Antifungal drug susceptibility profiles and molecular mechanisms of azole resistance in Candida blood stream isolates

Abstract

PurposeThe purpose of this study was to determine the activity of fluconazole, voriconazole, posaconazole, amphotericin B, micafungin and caspofungin against Candida blood stream isolates and to investigate the molecular mechanisms of azole resistance in fluconazole resistant isolates. MethodsThe in vitro susceptibilities of Candida isolates to fluconazole, voriconazole, posaconazole, amphotericin B, micafungin and caspofungin were tested by E-test ERG11, CDR1, CDR2 and MDR1 genes expression of fluconazole resistant, fluconazole (S-DD) and fluconazole intermediate resistant isolates were investigated by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). ResultsC. albicans (41%) was the most frequently isolated fungal species from blood stream infections followed by C. parapsilosis (22%). All C. albicans isolates except one and all C. tropicalis isolates were found to be susceptible to fluconazole. Overall, 21% of C. glabrata isolates were resistant to fluconazole. None of the Candida isolates were found to be resistant to caspofungin except 2 ​C. glabrata isolates. Overexpression of ERG11 and CDR1 genes were detected in all fluconazole S-DD and fluconazole resistant C. glabrata isolates, while CDR2 overexpression was observed in 91% fluconazole S-DD and 67 of % fluconazole resistant C.glabrata isolates. The overexpression of MDR1, ERG11 and CDR1 genes were found 100%, 80% and 80%, respectively, in fluconazole resistant C. parapsilosis isolates. ConclusionMost of the Candida isolates were susceptible to posaconazole and caspofungin. Our data also highlighted that overexpression of efflux pump genes major cause of azole resistance.