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

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 mu g mL(-1) for both phases, and ritonavir presented minimum inhibitory concentrations ranging from 0.0312 to 4 mu g mL(-1) and from 0.0625 to 1 mu g mL(-1) for filamentous and yeast phase, respectively. Concerning the anti fungal itraconazole, the minimum inhibitory concentration values ranged from 0.0019 to 0.125 mu g mL(-1) and from 0.0039 to 0.0312 mu g 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. (C) 2016 Published by Elsevier Editora Ltda.CNPqCAPESUniv Fed Ceara, Postgrad Program Med Microbiol, Specialized Med Mycol Ctr, Fortaleza, CE, BrazilUniv Fed Ceara, Postgrad Program Med Sci, Fortaleza, CE, BrazilUniv Estadual Ceara UECE, Postgrad Program Vet Sci, Fortaleza, CE, BrazilUniv Fed Ceara, Dept Stat & Appl Math, Fortaleza, CE, BrazilUniv Fed Sao Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, Sao Paulo, SP, BrazilHosp Sao Jose, Fortaleza, CE, BrazilUniv Fed Sao Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, Sao Paulo, SP, BrazilCNPq: 303396/2014-8CNPq: 552161/2011-0CAPES: AE1 - 0052-000630100/11Web of Scienc