Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Vet Parasitol. 2024 Oct;331:110295. doi: 10.1016/j.vetpar.2024.110295. Epub 2024 Aug 27.
Protozoal diarrhea caused by Tritrichomonas foetus (blagburni) is a prevalent, lifelong, and globally distributed burden in domestic cats. Treatment is limited to the use of 5-nitroimidazoles and treatment failure is common. The repurposed gold salt compound auranofin has killing activity against diverse protozoa in vitro but evidence of efficacy in naturally occurring protozoal infections is lacking. This exploratory study investigated the efficacy and safety of auranofin for treatment of cats with naturally occurring, 5-nitroimidazole-resistant, T. foetus infection. The minimum lethal concentration (MLC) of auranofin against 5 isolates of feline T. foetus was determined under aerobic conditions in vitro. Healthy cats and cats with T. foetus infection were treated with immediate release auranofin (range, 0.5-3 mg/cat for 7 days) or guar gum-coated auranofin capsules (0.5 or 3 mg/cat for 7 days). Adverse effects were monitored by clinical signs and clinicopathologic testing. Efficacy was determined by fecal consistency score, bowel movement frequency, and single-tube nested PCR of feces for T. foetus rDNA. Fecal samples were assayed for concentrations of auranofin, known and predicted metabolites of auranofin, gold containing molecules, and total gold content using HPLC, LC-MS, ion mobility-MS, and ICP-MS, respectively. Auranofin was effective at killing isolates of feline T. foetus at MLC ≥ 1 μg/ml. Treatment of cats with T. foetus infection with either immediate release auranofin or a colon-targeted guar gum-coated tablet of auranofin did not eradicate infection. Treatment failure occurred despite fecal concentrations of gold that met or exceeded the equivalent MLC of auranofin. Neither auranofin, known or predicted metabolites of auranofin, nor any gold-containing molecules >100 Da could be detected in fecal samples of treated cats. Adverse effects associated with auranofin treatment were common but minor. These studies identify that in vitro susceptibility test results of auranofin may not translate to treatment effectiveness in vivo even when achieving gold concentrations equivalent to the MLC of auranofin in the target environment. These studies further establish the absence of any predicted or unpredicted gold containing metabolites in feces after oral administration of auranofin.
由胎儿三毛滴虫（blagburni）引起的原生动物腹泻是一种普遍存在的、终身的、全球性分布的家猫负担。治疗仅限于使用 5-硝基咪唑类药物，且治疗失败很常见。再利用的金盐化合物金诺芬对体外多种原生动物具有杀伤活性，但缺乏其自然发生的原生动物感染疗效的证据。这项探索性研究调查了金诺芬治疗自然发生的、5-硝基咪唑类药物耐药的胎儿三毛滴虫感染猫的疗效和安全性。在体外有氧条件下，测定了金诺芬对 5 株猫胎儿三毛滴虫的最小致死浓度（MLC）。健康猫和感染胎儿三毛滴虫的猫分别用即时释放金诺芬（0.5-3mg/猫，持续 7 天）或瓜尔胶包被金诺芬胶囊（0.5 或 3mg/猫，持续 7 天）治疗。通过临床症状和临床病理检测监测不良反应。通过粪便一致性评分、排便频率以及粪便中胎儿三毛滴虫 rDNA 的单管巢式 PCR 来确定疗效。使用 HPLC、LC-MS、离子迁移-MS 和 ICP-MS 分别检测粪便中金诺芬、金诺芬的已知和预测代谢物、含金分子和总金含量。金诺芬在 MLC≥1μg/ml 时能有效杀灭猫胎儿三毛滴虫分离株。用即时释放金诺芬或结肠靶向瓜尔胶包被金诺芬片治疗胎儿三毛滴虫感染的猫并未根除感染。尽管粪便中的金浓度达到或超过金诺芬的 MLC，但治疗失败仍会发生。在接受治疗的猫的粪便样本中，均未检测到金诺芬、金诺芬的已知或预测代谢物或任何 >100Da 的含金分子。与金诺芬治疗相关的不良反应很常见，但很轻微。这些研究表明，即使在目标环境中达到金诺芬 MLC 的金浓度，金诺芬的体外药敏试验结果也可能无法转化为体内治疗效果。这些研究进一步确定，口服金诺芬后粪便中不存在任何预测或未预测的含金代谢物。
