The role of Clostridium difficile in the paediatric and neonatal gut — a narrative review

Abstract

Clostridium difficile is an important nosocomial pathogen in adults. Its significance in children is less well defined, but cases of C. difficile infection (CDI) appear to be increasingly prevalent in paediatric patients. This review aims to summarize reported Clostridium difficile carriage rates across children of different age groups, appraise the relationship between CDI and factors such as method of delivery, type of infant feed, antibiotic use, and co-morbidities, and review factors affecting the gut microbiome in children and the host immune response to C. difficile. Searches of PubMed and Google Scholar using the terms ‘Clostridium difficile neonates’ and ‘Clostridium difficile children’ were completed, and reference lists of retrieved publications screened for further papers. In total, 88 papers containing relevant data were included. There was large inter-study variation in reported C. difficile carriage rates. There was an association between CDI and recent antibiotic use, and co-morbidities such as immunosuppression and inflammatory bowel disease. C. difficile was also found in stools of children with diarrhoea attributed to other pathogens (e.g. rotavirus). The role of C. difficile in the paediatric gut remains unclear; is it an innocent bystander in diarrhoeal disease caused by other organisms, or a pathogen causing subclinical to severe symptoms? Further investigation of the development of serological and local host response to C. difficile carriage may shed new light on disease mechanisms. Work is underway on defining a framework for diagnosis and management of paediatric CDI.Electronic supplementary materialThe online version of this article (doi:10.1007/s10096-016-2639-3) contains supplementary material, which is available to authorized users.

Impact and Time Course of <b><i>Clostridium difficile</i></b> Colonization in Very Low Birth Weight Infants

“…However, these findings were not significant in our study. Also, similarly to other studies [6, 7, 14, 21], in-hospital C. difficile colonization was not associated with the development of NEC in our study. This is an interesting finding as a recent in vivo study in mice described that neonatal acquisition of Clostridium spp.…”

Understanding Clostridium difficile Colonization

“…A meta-analysis of studies examining pediatric C. difficile epidemiology reported an asymptomatic colonization rate of 15% for children older than 1 year of age, with the prevalence reduced to 5% in those older than 2 years of age (117). One explanation for the reduction in colonization rates after infancy is that, by 12 months, the distribution of gut flora begins to closely resemble that of a healthy adult, providing a colonization resistance effect.…”

Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

“…Asymptomatic colonization with C. difficile is common in infants; in fact, it is estimated that up to 21 to 48% of infants are asymptomatically colonized with C. difficile (62). Although it is not known why colonized infants generally do not develop disease, it has been suggested that they could be protected by a lack of functional toxin receptors or by antibodies in breast milk (63). Asymptomatic colonization can also occur in adults (62), but old age is a risk factor for the development of symptomatic CDI (64)(65)(66).…”