Laboratory of Clinical Research on Dermatozoonoses in Domestic Animals, Evandro Chagas National Institute of Infectious Diseases, Rio de Janeiro, Brazil.
Laboratory of Fungal Cell Biology, Carlos Chagas Filho Institute of Biophysics, Rio de Janeiro, Brazil.
Microbiol Spectr. 2024 Jun 4;12(6):e0396723. doi: 10.1128/spectrum.03967-23. Epub 2024 Apr 22.
Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against sp., both and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-'-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by . In a clinical study, the effect of D13 was then tested in combination with itraconazole (ITC), with or without potassium iodide, in 10 cats with sporotrichosis refractory to the treatment of standard of care with ITC. Improvement or total clinical cure was achieved in five cases after 12 weeks of treatment. Minimal abnormal laboratory findings, e.g., elevation of alanine aminotransferase, were observed in four cats during the combination treatment and returned to normal level within a week after the treatment was ended. Although highly encouraging, a larger and randomized controlled study is required to evaluate the effectiveness and the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis.
This paper reports the first veterinary clinical study of an acylhydrazone anti-fungal (D13) combined with itraconazole against a dimorphic fungal infection, sporotrichosis, which is highly endemic in South America in animals and humans. Overall, the results show that the combination treatment was efficacious in ~50% of the infected animals. In addition, D13 was well tolerated during the course of the study. Thus, these results warrant the continuation of the research and development of this new class of anti-fungals.
酰腙 (AH) 衍生物代表了一类新型抗真菌药物，对 sp. 具有很强的活性，无论是在体外还是在孢子丝菌病的小鼠模型中。在这项研究中，我们证明了 AH 衍生物 D13（4-溴-‘-（3,5-二溴-2-羟基苯亚甲基）-苯甲酰肼）对浮游细胞和 形成的生物膜都有抗真菌功效。在一项临床研究中，然后测试了 D13 与伊曲康唑（ITC）联合使用，是否联合碘化钾，对 10 只对标准护理伊曲康唑治疗有抗性的孢子丝菌病猫进行治疗。在 12 周的治疗后，有 5 例病情改善或完全临床治愈。在联合治疗期间，有 4 只猫仅观察到轻微的异常实验室发现，例如丙氨酸氨基转移酶升高，在治疗结束后一周内恢复正常水平。虽然令人鼓舞，但需要进行更大规模的随机对照研究，以评估使用伊曲康唑和 D13 治疗猫孢子丝菌病的这种新的令人兴奋的药物组合的有效性和安全性。
本文报告了首例兽医临床研究，即用酰腙抗真菌药物（D13）联合伊曲康唑治疗二相真菌感染孢子丝菌病，这种疾病在南美的动物和人类中高度流行。总体而言，结果表明，联合治疗在约 50%的感染动物中有效。此外，在研究过程中，D13 耐受性良好。因此，这些结果证明需要继续研究和开发这种新型抗真菌药物。
