Antiretroviral drugs saquinavir and ritonavir reduce inhibitory concentration values of itraconazole against Histoplasma capsulatum strains in vitro

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• 作者：Raimunda Sâ ; mia Nogueira Brilhante^a ; ^b ; ^{brilhante@ufc.br" class="auth_mail" title="E-mail the corresponding author} ; É ; rica Pacheco Caetano^a ; Giovanna Barbosa Riello^a ; Glaucia Morgana de Melo Guedes^a ; Dé ; bora de Souza Collares Maia Castelo-Branco^a ; ^b ; Maria Auxiliadora Bezerra Fechine^b ; Jonathas Sales de Oliveira^a ; Zoilo Pires de Camargo^e ; Jacó ; Ricarte Lima de Mesquita^f ; André ; Jalles Monteiro^d ; Rossana de Aguiar Cordeiro^a ; ^b ; Marcos Fá ; bio Gadelha Rocha^a ; ^c ; José ; Jú ; lio Costa Sidrim^a ; ^b
• 关键词：Histoplasma capsulatum ; Saquinavir ; Ritonavir ; Itraconazole
• 刊名：The Brazilian Journal of Infectious Diseases
• 出版年：2016
• 出版时间：March-April 2016
• 年：2016
• 卷：20
• 期：2
• 页码：155-159
• 全文大小：521 K

文摘

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 1 μg mL⁻¹ for both phases, and ritonavir presented minimum inhibitory concentrations ranging from 0.0312 to 4 μg mL⁻¹and from 0.0625 to 1 μg mL⁻¹ for filamentous and yeast phase, respectively. Concerning the antifungal itraconazole, the minimum inhibitory concentration values ranged from 0.0019 to 0.125 μg mL⁻¹ and from 0.0039 to 0.0312 μg mL⁻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.