Brilhante Raimunda Sâmia Nogueira, Caetano Érica Pacheco, Riello Giovanna Barbosa, Guedes Glaucia Morgana de Melo, Castelo-Branco Débora de Souza Collares Maia, Fechine Maria Auxiliadora Bezerra, Oliveira Jonathas Sales de, Camargo Zoilo Pires de, Mesquita Jacó Ricarte Lima de, Monteiro André Jalles, Cordeiro Rossana de Aguiar, Rocha Marcos Fábio Gadelha, Sidrim José Júlio Costa
Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil; Postgraduate Program in Medical Sciences, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
Braz J Infect Dis. 2016 Mar-Apr;20(2):155-9. doi: 10.1016/j.bjid.2015.11.003. Epub 2015 Dec 31.
Recent studies have shown that some drugs that are not routinely used to treat fungal infections have antifungal activity, such as protease inhibitor antiretroviral drugs. This study investigated the in vitro susceptibility of Histoplasma capsulatum var. capsulatum to saquinavir and ritonavir, and its combination with the antifungal itraconazole. The susceptibility assay was performed according to Clinical and Laboratory Standards Institute guidelines. All strains were inhibited by the protease inhibitor antiretroviral drugs. Saquinavir showed minimum inhibitory concentrations ranging from 0.125 to 1μgmL(-1) for both phases, and ritonavir presented minimum inhibitory concentrations ranging from 0.0312 to 4μgmL(-1)and from 0.0625 to 1μgmL(-1) for filamentous and yeast phase, respectively. Concerning the antifungal itraconazole, the minimum inhibitory concentration values ranged from 0.0019 to 0.125μgmL(-1) and from 0.0039 to 0.0312μgmL(-1) for the filamentous and yeast phase, respectively. The combination of saquinavir or ritonavir with itraconazole was synergistic against H. capsulatum, with a significant reduction in the minimum inhibitory concentrations of both drugs against the strains (p<0.05). These data show an important in vitro synergy between protease inhibitors and itraconazole against the fungus H. capsulatum.
最近的研究表明，一些并非常规用于治疗真菌感染的药物具有抗真菌活性，比如蛋白酶抑制剂抗逆转录病毒药物。本研究调查了荚膜组织胞浆菌荚膜变种对沙奎那韦和利托那韦的体外敏感性，以及它们与抗真菌药物伊曲康唑联合使用的情况。药敏试验按照临床和实验室标准协会的指南进行。所有菌株均受到蛋白酶抑制剂抗逆转录病毒药物的抑制。沙奎那韦对两个阶段的最小抑菌浓度范围为0.125至1μg/mL（-1），利托那韦对丝状相和酵母相的最小抑菌浓度分别为0.0312至4μg/mL（-1）和0.0625至1μg/mL（-1）。关于抗真菌药物伊曲康唑，丝状相和酵母相的最小抑菌浓度值分别为0.0019至0.125μg/mL（-1）和0.0039至0.0312μg/mL（-1）。沙奎那韦或利托那韦与伊曲康唑联合使用对荚膜组织胞浆菌具有协同作用，两种药物对菌株的最小抑菌浓度均显著降低（p<0.05）。这些数据表明蛋白酶抑制剂与伊曲康唑在体外对荚膜组织胞浆菌具有重要的协同作用。
