Michael W. Hyatt1, DVM; Timothy A. Georoff2, VMD, DACZM; Donna M. Ialeggio2, DVM; Rebecca L. Wells3, MS, DVM; Craig A. Harms4, DVM, PhD, DACZM; Allison N. Wack5, DVM
Abstract
Aspergillosis is a common respiratory fungal disease in penguins managed under human care.4 Triazole antifungal drugs, such as itraconazole, are most commonly used for treatment;6 however, itraconazole treatment failures from drug resistance are becoming more common, requiring newer treatment options2,7. Voriconazole, a newer triazole, is being used more often. Until recently,8 no voriconazole pharmacokinetic studies have been performed in penguins, leading to empirical dosing based on other avian studies, which has led to increased anecdotal reporting of drug toxicity and even potential death. This report describes 13 cases of voriconazole toxicity in three penguin species: 10 African penguins (Spheniscus demersus), two Humboldt penguins (S. humboldti), and one macaroni penguin (Eudyptes chrysolophus) between four different institutions. Clinical signs of toxicity ranged and progressed in severity from anorexia, lethargy, weakness, ataxia, paraparesis, apparent vision changes, seizure-like activity to generalized seizures. Similar signs of toxicity have also been reported in humans,3,5,10 in whom voriconazole therapeutic range for Aspergillus spp. infections is 2–6 µg/ml1. Plasma voriconazole levels were measured in six penguins, which were markedly elevated at 44.28 and 57.93 µg/ml in more severely affected birds with paraparesis and seizures, respectively; moderately elevated at 15.69 and 17.78 µg/ml in mildly ataxic birds; and mildly elevated at 8.12 and 10.63 µg/ml in anorexic, lethargic and weak birds. These concentrations were well above those known to result in CNS toxicity, including encephalopathy, in humans.9 This report highlights the importance of species-specific dosing of voriconazole and blood therapeutic monitoring, and warrants further investigation and pharmacokinetic studies.
Acknowledgments
The authors wish to thank the husbandry and animal care staff from their respective institutions for their dedicated care of these penguins. We thank Dr. Waldoch from Omaha’s Henry Doorly Zoo and Aquarium for case submissions. Lastly, we thank Mr. Harshaw of Animal Interaction Design Group.
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