Low‐dose amphotericin for prevention of serious fungal infection following liver transplantation

Abstract

This study advances previously performed clinical studies of antifungal prophylaxis and prospectively evaluates the efficacy of low-dose amphotericin B preparations for the prevention of invasive fungal infection (IFI) in high-risk liver transplant (LT) recipients. High-risk LT patients were recruited and randomised to openly receive intravenously either conventional amphotericin B (amB) at a dose of 15 mg daily, or liposomal amphotericin B (amBisome) 50 mg daily. Prophylaxis was continued until discharge from the intensive care unit (ICU), until patient death, or until time of conversion to high-dose amBisome for treatment of suspected or confirmed IFI. During the study period, 360 adult LTs were performed; 132 patients were eligible for 149 recruitment episodes into the trial, and 83 patients were recruited for 92 episodes. Of the 92, 48 patient episodes were randomised to receive amBisome prophylaxis, and 44 to receive amB. IFI was uncommon, diagnosed for 3 patients in the amBisome group, and for 2 in the amB group. Furthermore, Aspergillus was isolated on a single occasion during 92 episodes of prophylaxis. Fungal colonisation scores did not differ significantly between the 2 groups. There was a significant difference in the rates of survival to ICU discharge between the 2 groups (79.6% amBisome vs. 59.5% amB, P=0.038). Renal function measures including creatinine clearance at commencement and conclusion of prophylaxis, and at 12 months post transplant were not statistically different between the 2 groups. The use of amphotericin B, liposomal or non-liposomal preparations at low doses, for prophylaxis of IFI in high-risk LT patients, is associated with a low incidence of serious fungal infection. In this randomised study, low-dose amBisome prophylaxis was associated with an increased likelihood of successful discharge from the ICU.