Prophylactic administration of liposomal amphotericin B is superior to treatment in a murine model of invasive aspergillosis after hematopoietic cell transplantation.
With use of a novel model of invasive Aspergillus fumigatus, the efficacy of prophylactic versus therapeutic administration of liposomal amphotericin B (L-AmB) was tested in C57BL/6 mice. After lethal irradiation and transplantation of whole bone marrow (d 0), animals were challenged with conidia either intravenously or via nasal instillation on d +3 and divided into 3 groups: group I received 5% dextrose in water throughout the study period; group II received L-AmB, 5 mg/kg, beginning on d +4; and group III received L-AmB, 5 mg/kg on d -4, d -2, d 0, and d +2, then daily starting d +4. Groups I and II did not survive intravenous challenge, whereas group III had a 40% survival rate. After nasal instillation of conidia, the survival was 25%, 35%, and 85% for mice in groups I, II, and III, respectively. These results demonstrate that prophylactic administration of L-AmB increased early survival against lethal challenge with A. fumigatus, compared with therapy instituted after infection.
BitMansour
Andrew
A
Division of Bone Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Brown
Janice M Y
JM
D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D019072:Antibiotic Prophylaxis; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy / Q000517:prevention & control*; D001232:Aspergillus fumigatus; D004195:Disease Models, Animal; D018572:Disease-Free Survival; D018380:Hematopoietic Stem Cell Transplantation; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D011183:Postoperative Complications / Q000517:prevention & control*; D016896:Treatment Outcome
D000935:Antifungal Agents; D008081:Liposomes; C068538:liposomal amphotericin B; D000666:Amphotericin B