Background:The incidence and severity of Clostridium difficile infection (CDI) is increasing among adults; however, little is known about the epidemiology of CDI among children. Methods: We conducted a nested case-control study to identify the risk factors for and a prospective cohort study to determine the outcomes associated with severe CDI at 2 children's hospitals. Severe CDI was defined as CDI and at least 1 complication or Ն2 laboratory or clinical indicators consistent with severe disease. Studied outcomes included relapse, treatment failure, and CDI-related complications. Isolates were tested to determine North American pulsed-field gel electrophoresis type 1 lineage. Results: We analyzed 82 patients with CDI, of whom 48 had severe disease. Median age in years was 5.93 (1.78 -12.16) and 1.83 (0.67-8.1) in subjects with severe and nonsevere CDI, respectively (P ϭ 0.012). All patients with malignancy and CDI had severe disease. Nine subjects (11%) had North American pulsed-field gel electrophoresis type 1 isolates. Risk factors for severe disease included age (adjusted odds ratio ͓95% confidence interval͔: 1.12 ͓1.02, 1.24͔) and receipt of 3 antibiotic classes in the 30 days before infection (3.95 ͓1.19, 13.11͔). If infants less than 1 year of age were excluded, only receipt of 3 antibiotic classes remained significantly associated with severe disease. Neither the rate of relapse nor treatment failure differed significantly between patients with severe and nonsevere CDI. There was 1 death. Conclusions: Increasing age and exposure to multiple antibiotic classes were risk factors for severe CDI. Although most patients studied had severe disease, complications were infrequent. Relapse rates were similar to those reported in adults.

These results demonstrate that the use of administrative data for CDI is a reliable and accurate method for identifying pediatric patients with CDI. The use of administrative data could facilitate the completion of larger studies due to its greater accessibility and reduced costs.

Levels of PAI-1 and sCD40L did not significantly increase after smallpox vaccination. Vaccine-induced alterations in levels of these prothrombotic proteins do not appear to play a role in ischemic events observed after smallpox vaccination.