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42 Risk Factors and Outcomes Associated with Severe Clostridium difficile Infection (CDI) in a Cohort of Hospitalized Pediatric Patients

Saturday, April 2, 2011: 10:30 AM
Coronado A (Hilton Anatole)
Julia Francis Shaklee, MD , The Children's Hospital of Philadelphia, Philadelphia, PA
Jason Kim, MD, MSCE , The Children's Hospital of Philadelphia, Philadelphia, PA
Sarah Smathers, MS , The Children's Hospital of Philadelphia, Philadelphia, PA
Priya Prasad, MPH , The Children's Hospital of Philadelphia, Philadelphia, PA
Joan Zoltanski, MD , Rainbow Babies and Children's Hospital, Cleveland, OH
Michelle Nerandzic, BS , Louis Stokes Cleveland VA Medical Center, Cleveland, OH
Lindsey Asti, MPH , The Children's Hospital of Philadelphia, Philadelphia, PA
Susan Coffin, MD, MPH , The Children's Hospital of Philadelphia, Philadelphia, PA
Philip Toltzis, MD , Rainbow Babies and Children's Hospital, Cleveland, OH
Theoklis Zaoutis, MD, MSCE , The Children's Hospital of Philadelphia, Philadelphia, PA
Background: The incidence and severity of CDI is increasing among children and adults. Epidemiologic studies characterizing CDI among pediatric patients are lacking.

Objective: To determine the risk factors and outcomes associated with severe CDI among hospitalized pediatric patients.

Methods: We conducted a nested case control study to determine the risk factors and a prospective cohort study to determine the outcomes associated with severe CDI at 2 children’s hospitals from March 1, 2008 through December 31, 2009. Subjects with severe CDI were identified as patients with documented CDI and at least 1 known complication of CDI, e.g. pseudomembranous colitis or admission to the ICU concurrent with CDI diagnosis, or with >2 laboratory or clinical indicators consistent with severe disease, e.g. fever, low albumin, elevated WBC or creatinine. For the case control study, cases and controls were defined as children with severe and non-severe CDI, respectively. Univariate and multivariable analyses were conducted to determine which risk factors were associated with severe disease. For the cohort study, patients with severe CDI, the exposed group, were compared to those with non-severe CDI, the unexposed group, and prospectively followed for eight weeks. Studied outcomes included relapse, defined as recurrence of CDI within 8 weeks, treatment failure, defined as a change in CDI treatment from metronidazole to vancomycin, and complications related to CDI. Logistic regression was used to construct prediction models for the outcomes of interest. Stool samples were also tested for the presence of the NAP1 strain.

Results: We analyzed 82 patients with CDI, of whom 9 (11%) had NAP1+ isolates. The majority of patients (n=45, 55%) had severe CDI. Risk factors for severe disease included presence of malignancy, receipt of 2 or more classes of antibiotics prior to disease onset, and prolonged length of stay (LOS) [adjusted OR (95% CI): 9.94 (1.38, ∞), 5.30 (1.53, 18.30), 1.07 (1.00, .15), respectively]. The relapse rate did not differ between patients with severe (27%) and non-severe (22%) CDI (p-value: ns). There were 2 (4%) treatment failures in patients with severe CDI and 4 (11%) in those with non-severe CDI. Among patients with severe CDI, 11% were diagnosed with pseudomembranous colitis. There was 1 death during the study period. We did not identify any factors associated with relapse. Similarly, NAP1 was not independently associated with severe disease or relapse, although few had NAP1-infection.

Conclusions: We have identified children with malignancy, those who received multiple antibiotic classes, and prolonged LOS as important subgroups at high risk for severe disease. Patients with severe CDI made up the majority of our cohort, although complications were infrequent. Relapse rates were similar to those reported in adults.