Efficacy of voriconazole in Japanese quail (Coturnix japonica) experimentally infected with Aspergillus fumigatus.
Aspergillus fumigatus causes disease in birds. Our objectives were to determine pharmacokinetic parameters and evaluate efficacy of voriconazole (VCZ) in a novel experimental quail model. After a single oral VCZ dose of 20 or 40 mg/kg, plasma concentrations peaked 2 h postdose (5.8 and 6.9 microg/ml) and remained above 0.5 microg/ml for 4 and 12 h postdose, respectively. For the efficacy study, ten-day-old Japanese quail (n = 60) were infected intratracheally with A. fumigatus conidia. Daily oral VCZ at 20 or 40 mg/kg was initiated 24 h postinfection (PI); infected diluent-treated birds were given de-ionized water orally. Preassigned birds were euthanized on days 5 or 10 PI. VCZ at 40 mg/kg prolonged survival compared to 20 mg/kg or diluent-treatment (P < 0.05) and lungs from birds given VCZ at 40 mg/kg had fewer colony forming units (CFU) than diluent-treated (P = 0.03). At day 10 PI, birds treated with VCZ at 20 mg/kg had significantly fewer fungi in the lungs as demonstrated by methenamine silver stain (P = 0.017) or immunohistochemistry, as compared to diluent-treated (P = 0.034). Histopathologically, VCZ-treated birds did not have necrotic lesions and showed a trend toward fewer with acute inflammatory changes. VCZ at 40 mg/kg was efficacious in quail with experimental pulmonary aspergillosis.
Tell
Lisa A
LA
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. latell@ucdavis.edu
Clemons
Karl V
KV
Kline
Yvonne
Y
Woods
Leslie
L
Kass
Philip H
PH
Martinez
Marife
M
Stevens
David A
DA
D000818:Animals; D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects*; D003370:Coturnix / Q000382:microbiology*; D004195:Disease Models, Animal; D005260:Female; D006651:Histocytochemistry; D008168:Lung / Q000473:pathology; D008297:Male; D008826:Microbial Sensitivity Tests; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D014230:Triazoles / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole