12-month clinical trial of bioencapsulated terbinafine yielded inconsistent resolution for the treatment of Emydomyces testavorans in the Blanding's turtle (Emydoidea blandingii).

IF 1.6 3区 农林科学 Q2 VETERINARY SCIENCES
David J Minich, Anthony J Cerreta, Alexis Nix, Daniel Thompson, Lilyvette Barajas, Ashley Portala, Dania Gamez, Allison Sacerdote-Velat, Matthew R O'Connor, Jennifer M Reinhart, Sherry Cox, Laura Adamovicz, Karisa N Tang, Matthew C Allender
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引用次数: 0

Abstract

Objective: Evaluate multidose bioencapsulated terbinafine for the treatment of Emydomyces testavorans in naturally infected Blanding's turtles (Emydoidea blandingii) and determine if this protocol resulted in therapeutic drug concentrations.

Methods: Blanding's turtles housed within a quarantine facility were treated with oral terbinafine (30 mg/kg) bioencapsulated within earthworms delivered every 48 hours for 12 months in this experimental study. For all turtles, plasma terbinafine concentrations were quantified, and turtles were routinely tested for of E testavorans through quantitative PCR of combined oral, cloacal, and carapace/plastron swabs.

Results: 13 Blanding's turtles were enrolled, and no turtle consistently tested negative via quantitative PCR for E testavorans after 12 months of treatment. The median plasma terbinafine concentrations at months 3 and 6 (trough concentrations) were 18 ng/mL (11 to 78 ng/mL) and 36 ng/mL (10 to 76 ng/mL), respectively. The median plasma terbinafine concentrations at months 9 and 12 (peak concentrations) were 163 ng/mL (61 to 575 ng/mL) and 100 ng/mL (13 to 247 ng/mL), respectively. Plasma terbinafine concentrations inconsistently measured above the MIC for E testavorans. No correlation was observed between plasma terbinafine concentrations and E testavorans target copy number by quantitative PCR.

Conclusions: Multdose treatment at 30 mg/kg with orally administered, bioencapsulated terbinafine every 48 hours for 12 months failed to achieve molecular resolution of natural E testavorans infection in Blanding's turtles and failed to consistently achieve appropriate plasma concentrations.

Clinical relevance: Emydomyces testavorans is associated with a challenging disease process and is of increasing concern for the health, welfare, and conservation of chelonian species. Further investigation of alternative dosing regimens and/or the use of oral terbinafine as part of multimodal treatment protocols is warranted.

生物包封特比萘芬12个月的临床试验对布兰丁鳖(Emydoidea blandingii)治疗睾丸性乳肿的效果不一致。
目的:评价多剂量生物包封特比萘芬治疗自然感染的白斑龟(Emydoidea blandingii)的睾丸乳肿,并确定该方案是否会导致治疗药物浓度的变化。方法:在本实验研究中,在12个月的时间里,每48小时用蚯蚓包裹口服特比萘芬(30mg /kg)治疗隔离设施内的布兰丁龟。对所有海龟进行了血浆特比萘芬浓度的定量检测,并通过口腔、肛肠和甲壳/板联合拭子的定量PCR常规检测了海龟是否含有睾酮戊酯。结果:13只布兰丁氏龟被纳入研究,经过12个月的治疗,没有一只龟的E testavorans在定量PCR中持续呈阴性。第3个月和第6个月特比萘芬的中位血浆浓度(谷浓度)分别为18 ng/mL (11 ~ 78 ng/mL)和36 ng/mL (10 ~ 76 ng/mL)。第9个月和第12个月特比萘芬的中位血浆浓度(峰值浓度)分别为163 ng/mL (61 ~ 575 ng/mL)和100 ng/mL (13 ~ 247 ng/mL)。血浆特比萘芬浓度在E型睾曲安的MIC以上测量不一致。定量PCR结果显示血浆特比萘芬浓度与睾曲霉靶拷贝数无相关性。结论:以30 mg/kg的剂量,每48小时口服生物包膜特比萘芬,持续12个月,未能实现布兰丁龟天然睾曲霉感染的分子分辨率,也未能持续达到适当的血浆浓度。临床意义:睾丸型乳房肿与一种具有挑战性的疾病过程有关,并且对龟类物种的健康、福利和保护越来越关注。有必要进一步研究替代给药方案和/或使用口服特比萘芬作为多模式治疗方案的一部分。
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来源期刊
CiteScore
1.70
自引率
10.00%
发文量
186
审稿时长
3 months
期刊介绍: The American Journal of Veterinary Research supports the collaborative exchange of information between researchers and clinicians by publishing novel research findings that bridge the gulf between basic research and clinical practice or that help to translate laboratory research and preclinical studies to the development of clinical trials and clinical practice. The journal welcomes submission of high-quality original studies and review articles in a wide range of scientific fields, including anatomy, anesthesiology, animal welfare, behavior, epidemiology, genetics, heredity, infectious disease, molecular biology, oncology, pharmacology, pathogenic mechanisms, physiology, surgery, theriogenology, toxicology, and vaccinology. Species of interest include production animals, companion animals, equids, exotic animals, birds, reptiles, and wild and marine animals. Reports of laboratory animal studies and studies involving the use of animals as experimental models of human diseases are considered only when the study results are of demonstrable benefit to the species used in the research or to another species of veterinary interest. Other fields of interest or animals species are not necessarily excluded from consideration, but such reports must focus on novel research findings. Submitted papers must make an original and substantial contribution to the veterinary medicine knowledge base; preliminary studies are not appropriate.
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