In vitro interaction of fluconazole and amphotericin B administered sequentially against Candida albicans: Effect of concentration and exposure time

This study investigated the potential antagonism of fluconazole on amphoter icin B activity against Candida albicans when administered sequentially in vitro. Yeast cells were exposed to fluconazole for time periods ranging fro m 0 to 24 h before the addition of amphotericin B. The combination showed f ungicidal (greater than or equal to 3 log(10) reduction in CFU/mL) activity . After 4 h of exposure to fluconazole, amphotericin B activity was partial ly inhibited at the lower concentration tested (0.25 x MIG). Amphotericin B activity was dramatically decreased by previous exposure to fluconazole fo r greater than or equal to 8 h at both the high and low concentrations test ed. The activity of amphotericin B against yeast exposed to fluconazole far at least 8 Il was indistinguishable from fluconazole alone and was fungist atic (less than or equal to 2 log(10) reduction in CFU/mL). This inhibition of amphotericin B activity persisted for a very shout period (<6 h) after removal of fluconazole from the culture me medium, indicating the need for continued exposure to fluconazole for lasting inhibition of amphotericin B activity. (C) 1998 Elsevier Science Inc.