title: Efficacy of high loading doses of liposomal amphotericin B in the treatment of experimental invasive pulmonary aspergillosis.
abstract: This study aimed to investigate whether initial treatment of experimental pulmonary aspergillosis with high loading doses can be used as an alternative to standard therapeutic regimens. Steroid-immunosuppressed rats, infected intratracheally with Aspergillus fumigatus, received either amphotericin B deoxycholate (d-AmB) 1 mg/kg/day, liposomal amphotericin B (L-AmB) 5 mg/kg/day, or underwent a 3-day course of L-AmB 10 mg/kg, or 10 mg/kg for the first 3 or 4 days of treatment, followed by 3 mg/kg until the end of treatment. Therapy started 24 h after fungal challenge and lasted for 7 days. Compared to controls, survival was improved significantly in animals receiving any L-AmB regimen (p <or= 0.003), but not d-AmB. Compared with d-AmB, L-AmB at initial doses of 10 mg/kg followed by 3 mg/kg/day was consistently more effective, but only when measured in terms of survival, lung weight and glucosamine levels, and not log CFU. Despite the absence of significant differences between any of the L-AmB regimens, a trend towards better response rates with the higher loading dose was observed.
authors.affiliation: Servei de Malalties Infeccioses, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. jogavalda@vhebron.net
authors.forename: J
authors.initials: J
authors.lastname: Gavaldà
authors.forename: T
authors.initials: T
authors.lastname: Martín
authors.forename: P
authors.initials: P
authors.lastname: López
authors.forename: X
authors.initials: X
authors.lastname: Gomis
authors.forename: J L
authors.initials: JL
authors.lastname: Ramírez
authors.forename: D
authors.initials: D
authors.lastname: Rodríguez
authors.forename: O
authors.initials: O
authors.lastname: Len
authors.forename: Y
authors.initials: Y
authors.lastname: Puigfel
authors.forename: I
authors.initials: I
authors.lastname: Ruiz
authors.forename: A
authors.initials: A
authors.lastname: Pahissa
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016867:Immunocompromised Host; D008172:Lung Diseases, Fungal / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000935:Antifungal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B