LIPOSOMAL AMPHOTERICIN-B AS EARLY EMPIRIC ANTIMYCOTIC THERAPY OF PNEUMONIA IN GRANULOCYTOPENIC PATIENTS

Twenty-three neutropenic patients with haematological malignancies and febrile pulmonary infiltrates were empirically treated with liposomal amphotericin B (AmBisome(R)) in addition to broad-spectrum antibiotic s. AmBisome was given on alternate days in two different dosages: 3 mg kg(-1) in patients with pneumonia but without radiological signs or o ther evidence of Aspergillus infection and 5 mg kg(-1) in pneumonia pa tients with suspected Aspergillus infection. The main objectives of th is study were to compare the response and lethality of pneumonias trea ted early with empirically AmBisome with a historical group (treatment with conventional amphotericin B only in case of proven/highly probab le aspergillosis) and to investigate the tolerability and efficacy of AmBisome 5 mg kg(-1) in cases of proven/probable aspergilloses. Six ou t of seven (86%) patients without initially suspected aspergilloses re ceiving AmBisome 3 mg kg(-1) responded completely. Twelve out of 16 pa tients with initial radiological signs of aspergillosis receiving AmBi some 5 mg kg(-1) were evaluable. Body temperature normalized in 10/12 (83%)patients; eight experienced complete and two partial regression o f their infiltrations and 9/10 patients with proven/probable aspergill osis responded. Acute AmBisome-related reactions were seen in three pa tients from each group; loss of potassium was noted in five subjects i n each group and slightly increased plasma creatinine was found in two patients in the 5 mg kg(-1) group. Altogether, the response of all pn eumonia patients treated with early empirical AmBisome compared with t he 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=0.0 08) patients responded. Pneumonia lethality was 1/19 in the AmBisome-t reated 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 tre atment 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 A spergillus pneumonias.