Liposomal amphotericin (AmBisome) in the prophylaxis of fungal infections in neutropenic patients: a randomised, double-blind, placebo-controlled study

Liposomal amphotericin (AmBisome) 2 mg/kg three times weekly was compared w ith placebo as prophylaxis against fungal infection in patients undergoing chemotherapy or bone marrow transplantation (BMT) for haematological malign ancies. Prophylaxis began on day 1 of chemotherapy and continued until neut rophils regenerated or infection was suspected. Of 161 evaluable patients, 74 received AmBisome and 87 received placebo. Proven fungal infections deve loped in no patients on AmBisome and in three on placebo (3.4%) (P = NS), S uspected fungal infections requiring intervention with systemic antifungal therapy (usually amphotericin B) occurred in 31 patients on AmBisome (42%) and in 40 on placebo (46%) (P = NS), Suspected deep-seated infections devel oped in 21 (28.3%) and 31 (35.6%) patients, respectively (P = NS), Time to develop a suspected or proven deep-seated infection showed a trend in favou r of AmBisome (P = 0.11). Fifty patients had fungal colonisation (48 with C andida spp, two with Aspergillus spp) of at least one body site during prop hylaxis; 15 patients while receiving AmBisome (20%) and 35 while on placebo (40%) (P < 0.01). Time to colonisation was significantly delayed in the gr oup receiving AmBisome (P < 0.05). Treatment-related toxicity was modest an d no additional toxicity was observed in patients receiving AmBisome, AmBis ome 2 mg/kg three times weekly is safe and reduces fungal colonisation in p atients receiving intensive chemotherapy or BMT. However, despite encouragi ng trends, prophylactic AmBisome did not lead to a significant reduction in fungal infection or in requirement for systemic antifungal therapy.