Cotrimoxazole enhances the in vitro susceptibility of Coccidioides posadasii to antifungals

The aim of the present study was to evaluate the effect of cotrimoxazole on the in vitro susceptibility of Coccidioides posadasii strains to antifungals. A total of 18 strains of C. posadasii isolated in Brazil were evaluated in this study. The assays were performed in accordance with the Clinical and Laboratory Standards Institute guidelines and the combinations were tested using the checkerboard method. The minimum inhibitory concentrations were reduced by 11, 2.4, 4.3 and 3.5 times for amphotericin B, itraconazole, fluconazole and voriconazole, respectively. Moreover, it was seen that cotrimoxazole itself inhibited C. posadasii strains in vitro. The impairment of folic acid synthesis may be a potential antifungal target for C. posadasii.Universidade Federal do Ceará Centro Especializado em Micologia MédicaUniversidade Federal do Ceará Programa de Pós-Graduação em Ciências MédicasUniversidade Federal do Ceará Departamento de QuímicaUniversidade Federal do Ceará Departamento de EstatísticaUniversidade Estadual do Ceará Programa de Pós-Graduação em Ciência VeterináriaUniversidade Federal de São Paulo (UNIFESP) Departamento de Microbiologia, Imunologia e ParasitologiaUNIFESP, Depto. de Microbiologia, Imunologia e ParasitologiaSciEL

Synergistic Effect of Antituberculosis Drugs and Azoles In Vitro against Histoplasma capsulatum var. capsulatum▿

This study evaluated in vitro interactions of antituberculosis drugs and triazoles against Histoplasma capsulatum. Nine drug combinations, each including an antituberculosis drug (isoniazid, pyrazinamide, or ethambutol) plus a triazole (itraconazole, fluconazole, or voriconazole), were tested against both growth forms of H. capsulatum. Stronger synergistic interactions were seen in isoniazid or pyrazinamide plus triazoles for the mold form and ethambutol plus voriconazole for the yeast-like form. Further studies should evaluate these combinations in vivo

Terpinen-4-ol, tyrosol, and beta-lapachone as potential antifungals against dimorphic fungi

This study aimed to evaluate the in vitro antifungal activity of terpinen-4-ol, tyrosol, and beta-lapachone against strains of Coccidioides posadasii in filamentous phase (n=22) and Histoplasma capsulatum in both filamentous (n=40) and yeast phases (n=13), using the broth dilution methods as described by the Clinical and Laboratory Standards Institute, to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of these compounds. The mechanisms of action of these compounds were also investigated by analyzing their effect on cell membrane permeability and ergosterol synthesis. The MIC and MFCf these compounds against C. posadasii, mycelial H. capsulatum, and yeast-like H. capsulatum, were in the following ranges: 350-5720 mu g/mL, 20-2860 mu g/mL, and 40-1420 mu g/mL, respectively for terpinen-4-ol250-4000 mu g/mL, 30-2000 mu g/mL, and 10-1000 mu g/mL, respectively, for tyrosoland 0.48-7.8 mu g/mL, 0.25-16 mu g/mL, and 0.125-4 mu g/mL, respectively for p-lapachone. These compounds showed a decrease in MIC when the samples were subjected to osmotic stress, suggesting that the compounds acted on the fungal membrane. All the compounds were able to reduce the ergosterol content of the fungal strains. Finally, tyrosol was able to cause a leakage of intracellular molecules. (C) 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Ceara, Postgrad Program Med Microbiol, Specialized Med Mycol Ctr, Fortaleza, Ceara, BrazilUniv Fed Ceara, Postgrad Program Med Sci, Fortaleza, Ceara, BrazilUniv Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Cellular Biol Div, Sao Paulo, SP, BrazilUniv Fed Ceara, Dept Stat & Appl Math, Fortaleza, Ceara, BrazilChristus Coll Unichristus, Sch Med, Fortaleza, Ceara, BrazilUniv Estadual Ceara, Postgrad Program Vet Sci, Fortaleza, Ceara, BrazilUniversidade Federal de São Paulo (UNIFESP), Department of Microbiology, Immunology and Parasitology, Cellular Biology Division, São Paulo, SP, BrazilCNPq: 303396/2014-8CNPq: 552161/2011-0CAPES: AE1-0052-000630100/11Web of Scienc