SORENSEN KN, CALDERON L, HOWELL KJ, IRANI PR, SOBEL RA, CLEMONS KV, PAPPAGIANIS D, WILLIAMS PL, STEVENS DA; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 584 (abstract no. 2010).

Santa Clara Valley Med. Ctr.

A rabbit model of coccidioidal meningitis was used to compare the therapeutic efficacies of terbinafine (TBF) and fluconazole (FCZ). Hydrocortisone acetate-treated NZW rabbits were infected intracisternally with either 2.2 x 10[4] or 6.4 x 10[4] Coccidioides immitis arthroconidia. Oral treatment with PEG-200 B.I.D. (n=8), TBF B.I.D. (n=9; 200 mg/kg/day) or FCZ Q.D. (n=8; 80 mg/kg/day) began on day 5 and continued for 21 days. Mean survival times were 20, 24, and 32 days for PEG, TBF, and FCZ, respectively. All of the FCZ-treated (100%; p=0.003), 56% of the TBF-treated (p=0.4), and 25% of the PEG-treated animals survived the length of the study. Both FCZ and TBF were effective at reducing the incidence of paresis. Only FCZ was effective at reducing most neurological and systemic signs. FCZ treatments resulted in lower CSF protein concentrations and WBC counts, and faster clearing of CSF fungal cultures when compared with PEG-treated controls, but TBF treatments had no effect on these parameters. Neither drug affected CSF glucose levels. Mean serum TBF levels by bioassay were within the range of 3.5 to 6.2 microg/ml at 1, 2, and 4 hr post-dose and 0.35 to 7.0 microg/ml at 14 hr post-dose. No TBF was detected in CSF. Mean FCZ levels (24 to 25.5 hr post-dose) by bioassay were 16.4 to 19.2 and 13.5 to 19.2 microg/ml for serum and CSF, respectively. CFU reduction in the spinal cord and brain was over 100-fold (p=0.0005) in FCZ-treated animals and 2-fold (p Publication Types:

• Meeting Abstracts

Keywords:

• Animals
• Coccidioides
• Coccidioidomycosis
• Disease Models, Animal
• Fluconazole
• Leukocyte Count
• Meningitis, Fungal
• Models, Biological
• Naphthalenes
• Rabbits
• terbinafine

Other ID:

• GWAIDS0009269

UI: 102246767

From Meeting Abstracts