Clostridium difficile Infections in Children

Abstract

Clostridium difficile, a spore-forming Grampositive bacillus, is a frequent cause of antibiotic-associated diarrhea and a common nosocomial pathogen. Clinical manifestations of disease range from self-limited diarrhea to life-threatening colitis and death. Historically, C. difficile-associated infection (CDI) has been much less common in children than adults. Up to 70% of infants may be asymptomatically colonized with C. difficile, including toxigenic strains. Rates of colonization decrease with age, falling in the second year of age to 6%. Rates of colonization in children over age 2 are similar to those in adults ( 3%). Infants may acquire colonization early in the first week of life. Studies examining risk factors for C. difficile colonization have failed to show a consistent association between mode of delivery or receipt of formula versus breast milk. However, healthcareassociated acquisition of the organism is well described in neonatal intensive care units (NICUs), and C. difficile contamination of the NICU environment has been demonstrated. Most studies have failed to show an epidemiologic association between colonization and disease in infants 1 year of age. For example, in one Swedish study, C. difficile was isolated with equal frequency in healthy children between 1 week and 1 year of age (17%) and children 6 years of age with diarrhea (18%). In a study of outpatient children, C. difficile was isolated from 7% of patients with diarrhea and 14.8% of healthy controls. Children with C. difficile were younger than children without the organism (P 0.05); prior antibiotic exposure was noted in only 22%. In another study, toxin B was identified in 4.2% of 618 children with diarrhea and in an equivalent proportion of healthy controls. In contrast, Tullus et al observed all-cause diarrhea to be more frequent in children colonized with C. difficile after the age of 6 months. Similar findings have been noted in most controlled studies of NICU patients. C. difficile toxin was recovered from the stools of 55% of patients in one NICU but signs of enteric disease, including necrotizing enterocolitis, occurred with equal frequency in both toxin-positive and toxin-negative infants. Data from juvenile rabbits suggest that the lack of disease in colonized human infants may be related to the relative absence of receptors for toxin A on immature enterocytes. However, more recent data suggest the numbers of toxin A receptors present on the enterocytes of neonatal pigs are adequate to cause disease, suggesting that differences in the appearance of receptors with age may be a species-specific phenomenon. Sporadic case reports suggest that severe CDI occasionally occurs in infants, especially those with underlying intestinal pathology. For example, C. difficile pseudomembranous colitis has been identified at autopsy in infants with Hirshprung’s disease. Fatal C. difficile-associated pseudomembranous colitis has also been described in a premature infant with necrotizing enterocolitis. The accurate diagnosis of CDI in young children may be complicated by a lack of specificity of commonly used enzyme immunoassays in very young children. Most of these tests have not been validated for use in young children. Young children with asymptomatic C. difficile colonization nevertheless may represent a reservoir for transmission of disease to others. A 19-year-old woman developed CDI in the immediate postpartum period. Although her symptoms resolved with metronidazole treatment, she developed 3 recurrences. Her asymptomatic infant was a carrier of the identical strain of C. difficile, suggesting the infant was a potential source of the mother’s recurrent disease. The emergence of an epidemic strain of binary toxin-producing-C. difficile, B1/ NAP1/027, may be changing the epidemiology of CDI in children. B1/NAP1/027 has been associated with severe disease in both adult and pediatric patients without recent exposure to healthcare facilities and, in some cases, without recent antimicrobial use. In 2005, the Centers for Disease Control and Prevention reported cases of severe CDI in populations previously at low risk for disease, including healthy children with no recent antibiotic use. A 5-year retrospective study performed at a tertiary care children’s hospital revealed an increase in the number of patients seen in the emergency department with community-acquired CDI; 43% lacked From the *Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY; and ††Centers for Disease Control and Prevention, Atlanta, GA. Disclaimer: The findings and conclusions in this presentation are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. Copyright © 2009 by Lippincott Williams & Wilkins ISSN: 0891-3668/09/2802-0145 DOI: 10.1097/INF.0b013e318198c984 CONTENTS C. difficile in Children Tuberculous Meningitis and HIV EDITORIAL BOARD Co-Editors: Margaret C. Fisher, MD and Gary D. Overturf, MD Editors for this Issue: Charles R. Woods, MD, and Michael Cappello, MD Board Members Michael Cappello, MD Ellen G. Chadwick, MD Janet A. Englund, MD Leonard R. Krilov, MD Charles T. Leach, MD Kathleen McGann, MD Jennifer S. Read, MD Jeffrey R. Starke, MD Geoffrey A. Weinberg, MD Leonard Weiner, MD Charles R. Woods, MD