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

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 <or= 0.008); ABLC or dAMB significantly reduced cfu in CNS tissues compared with fluconazole (all P <or= 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 <or= 0.02).

CONCLUSIONS

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