Impact of Prophylaxis with Aerosolized Amphotericin-B Deoxycholate (d-AmB) on Respiratory Tract Invasive Fungal Infections (IFIs) after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).

Background and aims IFIs still pose major challenges in HSCT, and effective prophylaxis remains a matter of debate. The aim of this retrospective study was to evaluate the impact of aerosolized d-AmB on respiratory tract IFIs in a homogeneous cohort of allogeneic HSCT patients, transplanted at our institution. Patients and methods Since 1999, 81 consecutive patients were transplanted from matched related (N=61) or unrelated donor (MUD). Analysis was performed on 74 evaluable patients, in order to monitor the prevalence of respiratory tract IFIs within 40 days after HSCT, according to current guidelines (possible, probable, proven IFIs). Conventional antifungal prophylaxis was based on the association of fluconazole (400 mg/d), plus aerosolized d-AmB (15 mg bid) in 54 out of 74 cases (73%). All the patients were screened before transplant and monitored thereafter with CT or x-rays (paranasal sinuses, thorax), surveillance swabs and galactomannan antigenemia. Chi square test was performed to evaluate correlations between variables.

Results Aerosolised d-AmB was administered to 70 patients for a median time of 15 days (range 1–45). Prolonged administration was not associated with increased severe bacterial infections, nor severe adverse events were observed; only a patient developed moderate bronchial spasm. In 13 pts, aerosolized d-AmB was delivered for less than 7 days, due to worsened clinical conditions, or poor compliance. In this group, proven IFIs were diagnosed in 2 patients (1 mucormycosis and 1 fusariosis), possible aspergillosis in one and probable aspergillosis in another one. A shortened administration (<7 days) of aerosolized d-AmB was associated with an increased risk of IFIs (p=0,002). Overall, 95% of patients did not experience IFIs and nobody died due to IFIs. Nine patients had a pre-transplant nasal swab positive for Aspergillus spp., and 8 of them received Aerosolized d-AmB; subsequent surveillance swabs proved negative. On the other hand, the only patient with positive swab who was not able to receive aerosolized d-AmB due to bronchial spasm developed a possible aspergillosis.

Discussion Despite the low number of patients, prolonged aerosolized d-AmB seems to play a role in preventing respiratory tract IFIs, but a randomised controlled trial is recommended to verify the impact of this prophylaxis in the setting of allogeneic HSCT.