Predictors of First Recurrence of C. diff in Children

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Predictors of First Recurrence of C. diff in Children

Materials and Methods


We conducted a retrospective cohort study at The Johns Hopkins Children's Hospital from July 2003 to July 2012 to identify all hospitalized patients treated for CDI to assess the recurrence rate and predictors for the first episode of recurrent CDI in children. The primary outcome of interest was recurrent CDI, defined as an episode of CDI occuring ≤ 8 weeks after the onset of a previous episode, provided that CDI symptoms from the earlier episode completely resolved, with or without therapy in accordance with the Society for Healthcare Epidemiology of America (SHEA)/Infectious Diseases Society of America (IDSA) guidelines. A child met criteria for CDI if appropriate clinical symptoms were identified (ie diarrhea defined as ≥3 loose stools/d alone or in combination with other gastrointestinal symptoms as abdominal pain or emesis), the exclusion of other identified causes of diarrhea as well as clinical confirmation of the diagnosis by the treating physician and respective initiation of treatment in the presence of confirmatory laboratory testing. Patients with missing follow-up information after 8 weeks of the initial CDI diagnosis were excluded. Furthermore, we excluded children whose presenting CDI episode was recurrent disease. Relevant demographic, clinical course and treatment data were extracted from medical records. We were able to capture all inpatient and outpatient medical visits and laboratory work performed within the Johns Hopkins Health System. Standard therapies for CDI in children hospitalized at Johns Hopkins Hospital are described elsewhere.

We classified episodes of CDI with respect to healthcare exposure and onset of clinical symptoms. Healthcare Facility-onset Healthcare Facility-associated CDI (HO-HCFA CDI), Community-onset Healthcare Facility-associated CDI (CO-HCFA CDI), Community-associated CDI and "indeterminate" CDI were defined according to standard definitions. The IDSA and SHEA define CDI in adults as severe if peripheral leukocyte count is ≥ 15,000/mm or if serum creatinine increases to ≥ 50% from baseline.

Laboratory Testing


Before June 2009, a 2-step algorithm was applied to identify C. difficile, consisting of screening of stool specimens for C. difficile glutamate dehydrogenase antigen and consecutive cell culture cytotoxicity assay for screen-positive specimens. In June 2009, polymerase chain reaction (BD GeneOhm Cdiff, Sparks MD assay) was introduced.

Statistical Analyses


χ and Fisher's exact test (where appropriate) were used for comparisons of proportions and the Mann-Whitney U test was applied to analyze non-normally distributed continuous variables. All variables found to be significant in univariable analyses were included in the multivariable regression model. The Hosmer-Lemeshow goodness-of-fit test was applied to assess the final model. Two-sided, P-values ≤ 0.05 were considered significant. Analyses were performed using STATA Statistical Software Version 12.0 (Stata Corp., College Station, TX). The Johns Hopkins University School of Medicine Institutional Review Board approved this study with a waiver for patients' informed consent.

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