1184 infection control & hospital epidemiology october 2015, vol. 36, no. 10


freestanding children’s hospitals across the United States. The PHIS hospitals are 43 of the largest children’s hospitals in America. These hospitals represent 17 of 20majormetropolitan areas in the United States. Data elements present in the PHIS database include demographics, insurance information, International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure and diagnosis codes, and resource utilization data including billing data for pharmacy, imaging, and clinical services. Our analysis was limited to the 41 hospitals that provided all data elements during the study period.


Study Population


Children aged 1–18 years discharged from PHIS hospitals between January 1, 2006 and August 31, 2011 were eligible for inclusion in the study. Patients hospitalized for <3 days were excluded from the analysis. Children with CDI were identified using a previously validated case-finding tool10 that included the presence of an ICD-9-CM code due to Clostridium difficile (008.45) plus a billing charge for a C. difficile test. Hospital onset (HO) CDI was defined as a C. difficile test ≥3 days after hospital admission. Community onset (CO) CDI was defined as a C. difficile test prior to hospital day 3. The day of admission was defined as day 0. Only the first CDI-related hospitalization for each patient was used in the analysis.


Outcomes


The primary outcome for the study was all-cause in-hospital mortality occurring during an index admission within 30 days of a C. difficile test. CDI-related readmission within 8 weeks, the secondary outcome, was defined as a subsequent admis- sion within 8 weeks of the initial C. difficile test date that included both a C. difficile test charge within 48 hours of admission and receipt of CDI-directed therapy (ie, metroni- dazole or oral vancomycin).


Data Collection


All data utilized for this study were obtained from the PHIS database. Demographic and clinical information collected for each patient included age, sex, race, presence and type of comorbid condition, and in-hospital medication exposures including antimicrobial agents, proton pump inhibitors, H2 blockers, and total parenteral nutrition. Receipt of antibiotics 90 days prior to CDI was classified in 2 ways: (1) the presence of any antibiotics represented as yes/no and (2) the total number of antibiotic classes. Treatment for CDI was defined as the receipt of metronidazole or oral vancomycin. The presence and type of comorbid condition was classified using a pre- viously validated classification system that groups ICD-9-CM diagnostic codes into pediatric chronic conditions.11 Data collected on underlying severity of illness included admission to the intensive care unit (ICU) and receipt of respiratory


support (supplemental oxygen or mechanical ventilation) or pressor support (dopamine, epinephrine, dobutamine, or norepinephrine).


Statistical Analysis


Summary statistics were constructed using frequencies for categorical variables and medians for continuous variables. Categorical variables were compared using the Pearson χ2 test or Fisher’s exact test when appropriate, and continuous variables were compared using the Wilcoxon rank-sum test. Univariate analyses, using simple logistic regression, were conducted to identify potential risk factors for in-hospital death or CDI- related readmissionamong children withCDI. All variables with P<.05 in the univariate analysis were included in the final multivariable logistic regression model. The number of inpa- tient deaths among the cohort limited the number of potential risk factors included in the finalmultivariablemodel. Therefore, to characterize the underlying severity of illness, a composite severity of illness variable was created from the following data elements: admission to the ICU, receipt of pressor support, or receipt of respiratory support in the 48 hours prior to the C. difficile test. The severity of illness variable ranged from a score of 0 to 3, 0 representing a patient with an absence of all severity of illness markers and 3 representing a patient with all 3 markers. Using the final multivariable model, we derived predictions of the probability of death for each factor and combinations of factors that were independently associated with in-hospitalmortality. All analyses were performed using SAS 9.3 (SAS Institute, Inc., Cary, NC) or Stata 12.1 (Stata Corp., College Station, TX).


results Patient Characteristics


We identified 7,318 children with CDI that met our inclusion criteria during the study period. Table 1 displays the characteristics of these children. Median age of patients with CDI was 6 years [interquartile range (IQR), 2–13]. The majority of children (51.8%) were male, had at least 1 comorbid condition (74.9%), were classified as CO-CDI (52.9%), had gastric acid suppression (GAS) within 30 days prior to C. difficile test (58.6%), and received an antibiotic within 90 days prior to their C. difficile test (74.9%).


Primary Outcome: Risk Factors for In-Hospital Mortality


Among the study cohort, 109 (1.5%) children with CDI died in the hospital within 30 days of their C. difficile test. Univariate analysis identified several potential risk factors associated with in-hospital mortality (Table 2). These potential factors include age, severity of illness markers, number of classes of antibiotics received within 30 days prior to C. difficile test, GAS (receipt of proton pump inhibitors or H2 blockers) within 30 days,


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