Clostridium difficile Infection in Children: A Community-based Epidemiological Study

Abstract

Purpose: Numerous recent reports have shown increasing incidence and severity of Clostridium difficile infection (CDI), as well as decreased response to metronidazole, in adults. Little is known about the epidemiology or response to treatment of CDI in children. Methods: A computerized diagnostic index, which captures all inpatient and outpatient medical encounters for Olmsted County, MN residents, was used to identify children with CDI. All cases <18 years of age who were county residents from 1991-2005 were reviewed to confirm the diagnosis, document demographic data, and assess risk factors and treatment outcomes. Definite CDI was defined as a positive C. difficile stool assay or pseudomembranous colitis on endoscopy or histology. Severe disease was defined by a WBC > 15,000, creatinine rise of > 50% from baseline, ICU admission, need for surgery, or death. Hospital acquired CDI was defined as onset of symptoms >=48 hours after hospitalization, or within 4 weeks from hospital discharge. Results: 8% of all cases (30/385) occurred in children. 60% of pediatric cases occurred after 2001. Median age at symptom onset was 19 months (range: 1 month to 17 years), and 43% were female. 73% of cases occurred in children < 3 years of age. 27% had hospital-acquired infection and 83% had community acquired infection, of which 4 ended up being hospitalized for CDI. 25 of 30 (83%) had been treated with an antibiotic within 90 days of CDI diagnosis. 8/30 (27%) had a recent hospitalization. 17% children had neither recent hospitalization nor antibiotic exposure. Metronidazole was the initial treatment in 22/30 cases (71%) and oral vancomycin in 5 cases (16%). There was no documented treatment in the other 3 cases. 22% of the children treated with metronidazole had one or more recurrence, and 20% treated with vancomycin had a recurrence. There were no documented changes in the initial treatment course due to non-response. There were 4 severe cases, all defined by leukocyte count > 15,000. Of these severe cases, 2 were already in the hospital and 1 was hospitalized for CDI. All severe cases responded to initial therapy with no complications. One severe case had 2 recurrences. Conclusion: In this population-based cohort, CDI was uncommon in children from 1991-2005, although there was a significant increase in cases after 2001. A substantial fraction of cases were community acquired, and would be missed if hospital information was the primary source of data. Severe infection was uncommon, responded to standard therapy and lead to no complications. Metronidazole was the most common treatment, and there were no differences in response or recurrence rates between metronidazole and vancomycin. This research was supported by an industry grant from ViroPharma.