INTRODUCTION
Aspergillus spp . can cause different diseases, depending on the
host immune system status. Invasive pulmonary aspergillosis (IPA) is a
serious disease affecting patients with prolonged neutropenia,
transplantat recipients and those receiving long-term treatment with
high doses of corticosteroids, among others (1). Even antifungal
prophylaxis is indicated in vulnerable patients, an increase of fungal
infections prevalence and severity has been observed. Lung transplant
(LT) recipients are especially vulnerable to IPA (2), a prevalence of
6.5% and mortality rate of 52% has been reported in this population
(3). Other non-immunosuppressed patients, such as those with cystic
fibrosis (CF), can be affected by Aspergillus spp. ; it has been
reported that more than 50% of respiratory cultures from CF patients in
a year were positive and about 10% of the patients developed allergic
bronchopulmonary aspergillosis, related to airway damage and respiratory
function alterations (4,5). Even if azole treatment has shown positive
results in CF, treating Aspergillus spp . colonization in this
population remains controversial due to the need of long treatments
related to drug interactions, toxicity and the emergence of antifungal
resistance.
Voriconazole is the primary treatment for IPA; it is available in oral
and intravenous pharmaceutical forms. Other antifungal drugs such as
amphotericin, itraconazole, posaconazole and echinocandines can be added
to the treatment or used as alternatives in case of treatment failure
(6). IPA management usually involves long systemic antifungal treatments
that lead to high rates of adverse events including liver, kidney and
medullar toxicities; moreover, these therapies are usually involved in
major drug-drug interactions with clinical implications and their
pharmacokinetic profile is difficult to predict due to pharmacogenetic
diversity among the population (7,8). Finally, treatment efficacy
depends on the drug distribution to the lung and the epithelial lining
fluid that coats the bronchoalveolar epithelium; however, it has been
observed that the distribution of antifungal drugs to the biophase might
be limited by their physicochemical properties in some cases (9).
In this context, antifungal administration through the pulmonary route
has been suggested in order to ensure therapeutic concentrations of drug
in the biophase and increase treatment efficacy, avoid adverse events
and prevent drug-drug interactions. Even if there are not commercial
antifungal pharmaceutical presentations for pulmonary administration
currently, vials of liposomal amphotericin B and amphotericin B
deoxycholate for intravenous administration have been widely used for
nebulization in prophylaxis and treatment of pulmonary aspergillosis;
this approach has been proved to be a safe and effective (10).
There is little evidence about voriconazole administration via
nebulization. The goal of this study is to characterize the compounded
voriconazole solution for nebulization and describe the use of nebulized
voriconazole in our center.