Apr 29, 2002 - week after the cessation of therapy, all survivors were euthanatized, the ... administered AmBi is superior to oral FLC or intravenous AMB and.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Aug. 2002, p. 2420–2426 0066-4804/02/$04.00⫹0 DOI: 10.1128/AAC.46.8.2420–2426.2002 Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Vol. 46, No. 8
Efficacy of Intravenous Liposomal Amphotericin B (AmBisome) against Coccidioidal Meningitis in Rabbits Karl V. Clemons,1,2,3* Raymond A. Sobel,4,5 Paul L. Williams,6 Demosthenes Pappagianis,7 and David A. Stevens1,2,3 Department of Medicine, Division of Infectious Diseases, Santa Clara Valley Medical Center,1 and California Institute for Medical Research,2 San Jose, California 95128; Department of Medicine, Division of Infectious Diseases and Geographic Medicine,3 and Department of Pathology,4 Stanford University, Stanford, California 94305; Palo Alto Veterans Affairs Health Care System, Palo Alto, California 943045; Kaweah Delta District Hospital, Visalia, California 932916; and Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California 956167 Received 29 April 2002/Accepted 1 May 2002
The efficacy of intravenously administered liposomal amphotericin B (AmBisome [AmBi]) for the treatment of experimental coccidioidal meningitis was compared with those of oral fluconazole (FLC) and intravenously administered conventional amphotericin B (AMB). Male New Zealand White rabbits were infected by intracisternal inoculation of arthroconidia of Coccidioides immitis. Starting 5 days postinfection, animals received one of the following: 5% dextrose water diluent; AMB given at 1 mg/kg of body weight; AmBi given at 7.5, 15, or 22.5 mg/kg intravenously three times per week for 3 weeks; or oral FLC given at 80 mg/kg for 19 days. One week after the cessation of therapy, all survivors were euthanatized, the numbers of CFU remaining in the spinal cord and brain were determined, and histological analyses were performed. All AmBi-, FLC-, or AMB-treated animals survived and had prolonged lengths of survival compared with those for the controls (P < 0.0001). Treated groups had significantly lower numbers of white blood cells and significantly lower protein concentrations in the cerebrospinal fluid compared with those for the controls (P < 0.01 to 0.0005) and had fewer clinical signs of infection (e.g., weight loss, elevated temperature, and neurological abnormalities including motor abnormalities). The mean histological scores for AmBi-treated rabbits were lower than those for FLC-treated and control rabbits (P < 0.016 and 0.0005, respectively); the scores for AMB-treated animals were lower than those for the controls (P < 0.0005) but were similar to those for FLC-treated rabbits. All regimens reduced the numbers of CFU in the brain and spinal cord compared with those for the controls (P
