Liposomal amphotericin B as early empiric antimycotic therapy of pneumonia in granulocytopenic patients
Authors: Böhme Angelika , Hoelzer D. 
Published: April 2009

Summary. 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 mgkg‐1 in patients with pneumonia but without radiological signs or other evidence of Aspergillus infection and 5 mgkg‐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 mgkg‐1 in cases of proven/probable aspergilloses. Six out of seven (86%) patients without initially suspected aspergilloses receiving AmBisome 3 mgkg‐1 responded completely. Twelve out of 16 patients with initial radiological signs of aspergillosis receiving AmBisome 5 mgkg‐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 mgkg‐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 AmBisometreated 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 mgkg‐1 and 5 mgkg‐1 on alternate days was well tolerated and greatly reduced the lethality of proven/probable Aspergillus pneumonias.

Zusammenfassung. Dreiundzwanzig granulozytopenische Patienten mit hämatologischer Systemerkrankung und fieberhaften pulmonalen Infiltraten erhielten zusätzlich zu Breitspektrumantibiotika eine empirische antimykotische Therapie mit liposomalem Amphotericin B (AmBisome®). AmBisome wurde jeden 2. Tag in zwei verschiedenen Dosierungen gegeben: 3 mgkg‐1 bei Pneumonien ohne Hinweis auf eine Aspergillus‐Infektion, 5 mgkg‐1 bei Pneumonien mit Verdacht auf Aspergillus‐Infektion. Hauptstudienziele waren der Vergleich der Letalitäat bei Pneumonien unter früher empirischer Therapie mit niedrig dosiertem AmBisome mit einer historischen Gruppe, bei der die antimykotische Therapie mit konventionellem Amphotericin B erst mit Nachweis bzw. dringendem Verdacht auf eine Aspergillus‐Pneumonie begonnen wurde sowie Effektivität und Verträglichkeit von AmBisome 5 mg kg‐1 bei