Comparative efficacies of terbinafine and fluconazole in treatment of experimental coccidioidal meningitis in a rabbit model.

A rabbit model of coccidioidal meningitis was used to compare the therapeutic efficacies of terbinafine (TBF) and fluconazole (FCZ). Hydrocortisone acetate-treated New Zealand White male rabbits were infected intracisternally with either 2.2 x 10(4) or 6.4 x 10(4) Coccidioides immitis arthroconidia. Oral treatment with polyethylene glycol 200 (PEG) twice daily (n = 8), TBF twice daily (n = 9; 200 mg/kg of body weight/day), or FCZ once daily (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 rabbits treated with PEG, TBF, and FCZ, respectively. All of the FCZ-treated animals (100%; P = 0.003), 56% of the TBF-treated animals (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 cerebrospinal fluid (CSF) protein concentrations and leukocyte counts and faster clearing of CSF fungal cultures compared with those for PEG-treated controls, but TBF treatments had no significant 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 microgram/ml at 1, 2, and 4 h postdosing and 0.35 to 7.0 microgram/ml at 14 h postdosing. No TBF was detected in CSF. Mean FCZ levels (24 to 25.5 h postdosing) by bioassay were 16.4 to 19.2 and 13.5 to 19.2 microgram/ml in serum and CSF, respectively. The reduction in the numbers of CFU in the spinal cord and brain was over 100-fold (P = 0.0005) in FCZ-treated animals and 2-fold (P

Efficacy of syringomycin E in a murine model of vaginal candidiasis.

Syringomycin E (SR-E), a new antifungal produced by the bacterium Pseudomonas syringae pv. syringae, was evaluated in a murine vaginal candidiasis model. In one study, mice were treated intravaginally b.i.d. for 4 days with drug carrier, SR-E 2% in either PEG-400 or PEG-ointment, or 1% clotrimazole as a positive control. Quantitative vaginal cultures were taken prior to treatment on day 1 and on days 5, 6, and 7. Both formulations showed a reduction of yeast colonization in the vaginas on day 5 (P< or =0.06 and P< or =0.03 for SR-E/PEG-400 and SR-E/PEG ointment, respectively) and SR-E/PEG ointment reduced the colonization on day 7 (P< or =0.06) when compared to carrier treated controls. In a second study, SR-E was formulated in Aquaphor at three higher concentrations of SR-E [3%, 6%, or 12% (w/v)]. SR-E showed dose-dependent efficacy. The 3% dose showed no effect while the 6% and 12% doses reduced the number of yeasts. The 12% dose showed a significant reduction on days 5 (P< or =0.01), 6 (P< or =0.06), and 7 (P< or =0.03) when compared with the drug carrier controls and on day 5 was more effective than clotrimazole (P< or =0.03). Clotrimazole did not significantly reduce the yeasts in the vagina until days 6 (P< or =0.01) and 7 (P< or =0.01) when compared to the drug carrier controls. No vaginal inflammatory response was evident by histological examination in uninfected animals treated with SR-E. No SR-E could be detected in plasma, kidney, or liver. SR-E (12%) was an effective treatment when compared to 1% clotrimazole.