Editorial Commentary: Clostridium difficile in Children: Colonization and Consequences

Abstract

The incidence of Clostridium difficile infection (CDI) has dramatically increased in the past decade. In some parts of the United States, CDI now surpasses methicillin-resistant Staphylococcus aureus as the most common healthcare-associated infection [1]. CDI also appears to be causing increasingly severe illnesses and more deaths, and exerting a growing burden on healthcare systems [2–6]. The preponderance of literature on this problem has been derived from adult clinical and epidemiologic studies. Clostridium difficile was first described in the stools of neonates in 1935, and termed Bacillus difficilis “because of the unusual difficulty . . . encountered in its isolation and study” [7]. Although Hall and O’toole found that strains from infant stools were virulent when inoculated into guinea pigs and rabbits [7], C. difficile was not generally considered to be a human pathogen until 4 decades later, when Bartlett et al linked these bacteria to antibioticassociated pseudomembranous colitis [8]. Now, nearly 4 more decades after that seminal association, emerging data suggest we need to focus on the biology of C. difficile in children. Sammons et al [9], in the current issue of Clinical Infectious Diseases, highlight the importance of C. difficile as a pediatric pathogen. They report a large multicenter retrospective analysis of morbidity and mortality associated with CDI in children. Children who develop symptomatic C. difficile diarrhea after admission to the hospital have a 6-fold greater risk of dying during that hospitalization than do controls with similar underlying disease and risk factors. In addition, children with CDI have significantly longer hospital stays and incur more costs than matched controls. These results are generalizable to the greater US population because the large dataset was obtained from children’s hospitals around the country. The study by Sammons et al [9] has additional strengths: They performed rigorous propensity score matching that took into consideration not only demographic data but also risk factors that would impact disease severity. The authors therefore minimized the bias that is inherent to studies of C. difficile in pediatrics, because children with significant comorbidities are at higher risk of acquiring C. difficile, and it might be difficult to attribute causality to C. difficile in these settings. They complemented this thorough evaluation with a sensitivity analysis that fortified their results. Their study had several limitations (as they acknowledge), such as using the third day of hospitalization as a cutoff to distinguish community-onset from hospital-onset disease, and the potential inaccuracy of information obtained from an administrative dataset. Taken together, the data reported by Sammons et al compel us to end our complacency about childhood CDI. It is understandable why we have discounted the importance of CDI in childhood. Multiple studies demonstrate that healthy infants often excreteC. difficile [10– 24], so attribution of pathogenicity in childhood cannot be claimed with conviction when a child with diarrhea has a positive C. difficile assay. Indeed, in a recent Seattle study, the frequency of C. difficile carriage was higher in controls than cases in children younger than 2 years [25]. Nonetheless, multiple reports over the past decade serve as preludes for the article by Sammons et al: Hospital diagnoses of pediatric C. difficile infection are increasing [26–30], and C. difficile infections are very common in children with inflammatory bowel diseases [31] and cancer [32]. Nylund et al [30] refuted the contention that C. difficile infections in Received 1 March 2013; accepted 4 March 2013; electronically published 26 March 2013. Correspondence: Phillip I. Tarr, MD, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8208, St Louis, MO 63110 (tarr@kids.wustl.edu). Clinical Infectious Diseases 2013;57(1):9–12 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/cid/cit160