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JAC Advance Access published online on July 23, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm264
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Efficacy of amphotericin B lipid complex in a rabbit model of coccidioidal meningitis

Javier Capilla1,2,3, Karl V. Clemons1,2,3,*, Raymond A. Sobel4,5 and David A. Stevens1,2,3

1 California Institute for Medical Research, San Jose, CA, USA 2 Department of Medicine, Division of Infectious Diseases, Santa Clara Valley Medical Center, San Jose, CA, USA 3 Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA 4 Department of Pathology, Stanford University, Stanford, CA, USA 5 Veterans Affairs Medical Center, Palo Alto, CA, USA

Received 20 February 2007; returned 18 June 2007; accepted 22 June 2007

* Correspondence address. Division of Infectious Diseases, Santa Clara Valley Medical Center, 751 South Bascom Avenue, San Jose, CA 95128-2699, USA. Tel: +1-408-998-4557; Fax: +1-408-998-2723; E-mail: clemons{at}cimr.org

Objectives: We compared the efficacy of treatments in a rabbit model of coccidioidal meningitis (CM).

Methods: Rabbits were infected intracisternally with Coccidioides immitis and treated with intravenous amphotericin B lipid complex (ABLC), deoxycholate amphotericin B (dAMB), oral fluconazole or diluent [sterile 5% dextrose in water (D5W)]. Survival and cfu in brain, spinal cord and CSF were determined and histology studied. Amphotericin B (AMB) concentrations in serum, CSF and tissue were determined by bioassay.

Results: Fluconazole-treated rabbits and controls lost weight and had decreased mobility. All treatments prolonged survival (P = 0.005) and reduced cfu in brain and spinal cord (P ≤ 0.008); ABLC or dAMB significantly reduced cfu in CNS tissues compared with fluconazole (all P ≤ 0.02). ABLC cleared cfu from CSF faster than dAMB or fluconazole. Histologically, 9/9, 7/8 and 0/24 of the D5W, fluconazole and amphotericin groups, respectively, had severe meningitis. Serum AMB was higher after ABLC at 15 mg/kg than after dAMB (P ≤ 0.02).

Conclusions: Intravenous ABLC was efficacious and could be a treatment option for CM.

Key Words: amphotericin B lipid complex , Coccidioides immitis , AMB


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