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 1mgmL( 1) for both phases, and ritonavir presented minimum inhibitory concentrations ranging from 0.0312 to 4mgmL( 1)and from 0.0625 to 1mgmL( 1) for filamentous and yeast phase, respectively. Concerning the antifungal itraconazole, the minimum inhibitory concentration values ranged from 0.0019 to 0.125mgmL( 1) and from 0.0039 to 0.0312mgmL( 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.
The Brazilian journal of infectious diseases an official publication of the Brazilian Society of Infectious Diseases