Remarkably efficient inhaled antifungal monotherapy for invasive pulmonary aspergillosis.

Voriconazole is a broad-spectrum antifungal agent that is effective against moulds such as Aspergillus fumigatus. It inhibits the cytochrome P450-dependent 14-a–lanosterol demethylase, preventing the conversion of lanosterol to ergosterol. This results in the accumulation of toxic methylsterols in the fungal wall and the inhibition of fungal growth [1]. Voriconazole is available as an intravenous infusion solution containing a cyclodextrin molecule (Captisol1; Ligand Pharmaceuticals Inc., La Jolla, CA, USA) to increase its solubility in water [2]. Adverse effects, such as gastrointestinal disorders, visual disturbances and elevated transaminase levels, complicate the use of voriconazole if used systemically. The therapeutic concentration range of voriconazole is from 1 to 5.5 mg?mL and, although higher concentrations (.5.5 mg?mL) are associated with better clinical outcomes, they are also associated with more severe and less common side-effects, including encephalopathy and hallucinations [1]. Inhaled voriconazole reduces histological manifestations of invasive aspergillosis in rodents [3] and it has been proposed that a favourable lung tissue to plasma concentration ratio is obtained through this route of administration [4]. Consequently, inhaled voriconazole may provide higher concentrations at the site of infection without increasing the risk of systemic side-effects. We present three cases in which life-threatening invasive aspergillosis was treated with systemic voriconazole, but due to unacceptable adverse effects, the treatment had to be withdrawn. With no other conventional treatment options, inhaled voriconazole was administered.