Liposomal amphotericin B in the treatment of fungal infections in neutropenic patients: a single‐centre experience of 133 episodes in 116 patients

Abstract

Liposomal amphotericin B (AmBisome) was used for suspected or confirmed fungal infection complicating 133 neutropenic episodes in 116 patients not tolerating, or not responding to, conventional amphotericin. Adverse effects were infrequent and no significant renal impairment resulted. Acute reactions occurred in five patients, reversible hepatic dysfunction in 23, and hypernatraemia in 17. The putative mycosis resolved with AmBisome treatment in 81 episodes (61%) and progressed with fatal outcome in 25 (19%), but the diagnosis was equivocal in most, and in 27 episodes (20%) evidence indicating nonfungal pathogenesis emerged. Treatment efficacy is, however, evaluable in those with proven aspergillosis. 13/17 patients with confirmed invasive aspergillosis responded to AmBisome (77%), conventional amphotericin having failed in 11. Treatment was successfully discontinued when the neutrophil count was < 1 x 10(9)/l in eight responders (61%). In four further patients treated for suspected aspergillosis, disseminated infection was documented at post-mortem, but the true incidence is unknown. This analysis confirms that AmBisome is well tolerated and effective against invasive mycoses in neutropenic patients, and may salvage patients when conventional amphotericin proves excessively toxic or ineffective.

Eficiência terapêutica das formulações lipídicas de anfotericina B

“…Em alguns estudos, AmBisome foi administrado em indivíduos que não toleraram ou não responderam às doses terapêuticas de AB-DOC (Coker et al, 1991;Hudson, Scott, Warnock,1991;Ringdén et al, 1991;Mills et al, 1994).…”

“…Neste sentido, a administração de AmBisome resultou em sucesso no tratamento de candidíase hepática num paciente leucêmico (Hudson, Scott, Warnock,1991), de criptococose disseminada em 3 pacientes HIV-positivo (Schürmann et al, 1991), de aspergilose pulmonar em 13 pacientes neutropênicos (Mills et al, 1994), de infecções fúngicas invasivas causadas por Candida spp. e Aspergillus spp.…”

“…Em termos gerais a formulação foi bem tolerada e a indução de toxicidade ocorreu em poucos dos pacientes observados, sendo que em alguns casos não ficou estabelecido se as alterações foram devidas ao tratamento ou à vigência de outras doenças graves. Os efeitos colaterais mencionados foram aumento de creatinina sérica (Schürmann et al, 1991;Tollemar et al, 1993); náusea persistente, febre, calafrios e tremores (Mills et al, 1994;Chopra et al, 1991) ocorreram em pouquíssimas ocasiões. Estudos mais recentes também relataram diminuição de efeitos colaterais, tais como: dispnéia, hipotensão e taquicardia, bem como baixa ocorrência de hipocalemia e de aumento da creatinina sérica (Prentice, Hann, Herbrecht, 1997;Klastersky, 2004).…”

A prospective randomized controlled trial comparing PCR-based and empirical treatment with liposomal amphotericin B in patients after allo-SCT

“…The encapsulation of amphotericin B into the membrane of liposomes offers an interesting approach to reduce toxicity while maintaining or even enhancing efficacy. 15,16 A randomized double-blind trial comparing liposomal amphotericin B (Gilead Sciences, Martinsried, Germany) with conventional amphotericin B in 787 patients with fever of unknown origin showed similar efficacy in both groups, but fewer breakthrough fungal infections and less nephrotoxicity in patients receiving liposomal amphotericin B. 17 In a further randomized study, liposomal amphotericin B in the empirical setting of fever of unknown origin was shown to be effective even at a dose level of l mg/kg body weight.…”

Liposomal amphotericin (AmBisome) is safe in bone marrow transplantation for primary immunodeficiency

“…5 The lack of nephrotoxNo significant changes in ALT levels were observed during AmBisome treatment.…”