Remarkably efficient inhaled antifungal monotherapy for invasive pulmonary aspergillosis: Figure 1–

Remarkably efficient inhaled antifungal monotherapy for invasive pulmonary aspergillosisTo the Editors: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 -1 and, although higher concentrations (.5.5 mg?mL -1 ) 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aspergillosis was treated with systemic voriconazole, but due to unacceptable adverse effects, the treatment had to be withdrawn.With no other conventional treatment options, inhaled voriconazole was administered.