Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Hospital General de México Dr Eduardo Liceaga, Mexico City, Mexico.
Mycoses. 2022 Jun;65(6):650-655. doi: 10.1111/myc.13442. Epub 2022 May 6.
Eumycetoma is a subcutaneous mutilating disease that can be caused by many different fungi. Current treatment consists of prolonged itraconazole administration in combination with surgery. In many centres, due to their slow growth rate, the treatment for eumycetoma is often started before the causative agent is identified. This harbours the risk that the causative fungus is not susceptible to the given empirical therapy. In the open-source drug program MycetOS, ravuconazole and luliconazole were promising antifungal agents that were able to inhibit the growth of Madurella mycetomatis, the most common causative agent of mycetoma. However, it is currently not known whether these drugs inhibit the growth of other eumycetoma causative agents.
Here, we determined the in vitro activity of luliconazole, lanoconazole and ravuconazole against commonly encountered eumycetoma causative agents. MICs were determined for lanoconazole, luliconazole and ravuconazole against 37 fungal isolates which included Madurella species, Falciformispora senegalensis, Medicopsis romeroi and Trematosphaeria grisea and compared to those of itraconazole.
Ravuconazole, luliconazole and lanoconazole showed high activity against all eumycetoma causative agents tested with median minimal inhibitory concentrations (MICs) ranging from 0.008-2 µg/ml, 0.001-0.064 µg/ml and 0.001-0.064 µg/ml, respectively. Even Ma. fahalii and Me. romeroi, which are not inhibited in growth by itraconazole at a concentration of 4 µg/ml, were inhibited by these azoles.
The commonly encountered eumycetoma causative agents are inhibited by lanoconazole, luliconazole and ravuconazole. These drugs are promising candidates for further evaluation as potential treatment for eumycetoma.
外生性真菌病是一种可由多种不同真菌引起的皮下破坏性疾病。目前的治疗方法是长期联合应用伊曲康唑和手术。在许多中心,由于其生长缓慢,在确定病原体之前,通常会开始针对外生性真菌病进行治疗。这存在病原体对经验性治疗药物不敏感的风险。在开源药物项目 MycetOS 中,拉夫康唑和卢立康唑是有前途的抗真菌药物,能够抑制足放线菌病的生长,这是真菌病最常见的病原体。然而,目前尚不清楚这些药物是否能抑制其他外生性真菌病病原体的生长。
在这里,我们确定了卢立康唑、拉夫康唑和兰尼康唑对常见外生性真菌病病原体的体外活性。我们测定了 37 株真菌分离株(包括马杜拉菌属、塞内加尔镰孢霉、罗梅罗美拟青霉和灰绿弯孢霉)对兰尼康唑、卢立康唑和拉夫康唑的 MIC,并与伊曲康唑的 MIC 进行了比较。
拉夫康唑、卢立康唑和兰尼康唑对所有测试的外生性真菌病病原体均显示出高度活性,其最小抑菌浓度(MIC)中位数范围分别为 0.008-2μg/ml、0.001-0.064μg/ml 和 0.001-0.064μg/ml。即使是在 4μg/ml 浓度下伊曲康唑不能抑制生长的 Ma. falhlii 和 Me. romeroi,也被这些唑类药物所抑制。
常见的外生性真菌病病原体被兰尼康唑、卢立康唑和拉夫康唑抑制。这些药物是进一步评估作为外生性真菌病潜在治疗药物的有前途的候选药物。