• Tássio Henrique Sousa Silva, Claudiane Vansoski Araújo, Khelvin Myner da Costa Santos, Nathanael Dos Santos Alves, Thayse Haylene Soares Gomes, Andressa Kelly Ferreira E Silva, Nayra Cristina Lira Dos Santos Silva, Evandro César Bezerra Damasceno Júnior, Andressa Maria Aguiar de Carvalho, Maria Gabriela Araújo Mendes, Henrique Barros Caminha, Tatiane Caroline Daboit, Thatiana Bragine Ferreira, Leonardo Eurípedes Andrade-Silva, Mario León Silva-Vergara, Kennio Ferreira-Paim, and Fernanda Machado Fonseca.
• BSc. Biomedic, Department of Biomedicine, Universidade Federal do Piauí, Parnaíba (PI), Brazil.
• Sao Paulo Med J. 2020 Jan 1; 138 (1): 404640-46.

BackgroundStatins are used as cholesterol-lowering drugs and may also have direct antimicrobial effects.ObjectiveTo evaluate synergic interactions between simvastatin and both amphotericin B and fluconazole, against environmental strains of Cryptococcus neoformans isolated from captive birds' droppings.Designand SettingExperimental study conducted at Federal University of Piauí, Parnaíba, in collaboration with Federal University of Triângulo Mineiro, Uberaba, Brazil.MethodsStatin susceptibility tests of Cryptococcus neoformans samples were performed as prescribed in standards. Interactions of simvastatin with amphotericin and fluconazole were evaluated using the checkerboard microdilution method. Presence of these interactions was quantitatively detected through determining the fractional inhibitory concentration index (FICI).ResultsIsolates of Cryptococcus neoformans were obtained from 30 of the 206 samples of dry bird excreta (14.5%) that were collected from pet shops and houses. Ten isolates were selected for susceptibility tests. All of them were susceptible to amphotericin and fluconazole. All presented minimum inhibitory concentration (MIC) > 128 µg/ml and, thus, were resistant in vitro to simvastatin. An in vitro synergic effect was shown through combined testing of amphotericin B and simvastatin, such that six isolates (60%) presented FICI < 0.500. Two isolates showed considerable reductions in MIC, from 1 µg/ml to 0.250 µg/ml. No synergic effect was observed through combining fluconazole and simvastatin.ConclusionThese results demonstrate that simvastatin should be considered to be a therapeutic alternative, capable of potentiating the action of amphotericin B. However, further studies are necessary to clarify the real effect of simvastatin as an antifungal agent.

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