We found that CDI-related hospitalizations as a proportion of all hospitalizations among US children increased dramatically between 1997 and 2006, from 7.24 to 12.80/10,000 hospitalizations. Most of this increase occurred between 2000 and 2006, which possibly reflects spread of the new C
strain into medical institutions. Consistent with finding from previous studies, children 1–4 years of age were as a group most likely to have a hospitalization that was CDI related, and newborns were the least likely. Such a low rate in newborns is consistent with long-standing recommendations against routine testing of children <1 year of age (21
). This rate, rather than representing a truly low risk for CDI in this age group, may be the result of an inflated denominator, given that most births in the United States occur in a hospital setting. In contrast, non-newborn infants (i.e., those <1 year of age and not meeting the newborn definition) had the second highest rate of CDI-related hospitalizations. In addition to the overall increase in pediatric CDI-related hospitalizations, there was a coincident increase in hospitalizations either resulting from or complicated by rotavirus infection.
Several of these findings are consistent with other recent epidemiologic and microbiology-based investigations. For example, Klein et al. examined billing records for the testing of diarrheal stool specimens from children who came to the emergency department at a children’s hospital between 1998 and 2001 and identified C
toxin in 6.7% (8
). However, viral pathogens were isolated from 33% of the samples. A more recent study tracked changes between 2001 and 2006 in the epidemiology of C
toxin testing performed on children at 1 academic medical center (11
). The proportion of children <2 years of age who were positive increased from 46% to 64%, and there was a substantial increase in the incidence of community-onset infections and a concomitant decrease in hospital-onset infections. Interestingly, 43% of all patients had no recent history of exposure to antimicrobial drugs (11
). Kim et al. estimated the rate of CDI in 22 US children’s hospitals and also found a steady increase from 4.4 cases/10,000 patient-days in 2001 to 6.5 cases/10,000 patient-days in 2006 (9
The role of C
in the pathogenesis of disease among non-newborn children <1 year of age remains perplexing. Because of historically low rates of pseudomembranous colitis (the characteristic pathologic lesion caused by toxins A and B) among infants and high rates of asymptomatic C
carriage in neonates, it has been recommended that laboratory testing for CDI not be routinely performed for children <1 year of age (21
). However, in the study by Kim et al., in which tests for C
laboratory assays were combined with ICD-9-CM discharge diagnoses, 26% of all CDI cases were identified in infants and 5% in neonates (9
). Although rates increased from 2001 through 2006 for children 1–5 years of age (from 0.7 to 1.3 cases/1,000 hospitalizations; p = 0.04) and those 5–17 years of age (from 1.2 to 1.8/1,000 hospitalizations; p = 0.03), these rates did not change for the group <1 year of age (from 3.1 to 3.0/1,000 hospitalizations).
Our data, which are more broadly representative of all pediatric admissions in the United States, have similar trends between 2000 and 2006 for children 1–4 years of age (from 2.68 to 4.52/1,000 hospitalizations) and those 5–17 years of age (from 1.62 to 2.86/1,000 hospitalizations). In contrast, the <1 year age group rates in our time series were an order of magnitude lower in 2000 and 2006. However, the rate for non-newborn children <1 year of age in our 2006 cross-sectional study (3.20/1,000 hospitalizations) was comparable with that observed by Kim et al. (9
). The lower overall rate for children <1 year of age from our data likely reflects that healthy newborns have an exceedingly low risk for CDI and that although it is unlikely for these children to end up at a children’s hospital unless peripartum problems are encountered, neonates account for >80% of all hospitalized children <1 year of age in the HCUP and KID databases.
We could not determine whether the relatively high rate of CDI-related hospitalizations among non-newborn infants represents predominantly true disease or colonization. Although more specific than recovery of a toxin-producing strain from culture, even the detection of free toxins A, B, or both in the stool of a symptomatic infant does not ensure a pathogenic role for C
, especially if another cause for diarrhea can be identified. Rates of hospitalizations for rotavirus infections have exhibited a similar increase as those with CDI between 1997 and 2006. Although 2 recent analyses of discharge data for adults suggest that non-CDI causes of diarrhea are not likely leading to a reporting bias as the explanation for the observed increase in CDI rates (22
), the situation may be different for children in whom rotavirus is a serious pathogen and related hospitalizations are clearly increasing. Although Kim et al. did not report an increase in the frequency of testing for C
in their study, our findings implicate this finding as a distinct possibility that needs to be investigated further (9
Our study has several limitations. First, case identification was based on administrative coding, thus predisposing to misclassification. However, the degree of misclassification may not be substantial because multiple studies have shown the ICD-9-CM code 008.45 to be a relatively accurate way to identify CDI (24
). Second, because we had no clinical data available, we could not distinguish stool colonization from CDI infection. Third, we were unable to distinguish community-acquired from healthcare-associated disease.
However, our study has several strengths. Because we explored 2 databases and discovered results that are highly consistent not only with each other but with those of previous recent investigations, we have augmented the accuracy of estimates of pediatric CDI incidence (9
). In addition, our data are generalizable to most US-based institutions that care for the pediatric populations. This generalizability sets our results apart from those reported previously because they were limited to the highly specialized setting of children’s hospitals (8
In summary, the incidence of CDI in the pediatric population appears to be increasing in US hospitals. A reporting bias for diarrheal diseases may play a role in this trend given the concomitant increase in rotavirus-related hospitalizations we identified. Future data may clarify this finding because widespread immunization with available rotavirus vaccines may soon lead to reduced incidence of related hospitalizations. The low incidence of CDI-related hospitalizations among newborns reflects current recommendations against routine testing and may support the concept that C. difficile does not cause disease among neonates. In contrast, the relatively high rate of CDI-related hospitalizations among non-newborn infants indicates an urgent need for studies to determine how often C. difficile causes true disease in this population.