The efficacy and pharmacokinetics of terbinafine against the frog-killing fungus (Batrachochytrium dendrobatidis)

Roberts, Alexandra A., Berger, Lee, Robertson, Sherryl G., Webb, Rebecca J., Kosch, Tiffany A., McFadden, Michael, Skerratt, Lee F., Glass, Beverley D., Motti, Cherie A., and Brannelly, Laura A. (2018) The efficacy and pharmacokinetics of terbinafine against the frog-killing fungus (Batrachochytrium dendrobatidis). Medical Mycology. (In Press)

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Abstract

Captive and wild amphibians are under threat of extinction from the deadly fungal pathogen Batrachochytrium dendrobatidis (Bd). The antifungal drug terbinafine (TBF) is used by pet owners to treat Bd-infected frogs; however, it is not widely used in academic or zoological institutions due to limited veterinary clinical trials. To assess TBF’s efficacy, we undertook treatment trials and pharmacokinetic studies to investigate drug absorption and persistence in frog skin; and then we correlated these data to the minimal lethal concentrations (MLC) against Bd. Despite an initial reduction in zoospore load, the recommended treatment (five daily 5 min 0.01% TBF baths) was unable to cure experimentally infected alpine tree frogs and naturally infected common eastern froglets. In vitro and in vivo pharmacokinetics showed that absorbed TBF accumulates in frog skin with increased exposure, indicating its suitability for treating cutaneous pathogens via direct application. The MLC of TBF for zoosporangia was 100 μg/ml for 2 h, while the minimal inhibitory concentration was 2 μg/ml, suggesting that the drug concentration absorbed during 5 min treatments is not sufficient to cure high Bd burdens. With longer treatments of five daily 30 min baths, Bd clearance improved from 12.5% to 50%. A higher dose of 0.02% TBF resulted in 78% of animals cured; however, clearance was not achieved in all individuals due to low TBF skin persistence, as the half-life was less than 2 h. Therefore, the current TBF regime is not recommended as a universal treatment against Bd until protocols are optimized, such as with increased exposure frequency.

Item ID: 53053
Item Type: Article (Research - C1)
ISSN: 1369-3786
Keywords: antifungal; pharmacokinetics; amphibian declines
Funders: Queensland Government (QG), Taronga Conservation Science Initiative, Queensland Department of Environment and Heritage Protection, Australian Research Council (ARC), Taronga Zoo, New South Wales Office of Environment and Heritage, Advance Women's Academic Fund, James Cook University (JCU)
Projects and Grants: QG Accelerate Fellowship 14-208, ARC FT100100375, ARC LP110200240, ARC DP120100811, JCU Collaboration Across Boundaries Grant
Date Deposited: 06 Apr 2018 02:23
FoR Codes: 07 AGRICULTURAL AND VETERINARY SCIENCES > 0707 Veterinary Sciences > 070707 Veterinary Microbiology (excl Virology) @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1115 Pharmacology and Pharmaceutical Sciences > 111501 Basic Pharmacology @ 50%
SEO Codes: 96 ENVIRONMENT > 9604 Control of Pests, Diseases and Exotic Species > 960499 Control of Pests, Diseases and Exotic Species not elsewhere classified @ 100%
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