JAC Advance Access originally published online on November 12, 2003
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Journal of Antimicrobial Chemotherapy (2003) 52, 1032-1034
© 2003 The British Society for Antimicrobial Chemotherapy
Efficacy of high doses of liposomal amphotericin B in the treatment of experimental aspergillosis
Infectious Diseases Research Laboratory, Infectious Diseases Division, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
17 March 2003; returned 25 May 2003; revised 26 September 2003; accepted 3 October 2003
Objective: Differences in efficacy between deoxycholate amphotericin B (d-AmB) and escalating doses of liposomal amphotericin B (L-AmB) were evaluated in a model of invasive pulmonary aspergillosis in persistently steroid-immunosuppressed rats.
Methods: Animals were infected intratracheally with a conidial suspension of a clinical isolate of Aspergillus fumigatus and randomized to receive intravenously 5% dextrose, 1 mg/kg/day of d-AmB or 3, 5 or 10 mg/kg/day of L-AmB.
Results: All the antifungal treatments improved survival, although no differences were found among the groups, perhaps because of treatment-related toxicity. In animals surviving long enough to receive at least five doses of antifungal treatment, there were significant reductions in paired lung weight in the 5 and 10 mg/kg/day L-AmB groups as compared with the controls (P = 0.004 and 0.001, respectively) and with the 3 mg/kg/day L-AmB group (P = 0.007 and 0.002, respectively). Significant decreases in fungal biomass, measured indirectly by chitin quantification, were found only in the 10 mg/kg/day L-AmB group as compared with controls (P = 0.003), d-AmB (P = 0.007) and 3 mg/kg/day L-AmB (P = 0.001).
Conclusion: Infusion of L-AmB doses as high as 10 mg/kg/day may be a good therapeutic option for the management of invasive pulmonary aspergillosis developing in the context of steroid immunosuppression, although further studies are needed to assess this approach.
Keywords: antifungal treatment, efficacy, invasive pulmonary aspergillosis
* Correspondence address. Servei de Malalties Infeccioses, Hospital General Vall d’Hebron. Passeig Vall d’Hebron, 119–129, 08035 Barcelona, Spain. Tel: +34-93-4894033; Fax: +34-93-2746057; E-mail: jgavalda{at}vhebron.net
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