Liposomal amphotericin B as early empiric antimycotic therapy of pneumonia in granulocytopenic patients

Abstract

Twenty-three neutropenic patients with haematological malignancies and febrile pulmonary infiltrates were empirically treated with liposomal amphotericin B (AmBisome) in addition to broad-spectrum antibiotics. AmBisome was given on alternate days in two different dosages: 3 mg kg-1 in patients with pneumonia but without radiological signs or other evidence of Aspergillus infection and 5 mg kg-1 in pneumonia patients with suspected Aspergillus infection. The main objectives of this study were to compare the response and lethality of pneumonias treated early with empirically AmBisome with a historical group (treatment with conventional amphotericin B only in case of proven/highly probable aspergillosis) and to investigate the tolerability and efficacy of AmBisome 5 mg kg-1 in cases of proven/probable aspergilloses. Six out of seven (86%) patients without initially suspected aspergilloses receiving AmBisome 3 mg kg-1 responded completely. Twelve out of 16 patients with initial radiological signs of aspergillosis receiving AmBisome 5 mg kg-1 were evaluable. Body temperature normalized in 10/12 (83%) patients; eight experienced complete and two partial regression of their infiltrations and 9/10 patients with proven/probable aspergillosis responded. Acute AmBisome-related reactions were seen in three patients from each group; loss of potassium was noted in five subjects in each group and slightly increased plasma creatinine was found in two patients in the 5 mg kg-1 group. Altogether, the response of all pneumonia patients treated with early empirical AmBisome compared with the historical group was 17/19 vs. 49/72 (89% vs. 68%, NS); among those with proven/probable aspergilloses 11/12 vs. 7/17 (92% vs. 41%, P = 0.008) patients responded. Pneumonia lethality was 1/19 in the AmBisome-treated patients compared with 23/72 in the historical group (5% vs. 32%, P = 0.01); and among those with proven/probable aspergilloses it was 1/12 vs. 10/17 (8% vs. 59%, P = 0.008). In conclusion, early empiric treatment with AmBisome 3 mg kg-1 and 5 mg kg-1 on alternate days was well tolerated and greatly reduced the lethality of proven/probable Aspergillus pneumonias.