Invasive fungal infections in lung transplantation: role of aerosolised amphotericin B

Abstract

Immunocompromised patients, especially solid organ transplant (SOT) and hematopoietic stem cell transplant recipients, have a high morbidity and mortality rate as a result of invasive fungal infections (IFIs). Therefore, effective and correct prophylaxis of these IFIs continues to be an important issue in these patient populations. Fungal infections in the lung are most often due to Aspergillus spp., but other non- Aspergillus moulds such as Mucor spp. can also cause pulmonary infections. Lung transplant recipients have the highest incidence of invasive aspergillosis of all SOT patients. Prophylaxis should consider the risk factors affecting each group of patients. As the lung is the target organ of most fungal infections due to moulds, aerosolised antifungal prophylaxis has been potentially considered to be a safe and effective strategy. Administration of a nebulised antibiotic achieves high local concentration of the drug, avoiding undesirable systemic effects and drug interactions. The use of aerosolised amphotericin B (AmB) as prophylaxis or co-adjuvant treatment for pulmonary fungal infections has been reported in several groups of immunosuppressed patients. Lipid formulations of AmB penetrate the lung better and have a longer half-life than amphotericin B deoxycholate (ABD). Prophylaxis with aerosolised lipid-based AmB products has several advantages over ABD: it can be administered at much longer intervals and is equally effective and better tolerated. Although several studies have been published using aerosolised AmB both as deoxycholate and lipid formulations, available data remain inconclusive owing a lack of standardisation of administration procedures and doses.