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


CONCLUSIONS
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.
Martín
María Teresa
MT
Infectious Diseases Research Laboratory, Infectious Diseases Division, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Gavaldà
Joan
J
López
Pedro
P
Gomis
Xavier
X
Ramírez
José Luís
JL
Rodríguez
Dolors
D
Len
Oscar
O
Jordano
Queralt
Q
Ruiz
Isabel
I
Rosal
Marta
M
Almirante
Benito
B
Pahissa
Albert
A
D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008081:Liposomes; D008168:Lung / Q000473:pathology; D009929:Organ Size / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013256:Steroids / Q000494:pharmacology
D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D008081:Liposomes; D013256:Steroids; D000666:Amphotericin B