Pediatric Antifungal Utilization: New Drugs, New Trends

Priya A. Prasad, MPH; Susan E. Coffin, MD, MPH; Kateri H. Leckerman, MS; Thomas J. Walsh, MD; Theoklis E. Zaoutis, MD, MSCE


Pediatr Infect Dis J. 2008;27(12):1083-1088. 

In This Article


Data Source and Study Population

Data for this study were obtained from the Pediatric Health Information System (PHIS), an administrative database that contains inpatient data from 42 freestanding children's hospitals in the United States. These hospitals are affiliated with the Child Health Corporation of America (CHCA, Shawnee Mission, KS), an alliance of children's hospitals. Data quality and reliability are assured through a joint effort between CHCA and participating hospitals. The data warehouse function for the PHIS database is managed by Thomson Healthcare (Durham, NC). For the purposes of external benchmarking, participating hospitals provide discharge data, including demographics, diagnoses, and procedures. In addition, hospitals submit resource utilization data (eg, pharmaceuticals, imaging, and laboratory) to PHIS. Data are de-identified at the time of submission and are subjected to 175 reliability and validity checks before being processed into data quality reports. Information is accepted into the database once classified errors occur less frequently than a criterion threshold. If a hospital's quarterly data are unacceptable according to these limits, the information is rejected and is eligible for resubmission and reevaluation before inclusion in the database once errors are corrected.

Study Design

Our retrospective cohort study included pediatric inpatients (age <18 years) with discharge dates between January 1, 2000 and December 31, 2006. The primary end point for this study was the prescription of an antifungal agent during hospitalization. To determine prescription of the antifungal agents of interest, we accessed the drug utilization data contained in PHIS. Data available included generic drug name, the day of service on which the drug was prescribed, and the charge associated with the drug.

The criterion for inclusion was any child with a charge for one or more of the following systemic antifungal agents: AMB, LFAB (includes liposomal amphotericin B, amphotericin B lipid complex, and amphotericin B colloidal dispersion preparations), fluconazole, itraconazole, voriconazole, flucytosine, caspofungin, and micafungin. Hospitals were excluded from the analysis if they did not contribute pharmacy data for the entire study period to allow for accurate analysis of trends or if there were limitations in data quality.

Determination of Underlying Condition

To identify patients with underlying conditions, we used a diagnostic classification system for pediatric complex chronic conditions (CCCs) based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. This classification system divides ICD-9-CM codes into 9 categories of conditions: neuromuscular, cardiovascular, respiratory, renal, gastrointestinal, hematologic or immunologic, metabolic, malignancy, and genetic or other congenital defects.[15,16] A CCC is a medical condition expected to last at least 12 months, involve either multiple organ systems or just one that requires the utilization of pediatric specialty services, and lead to hospitalization at a tertiary care center. We determined CCC status based on the ICD-9-CM codes present on the discharge record of the hospitalization that included a prescription for antifungal therapy. In addition to CCCs, we used the All Patient Refined-Diagnosis Related Groups (APR-DRGs), version 20, to identify those individuals who were neonates, had received a hematopoetic stem cell transplant, or had received a solid organ transplant. The APR-DRG is a diagnostic grouping system that uses ICD-9-CM codes to categorize patients to assess and compare severity of illness and risk of mortality.[17]

Determination of Status of Fungal Infection

The designation of fungal infection was determined by the presence of an ICD-9-CM code in any diagnostic position for the following conditions: aspergillosis, disseminated/systemic candidiasis, mucosal/superficial candidiasis, endemic mycoses (coccidioidomycosis, histoplasmosis, and blastomycosis), and zygomycosis (Appendix A).

Statistical Analysis

Summary statistics were constructed using frequencies and proportions for categorical data elements and medians and interquartile ranges (IQR) for continuous variables. All analyses were conducted with SAS version 9.1 (Cary, NC) and Stata version 8.0 statistical software (College Station, TX). A P value <0.05 (2-tailed) was considered to indicate statistical significance. All statistical tests for trend were conducted in Stata 8.0 using the nptrend test.

Human Subjects Oversight

The conduct of this study was approved by the Committee for the Protection of Human Subjects at the Children's Hospital of Philadelphia and CHCA.


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