Pre-exposure of Candida species to cytarabine and daunorubicin does not affect their in vitro antifungal susceptibility and virulence in flies

摘要

We found that the in vitro susceptibility of C. albicans and C. tropicalis (three isolates each) to antifungals (amphotericin B, caspofungin, and fluconazole) and their virulence in a Toll-deficient fly model of invasive candidiasis were not altered by the previous in vitro exposure to cytarabine, daunorubicin or their combination. The year of 2013 marks the 40th anniversary for the highly successful 7 + 3 remission-induction regimen (7 d of continuous cytarabine [Ara-C] and the first 3 d of intravenous daunorubicin [DNR]) in acute myeloid leukemia (AML). However, infections, including candidiasis, are well known toxicities of that regimen. The treatment of candidiasis in cancer and/ or transplant patients is difficult, and frequently is a failure. Although Candida resistance, an emerging problem in the AML population, has been attributed to antifungal selection pressure, an intriguing hypothesis is that antineoplastic themselves could contribute to resistance-encoding mutations, through their DNA damaging action. Doxorubicin, for example, has been reported to induce efflux pump gene expression in Candida albicans and the antineoplastic methotrexate is likely to contribute to reduce amphotericin B activity by increasing the yeast catalase activity. In addition, such subtle muta-genic effects could affect fitness and virulence of the Candida species.