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


Between 2000 and 2006 inclusive, data from approximately 1.8 million inpatients were reported to PHIS from 25 pediatric hospitals studied (Figure 1) of which 62,843 (3%) were prescribed at least 1 dose of an antifungal agent.

Selection of Study Population.

Demographic data are displayed in Table 1 . The median age of patients requiring antifungal therapy was 5.8 years (IQR: 1.2, 12.7) and the median length of stay was 11 days (IQR: 4, 31). A total of 5144 patients died during their hospitalization (8%). There were 49,411 patients (79%) who had an underlying condition as defined by CCC or APR-DRG, with 32% diagnosed with more than one condition. The most common underlying condition for the cohort was malignancy (42%), followed by hematologic or immunologic deficiency (16%), and cardiovascular condition (15%). Overall, fluconazole was the most commonly prescribed antifungal agent (76%), followed by amphotericin preparations (26%).

During the study period, there was a significant increase in the number of inpatients who were prescribed antifungal therapy, from 32 per 1000 hospitalizations in 2000 to 38 per 1000 hospitalizations in 2006 (P = 0.03).

There was a significant decrease in the utilization of AMB, itraconazole, and flucytosine (P = 0.02, P = 0.03, and P = 0.02, respectively) (Figure 2). The utilization of both voriconazole and the echinocandins (caspofungin and micafungin) significantly increased (P = 0.02 and P = 0.02, respectively). The increase in echinocandin utilization was almost entirely attributable to the use of caspofungin during this study period, as the first prescriptions of micafungin were reported in 2006. Prescribing of fluconazole remained relatively constant, and LFAB use also increased, although this increase was not statistically significant (P = 0.20).

Trends in antifungal therapy among 62,843 pediatric inpatients, 2000-2006.

Among 62,843 inpatients who received an antifungal agent, there were 14,262 patients (23%) diagnosed with a fungal infection: mucosal/superficial candidiasis (14%), disseminated/systemic candidiasis (5%), aspergillosis (1%), endemic mycoses (1%), zygomycosis (<1%), and other fungal infections (2%). There was no statistical difference in the number of fungal infections that occurred during the study period. AMB was more commonly given to those who had a fungal infection diagnosis (16% versus 10%, P < 0.0001). Prescriptions for LFAB increased during the study period for those with a diagnosis of fungal infection (14% in 2000-2001 compared with 17% in 2005-2006, P = 0.0001).

There were 48,581 patients that were prescribed antifungal agents who did not receive a fungal diagnosis. Although we are unable to determine the indication for prescription, we assume the use was either preemptive or prophylactic.

Candidiasis. A total of 11,671 pediatric patients (age <18 years) (19%) were diagnosed with a form of candidiasis during the study period.

Mucosal/Superficial Candidiasis. There were 8715 patients (14%) diagnosed with mucosal/superficial candidal infections. The most commonly prescribed agent for these patients was fluconazole (89%), followed by LFAB (11%). During the study period, use of AMB for the treatment of mucosal/superficial candidiasis decreased from 23% in 2000-2001 to 2% in 2005-2006 (P < 0.0001).

Disseminated/Systemic Candidiasis. There were 2956 patients (5%) diagnosed with disseminated/systemic candidiasis. Fluconazole was the most commonly prescribed antifungal agent for inpatients with disseminated/systemic candidiasis (61%), followed by LFAB (42%). During the study period, there were significant changes in prescribing for inpatients (Figure 3A). AMB was used to treat 65% of inpatients in 2000-2001, but only 11% of cases received the drug in 2005-2006 (P < 0.0001). In 2000-2001, 24% of all amphotericin preparations prescribed for disseminated/systemic candidiasis were LFAB, whereas in 2005-2006, 77% were LFAB. The echinocandins significantly increased in prescription for the treatment of disseminated/systemic candidiasis, from 0% in 2000-2001 to 23% in 2005-2006 (P < 0.0001).

A, Trends in antifungal therapy for disseminated systemic candidiasis. B, Trends in antifungal therapy for aspergillosis.

Aspergillosis. There were a total of 1002 patients who were diagnosed with aspergillosis (2%). The most common antifungal agents prescribed for patients with aspergillosis were voriconazole (43%) and LFAB (42%). In 2000-2001, 43% of all amphotericin preparations prescribed for aspergillosis were LFAB, while in 2005-2006, 92% were LFAB. All antifungal agents except fluconazole demonstrated significant changes in utilization over the study period (Figure 3B).

During the study period, there were 5839 neonatal hospitalizations requiring at least 1 dose of an antifungal agent. There was a significant increase in the number of neonatal patients treated with antifungal therapy during the 7-year period (P = 0.03). Fluconazole was the most commonly prescribed antifungal agent in neonates (65%), followed by AMB (30%) and LFAB (20%). The use of fluconazole and the echinocandins in neonates significantly increased during the study period (P = 0.03 and P = 0.04, respectively), whereas the use of AMB and flucytosine decreased over the same time period (P = 0.02 and P = 0.02, respectively) (Figure 4).

Trends in antifungal therapy for neonatal hospitalizations, 2000-2006.

A total of 1247 (21%) neonates were diagnosed with a fungal infection, most commonly a form of candidiasis (86%). Mucosal/superficial candidal infections accounted for 442 (35%) neonatal fungal infections, which were most commonly treated with fluconazole (71%), AMB (36%), and LFAB (15%). Disseminated/systemic candidiasis accounted for 631 (51%) neonatal fungal infections. AMB was used most commonly to treat these neonates (54%), followed by fluconazole (50%). Prescribing of AMB, LFAB, and the echinocandins for the treatment of neonatal disseminated/systemic candidiasis changed significantly during the study period. In 2000-2001, 14% of all amphotericin preparations prescribed were LFAB, while in 2005-2006, 63% were LFAB.


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