Synergic effect of simvastatin in combination with amphotericin B against environmental strains of Cryptococcus neoformans from northeastern Brazil: a prospective experimental study

• Published in: São Paulo medical journal 2020-01, Vol.138 (1), p.40-46
• Main Authors: Silva, Tássio Henrique Sousa, Araújo, Claudiane Vansoski, Santos, Khelvin Myner da Costa, Alves, Nathanael Dos Santos, Gomes, Thayse Haylene Soares, Silva, Andressa Kelly Ferreira E, Silva, Nayra Cristina Lira Dos Santos, Damasceno Júnior, Evandro César Bezerra, Carvalho, Andressa Maria Aguiar de, Mendes, Maria Gabriela Araújo, Caminha, Henrique Barros, Daboit, Tatiane Caroline, Ferreira, Thatiana Bragine, Andrade-Silva, Leonardo Eurípedes, Silva-Vergara, Mario León, Ferreira-Paim, Kennio, Fonseca, Fernanda Machado
• Format: Article
• Language: English
• Subjects: Antifungal agents; Antifungal therapy; Cryptococcosis; Cryptococcosis treatment; Cryptococcus neoformans; Drug interactions; Drug resistance, fungal; Fractional inhibitory concentration index; HIV infection; MEDICINE, GENERAL & INTERNAL; Original
• ISSN: 1516-3180; 1806-9460; 1806-9460
• DOI: 10.1590/1516-3180.2019.0107.R2.16092019

Statins are used as cholesterol-lowering drugs and may also have direct antimicrobial effects. To evaluate synergic interactions between simvastatin and both amphotericin B and fluconazole, against environmental strains of Cryptococcus neoformans isolated from captive birds' droppings. Experimental study conducted at Federal University of Piauí, Parnaíba, in collaboration with Federal University of Triângulo Mineiro, Uberaba, Brazil. Statin 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). Isolates 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. These 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.