Efficacy comparison between Liposomal Amphotericin B (L- AmB) and Voriconazole (Vori) in a murine infection model of pulmonary Aspergillus flavus

Ref ID: 19441

Author:

J. A. Olson, D. Hahka, N. Nguyen and J. P. Adler-Moore

Author address:

CA State Polytechnic University, Pomona, USA

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

Objectives Although Aspergillus fumigatus causes 66% of aspergillo-
sis infections, the second most common causative agent is Aspergillus
flavus with an incidence of 14%. A. flavus infections are more difficult
to treat and the present study was done to determine if the combina-
tion of Vori and L-AmB, would be more effective than either drug
alone for treating a murine A. flavus pulmonary infection.
Methods Swiss Webster mice were immunosuppressed with triam-
cinolone d-3, d0 and d+2, intranasally challenged with 8 x 10ex6 A.
flavus (ATCC #203403) and 2 hours later treated with 10 mg/kg L-
AmB (IV, qd), 40 mg/kg Vori (PO, bid), 10 mg/kg L-AmB (IV qd) +
40 mg/kg Vori (PO,bid) or 5% dextrose (D5W) (n = 17/group). At
48 hours post-challenge, mice (n = 7/group) were euthanized and
blood collected for BUN. At this same timepoint, BAL and lungs were
harvested for fungal burden (Log10 CFU/g), drug concentration
(amphotericin B bioassay), and cytokine levels (multiplex bead
assay). Mice (n = 10/group) were monitored for survival, weight
change and disease signs to d+21.
Results Long-term survival to d+21 was significantly better with L-
AmB alone or L-AmB + Vori compared to Vori (100% vs 40%,
p = 0.01) with disease signs and weight loss paralleling the survival
data. Day +2 (24 h post-2nd L-AmB dose; 12 h post-4th Vori dose)
the fungal burden in the BAL was significantly lower with L-AmB vs
all other treatments (p  0.05). In the lungs, the mean CFU/g was
3.5 L-AmB, 4.5 Vori, 5.0 L-AmB + Vori, 5.5 D5W, although there
was no significant difference amongst the groups. At this same time-
point, the mean drug level in the lungs of mice given L-AmB was
6.9 lg/g with no detectable Vori in the lungs of Vori-treated mice.
BAL cytokine levels of IL-1a, IL-1B and IL-22 were significantly
lower for Vori alone vs D5W (p  0.04) but similar for Vori and L-
AmB. In the lungs, IL-22 levels in mice given Vori alone were signifi-
cantly lower than either D5W or L-AmB (p = 0.03). All BUN samples
were within normal limits.
Conclusions Based on the endpoints of early reduction of fungal
burden and long-term survival, L-AmB was more effective than Vori
or L-AmB + Vori for treating murine pulmonary A. flavus infection.
Although all animals survived to d+21 following L-AmB or L-AmB +
Vori treatment, there was some suggestion of initial antagonism
between the two agents based on fungal burden.

Abstract Number: p383

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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