DISCUSSION
Our study retrospectively describes the use of nebulized voriconazole to
treat IPA in a third referral hospital. Compounded voriconazole solution
for nebulization characteristics are adequate for nebulization, it is
well tolerated and voriconazole is not absorbed into systemic
circulation even in long treatments.
This study has been performed in the real-world setting, allowing the
inclusion of complex patients who represent the potential target
population of this treatment. Even if the sample of patients is limited,
determination of serum concentration of voriconazole has allowed us to
evaluate the rate of voriconazole absorption and the great length of
some of the treatments have provided reliable information about safety.
Literature available about the use of nebulized voriconazole in humans
is scarce. Jolle et al . have reported the use of nebulized
voriconazole in combination with oral treatment in a young patient with
CF to treat a severe pulmonary infection caused by Scedosporium
apiospermum , they concluded that it was safe and effective (18).Â
Hilberg et al . published a series of 3 cases of IPA caused byAspergillus spp. successfully treated with inhaled voriconazole
monotherapy (40 mg every 12-24 hours) (19). Authors reported an adequate
tolerability to voriconazole nebulization, as our results confirm. The
efficacy reported by these case reports is better than we observed in
our study; however, authors’ conclusions should be taken cautiously
since there might be a bias towards publishing only cases with positive
outcomes.
This study has some limitations. First, since it is a retrospective
study, voriconazole plasma concentration was not consistently measured
in all patients so there is missing information. Second, different
excipients contained in each voriconazole brand could have an impact on
treatment toxicity and absorption, even if we did not detect any
differences. Third, patients included were highly complex and some of
them were sedated; thus, our capacity to detect AE might have been
restricted. Finally, due to the limited sample and the absence of a
control group, it is not possible to draw conclusions about treatment
effectiveness.
Our study has shown that voriconazole solution is suitable for
nebulization, it is well tolerated and it is not absorbed into the
systemic circulation even in long treatments. Therefore, the pulmonary
route of administration could be an interesting option to treat complex
pulmonary infections and/or colonizations when preferred treatments are
not efficient, there is toxicity due to systemic treatment or there is
risk of DDI. Further research is needed in order to assess voriconazole
nebulization efficacy to treat specific clinical situations.