Abstract
Previous research has confirmed that Candida spp. incubated with the folic acid pathway inhibitor methotrexate can develop multidrug resistance to azoles. However, it remains unclear whether this phenomenon also occurs with other antifoliate agents. The aim of this study was to assess whether a different antifolate —pemetrexed— can induce resistance to azoles among endogenous yeast strains. For this purpose, 15 strains of Candida and 3 strains of Nakaseomyces were stimulated twice with either methotrexate or pemetrexed. Subsequently, minimum inhibitory concentration for fluconazole for each strain was determined before and after stimulation. Susceptibility to fluconazole increased in 7 strains, decreased in 10 strains and did not change in case of 1 strain after exposure to pemetrexed. After exposure to methotrexate susceptibility to fluconazole increased in 7 strains, decreased in 5 strains and did not change in case of 6 strains. One strain of Candida albicans became resistant to fluconazole after stimulation with either methotrexate or pemetrexed.