Efficacy of amphotericin B lipid complex in a rabbit model of coccidioidal meningitis.
OBJECTIVE
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.
Capilla
Javier
J
California Institute for Medical Research, San Jose, CA, USA.
Clemons
Karl V
KV
Sobel
Raymond A
RA
Stevens
David A
DA
D000284:Administration, Oral; D000666:Amphotericin B / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001167:Arteritis / Q000473:pathology; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000382:microbiology / Q000473:pathology; D002946:Cisterna Magna / Q000382:microbiology; D003045:Coccidioides; D004338:Drug Combinations; D015725:Fluconazole / Q000008:administration & dosage / Q000627:therapeutic use; D006099:Granuloma / Q000473:pathology; D007275:Injections, Intravenous; D008297:Male; D016921:Meningitis, Fungal / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D010713:Phosphatidylcholines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010715:Phosphatidylglycerols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits; D013116:Spinal Cord / Q000382:microbiology / Q000473:pathology; D016019:Survival Analysis
D000935:Antifungal Agents; D004338:Drug Combinations; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D000666:Amphotericin B; D015725:Fluconazole