Abstract
In Japan, only a few antifungal agents have
been approved for children, but in actual clinical practice,
various antifungal agents used in adults are administered to
pediatric patients with invasive fungal infections (IFIs).
However, the pediatric dosages of some antifungal agents
are not indicated in the package inserts or mentioned in the
Japanese Mycology Study Group 2007 Guidelines for
Management of Deep-seated Mycoses. We conducted a
nationwide survey to determine how antifungal agents are
being used to treat pediatric patients with IFIs in Japan. We
sent a questionnaire to 792 medical centers that train
pediatricians and received 250 (31.6 %) responses. In the
past 5 years, 65 (26.0 %) of 250 facilities reported treating
a total of 232 cases of IFIs. The characteristics of pediatric
patients with IFIs were almost the same as adult patients
except that immunological diseases and neonatal diseases
are common as underlying diseases. Antifungal agents used
in adults were all used in children. However, the dosages of
some antifungal agents deviated from the package insert or
guideline recommendations. As for the reasons for selecting
a particular antifungal agent, strong antifungal activity
(including potency, broad spectrum, and clinical efficacy)
was favored over safety. These results can be used to revise
guidelines for the management of children with IFIs.
Keywords Nationwide Survey Questionnaire
Invasive fungal infections Antifungal agents
Introduction
Invasive fungal infections (IFIs) are a major cause of
morbidity and mortality in immunocompromised patients
[1–3]. IFIs often occur in children with various reasons for
increased susceptibility to infections, including immature
immune systems [4, 5]. Recently, the incidence of IFIs in
children has increased with expanded pediatric use of
therapies such as intensive chemotherapy, hematopoietic
stem cell transplantation, or both for leukemia, and
immunotherapy with steroids or immunosuppressants [6].
Early diagnosis of IFIs is challenging in children, not only
because there are few characteristic symptoms in patients
with severe underlying diseases, but also because of the
invasive nature of diagnostic examinations for IFIs [7].
Although several new antifungal agents have been developed
during the past decade, not all of these agents have
been approved for children in Japan. Accordingly, the
pediatric dosages of some antifungal agents are not indicated
in their package inserts, and they are not mentioned
in the Japanese Mycology Study Group 2007 [8] Guidelines
for Management of Deep-seated Mycoses (Japanese
guideline). We thought it was necessary to determine the
actual status of antifungal agent usage in children.
The present survey was conducted to determine how
antifungal agents are being used to treat pediatric patients
with IFIs in Japan. The results can be used to revise
guidelines for management of children with IFIs.
Patients and methods
A questionnaire with the following three questions was sent
to medical centers that train pediatricians in September
2009: