Co-infection as a confounder for the role of Clostridium difficile infection in children with diarrhoea: a summary of the literature

Abstract

Although Clostridium difficile is a major cause of antibiotic-associated diarrhoea in adults, the incidence and severity of C. difficile infection (CDI) in children is unclear. One complicating factor in assessing the role of CDI in children is the possibility of co-infection with other gastrointestinal pathogens. In this review, we summarise the literature concerning C. difficile co-infections in young children, in an attempt to discuss the rate of co-infections and their potential role in the severity of CDI clinical presentation. We identified 31 studies where co-infections were analysed, comprising 1,718 patients with positive C. difficile tests. The pooled percentage of reported co-infections was 20.7% (range 0-100%). Viral co-infections were most commonly reported (46%), with bacteria and parasites accounting for 14.9% and 0.01% of cases, respectively. However, the panel of co-infections tested for varied considerably among studies and 38% of stated co-infections did not have a pathogen reported. Substantial variation in how and when tests for gastrointestinal co-infections are carried out, small sample sizes and a lack of clear CDI case definitions preclude meaningful conclusions on the true rate of co-infections in this patient population. This review suggests that co-infections may be common in children with diarrhoea who tested positive for C. difficile. Given a lack of CDI case definitions, especially in young children under the age of 5 years, a broad panel of pathogens should be tested for to exclude other microbiological causes. However, the summarised poor quality of the available literature on this subject highlights a need for further studies.

Epidemiology and Factors Related to Clinical Severity of Acute Gastroenteritis in Hospitalized Children after the Introduction of Rotavirus Vaccination

“…In a recent single center European study with a modest number of fecal samples, a prevalence of 14.4% was reported ( 10 ). The overall prevalence of toxigenic C. difficile (including both mono-infection and co-infection) was approximately 5%–20% in hospitalized children with diarrhea, no different from the prevalence in hospitalized children without diarrhea ( 34 35 36 37 ). The diversity in prevalence may be largely due to the different age distribution of included children, which could be deduced from the results of this study: there was a 17.0% prevalence of toxigenic C. difficile in children aged 6–23 months in contrast to 4.4% in those 24–59 months ( P < 0.001).…”

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

“…A 2014 Polish study reports rates of 13.5 cases of CDI per 1,000 children hospitalised with diarrhoea; however, not all children were tested for viral/alternative bacterial pathogens, and those who were co-infected with C. difficile and another pathogen were recorded as being a case of CDI [ 44 ]. Indeed, a recent literature review on co-infections in children with C. difficile notes a rate of 20.7 % (range 0–100 %) for reported co-infections (predominantly viral infections), but found it difficult to draw any meaningful conclusions, given the heterogeneity between studies as to which organisms were tested for (virus/bacteria/parasite) and the difficulty in describing what constitutes CDI in the paediatric population [ 45 ].…”

Rapid change of fecal microbiome and disappearance of Clostridium difficile in a colonized infant after transition from breast milk to cow milk

“…Rates of positive C. difficile tests were the same among children with or without diarrhea [ 52 ]. More than 20 % of children with diarrhea who tested positive for C. difficile also tested positive for other pathogens, making it difficult to determine whether C. difficile was the true cause of diarrhea or part of the commensal microbiota [ 53 ]. Even when children under 2 years of age were diagnosed with CDI, the outcomes of treated and untreated CDI were not significantly different [ 54 ].…”