Efficacy of high doses of liposomal amphotericin B in the treatment of experimental aspergillosis

María Teresa Martín, Joan Gavaldà, Pedro López, Xavier Gomis, José Luís Ramírez, Dolors Rodríguez, Oscar Len, Queralt Jordano, Isabel Ruiz, Marta Rosal, Benito Almirante, Albert Pahissa

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16 Citations (Scopus)

Abstract

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, werefound 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.
Original languageEnglish
Pages (from-to)1032-1034
JournalJournal of Antimicrobial Chemotherapy
Volume52
Issue number6
DOIs
Publication statusPublished - 1 Dec 2003

Keywords

  • Antifungal treatment
  • Efficacy
  • Invasive pulmonary aspergillosis

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