5PSQ-043 Nebulised voriconazole in lung transplant recipients: analysis of use, efficacy and tolerability

Background Fungal infection is a significant source of morbidity and mortality in lung-transplant recipients (LTR). To avoid systemic toxicity, various nebulised antifungal agents are used after transplant to prevent or treat invasive fungal infections (IFI). Nebulised liposomal amphotericin B (n-LAB) has been widely used. However, some fungal agents, such as Scedosporium spp. with reduced amphotericin susceptibility, are emerging. Thus, new antifungal drugs are required. Purpose To evaluate prescription profile, efficacy and tolerability of nebulised voriconazole (n-V) administered at a dose of 40 mg twice-daily in LTR in a tertiary hospital. Material and methods Observational, retrospective study of patients who underwent lung transplant (LT) between January 2008 and September 2017 who received n-V. Data collected from electronic health records were age at LT, cause of transplantation, post-transplant fungal isolations in bronchoalveolar lavage, bronchial suction or sputum, n-LAB use, n-V treatment duration, and adverse effects and efficacy in terms of fungal infection resolution or culture negativity. Results Eleven LTR received n-V , average age 40 (20–66). Causes of transplantation were: six diffuse parenchymal lung disease (DPLD), four cystic fibrosis (CF) and one chronic obstructive pulmonary disease (COPD). Ten patients (91%) previously received n-LAB as antifungal prophylaxis in the post-transplant period. Fungal isolations observed in LTR who received n-V were: Aspergillus Terreus (two), Aspergillus Fumigatus (two), Paecilomyces Lilacinus (three), Scedosporium Apisopermum (three), Scedosporium Prolificans (one) and Scedosporium Aurantiacum (one). There were five cases (46%) of fungal pulmonary infection, three (27%) of airway colonisation, two (18%) IFI and one (9%) S. Apiospermum mycetoma. Average treatment duration was 9.5 months (SD: 6) and no adverse effects were reported. Culture negativity took place in 82% of cases and there was one exitus related to S. Apiospermum and S. Prolificans IFI with n-V therapy duration of 9 months. Conclusion Nebulised voriconazole seems to be an effective alternative to prevent and treat fungal infections when n-LAB antifungal spectrum is not adequate to airway isolations. That occurs in most Scedosporium spp., Paecilomyces spp. and some Aspergillus spp. Its tolerability is good, although n-V is not commercially available and it is prepared from intravenous vials. Further studies will be required to accurately assess the use of n-V in clinical practice. No conflict of interest