Jose A. Vazquez, Dwayne Baxa, Merideth Wierman, Karam Obeid, Dora Vager and Elias Manavathu
Candida glabrata is the second most commonly isolated yeast recovered from blood cultures in the United States. We characterized 85 C. glabrata clinical isolates recovered from various clinical specimens obtained from immunocompromised individuals. This collection was unique because it included a series of isolates recovered from the blood of a patient who only partially responded to antifungal therapy. In vitro activity of caspofungin, micafungin, anidulafungin, fluconazole, voriconazole and amphotericin B was evaluated. Most of the isolates were susceptible to the echinocandins, triazoles and amphotericin B. The geometric mean MIC of the antifungals for the susceptible isolates (n=79) were as follows: caspofungin, 0.061315 ± 0.076934; micafungin, 0.123521 ± 0.457202; anidulafungin, 0.044158 ± 0.895249; fluconazole, 7.013461 ± 20.56794; voriconazole, 0.324939 ± 1.051247; amphotericin B, 0.474923 ± 0.162994. Five of the six serial blood isolates showed a reduced echinocandin susceptibility (RES) to the echinocandins and the triazoles. Characterization of the hot spot 1 region of FKS1, FKS2 and FKS3 showed no amino acid alterations. However, the genes coding for the drug efflux proteins CgCDR1, CgCDR2, CgSNQ2, as well as Cgcyp51 were over-expressed in the isolates with RES and azole resistance compared to the susceptible isolates, indicating that the upregulation of the synthesis of efflux proteins and the drug target is responsible for conferring resistance to triazoles in these isolates. These results demonstrate that multiechinocandin and multi-azole resistant C. glabrata clinical isolates can emerge under the selection pressure imposed by specific drug therapy over a relatively short period of time.