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.

Antifungal Therapy in ‘Bone Marrow Failure’

“…Should the conventional formulation be contraindicated, one of the lipid‐complexed formulations should be used instead ( Bohme & Hoelzer, 1996). For example, in a Europe‐wide, randomized, double‐blind comparative trial of the liposomal formulation of amphotericin B (AmBisome) versus conventional amphotericin B (cAMB) in the empiric treatment of both paediatric and adult febrile neutropenic patients AmBisome (3 mg/kg/d) was as effective as cAMB in the prevention of proven treatment‐emergent fungal infections ( Prentice et al , 1997 ).…”

It only takes one to do many jobs: Amphotericin B as antifungal and immunomodulatory drug

“…Unfortunately, this formulation is highly nephrotoxic and shows side effects as fevers, malaise, weight loss, headache, hypotension, abdominal pain, nausea, vomiting, diarrhea, normochromic normocytic anemia, and myalgia (Sabra and Branch, 1990; Meunier et al, 1991; Ringden et al, 1991; Gulati et al, 1998; Laniado-Laborin and Cabrales-Vargas, 2009). For this reason, new formulations have been introduced in the last years (Lopez-Berestein et al, 1985; Bohme and Hoelzer, 1996; Gulati et al, 1998; Rust and Jameson, 1998; Walsh et al, 1998; Dupont, 2002). The new presentations have reduced toxicity because they are lipid-carried presentations.…”

Review of comparative studies between conventional and liposomal amphotericin B (Ambisome®) in neutropenic patients with fever of unknown origin and patients with systemic mycosis

“…So far, the effectiveness of liposomal amphotericin B in the treatment of fungal infection has been shown in retrospective studies until last year [ 12–17].…”

“…With respect to pharmacokinetics, plasma levels of amphotericin B will be increased significantly. A decrease in the volume of distribution goes along with a prolonged circulation in the bloodstream [ 11–18]. Due to its small particle size AmBisome ® can escape immediate clearance by the monocyte–macrophage system.…”