changes Following Fecal Microbiota Transplantation in Children With Recurrent Clostridium Difficile Infection

Xiaolu Li,Dongbao Yu,Dan Li,Xuefeng Gao,Hui Hu,Yongmei Xiao,Ting Zhang,Yizhong Wang,Guangjun Yu

doi:10.3389/fmicb.2018.02622

Abstract

Fecal microbiota transplantation (FMT) has been shown as an effective treatment for recurrent clostridium difficile infection (RCDI) in adults. In this study, we aim to evaluate the clinical efficacy of FMT in treating children with RCDI, and explore fecal microbiota changes during FMT treatment. A total of 11 RCDI subjects with a median age of 3.5 years were enrolled in this single-center prospective pilot study. All patients were cured (11/11, 100%) by FMT either through upper gastrointestinal tract route with a nasointestinal tube (13/16, 81.2%) or lower gastrointestinal tract route with a rectal tube (3/16, 18.8%). The cure rate of single FMT was 63.6% (7/11), and 4 (4/11, 36.4%) cases were performed with 2 or 3 times of FMT. Mild adverse events were reported in 4 children (4/11, 36.4%), including transient diarrhea, mild abdominal pain, transient fever and vomit. Gut microbiota composition analysis of 59 fecal samples collected from 34 participants (9 RCDI children, 9 donors and 16 health controls) showed that the alpha diversity was lower in pediatric RCDI patients before FMT than the healthy controls and donors, and fecal microbial community of pre-FMT samples (beta diversity) was apart from that of healthy controls and donors. No significant differences in alpha diversity, beta diversity or phylogenetic distance were detected between donors and healthy controls. Both the richness and diversity of gut microbiota were improved in the pediatric RCDI patients after FMT, and the bacteria community was shifted closer to the donor and healthy control group. Furthermore, FMT re-directed gut microbiome functions of pediatric RCDI toward a health state. Our results indicate that it is safe and tolerant to use FMT in treating pediatric RCDI. FMT shifted the gut microbiome composition and function in children with RCDI toward a healthy state.

Highlights

Clostridium difficile (CD) is a leading causative pathogen of antibiotic-associated and healthcare-associated infective diarrhea
Conventional antibiotic treatment is less ineffective for refractory, recurrent and complicated CD infection (CDI), and new therapeutic approaches are needed for managing recurrent clostridium difficile infection (RCDI)
All subjects were treated with 1–2 episodes of oral antibiotics before Fecal microbiota transplantation (FMT), 7 patients (7/11, 63.6%) were given oral vancomycin, and all 11 (11/11, 100%) subjects received metronidazole treatment

Summary

Introduction

Clostridium difficile (CD) is a leading causative pathogen of antibiotic-associated and healthcare-associated infective diarrhea. Vancomycin or fidaxomicin is successful in most of CDI subjects, recurrence after completion of a first treatment course ranges from 15 to 20%, and increases up to 45–60% after the first recurrence (McFarland et al, 2002; Kelly and LaMont, 2008; Brandt, 2013). Studies revealed that the recurrence rate of pediatric RCDI after first-line treatment varied from 2.6 to 30% in different examined population, with the frequency of recurrence rising further after subsequent infections (Barbut et al, 2000; McFarland et al, 2002; Pai et al, 2012; Khanna et al, 2013; Nicholson et al, 2015). Conventional antibiotic treatment is less ineffective for refractory, recurrent and complicated CDI, and new therapeutic approaches are needed for managing RCDI

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