title: Efficacy of high doses of liposomal amphotericin B in the treatment of experimental aspergillosis.
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, 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.
authors: Infectious Diseases Research Laboratory, Infectious Diseases Division, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: María Teresa
authors: MT
authors: Martín
authors: Joan
authors: J
authors: Gavaldà
authors: Pedro
authors: P
authors: López
authors: Xavier
authors: X
authors: Gomis
authors: José Luís
authors: JL
authors: Ramírez
authors: Dolors
authors: D
authors: Rodríguez
authors: Oscar
authors: O
authors: Len
authors: Queralt
authors: Q
authors: Jordano
authors: Isabel
authors: I
authors: Ruiz
authors: Marta
authors: M
authors: Rosal
authors: Benito
authors: B
authors: Almirante
authors: Albert
authors: A
authors: Pahissa
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D008081:Liposomes; D013256:Steroids; D000666:Amphotericin B