One Health Research Group, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Australia.
Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Australia.
Med Mycol. 2019 Feb 1;57(2):204-214. doi: 10.1093/mmy/myy010.
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.
圈养和野生两栖动物受到致命真菌病原体蛙壶菌（Batrachochytrium dendrobatidis，Bd）的灭绝威胁。宠物主人用抗真菌药物特比萘芬（TBF）治疗 Bd 感染的青蛙；然而，由于兽医临床试验有限，它在学术或动物学机构中并未广泛使用。为了评估 TBF 的疗效，我们进行了治疗试验和药代动力学研究，以研究药物在青蛙皮肤中的吸收和持久性；然后将这些数据与针对 Bd 的最小致死浓度（MLC）相关联。尽管最初减少了游动孢子的负荷，但推荐的治疗方案（每天五次，每次 5 分钟，浓度为 0.01%的 TBF 浴）未能治愈实验感染的高山树蛙和自然感染的普通东部蛙。体内外药代动力学研究表明，吸收的 TBF 在暴露增加时会在青蛙皮肤中积累，表明其适合通过直接应用来治疗皮肤病原体。TBF 对游动孢子的 MLC 为 2 小时 100 μg/ml，最小抑菌浓度为 2 μg/ml，这表明在 5 分钟治疗期间吸收的药物浓度不足以治愈高 Bd 负担。每天进行五次 30 分钟的浴疗，Bd 的清除率从 12.5%提高到 50%。更高剂量的 0.02%TBF 使 78%的动物得到治愈；然而，由于 TBF 在皮肤中的半衰期小于 2 小时，持久性较低，并非所有个体都达到了清除效果。因此，在优化方案之前，例如增加暴露频率，目前不建议将 TBF 方案作为治疗 Bd 的通用方法。
