JAC Advance Access published online on November 12, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh003
© 2003 by The British Society for Antimicrobial Chemotherapy
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Brief report
1 Infectious Diseases Research Laboratory, Infectious Diseases
Division, Hospital Universitari Vall d’Hebron, Universitat
Autònoma de Barcelona, Barcelona, Spain
* Corresponding author. E-mail: jgavalda{at}vhebron.net.
Received 17 March 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
Efficacy of high doses of liposomal amphotericin
B in the treatment of experimental aspergillosis
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