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 amphotericin B activity against Candida albicans when administered sequentially in vitro. Yeast cells were exposed to fluconazole for time periods ranging from 0 to 24 h before the addition of amphotericin B. The combination showed fungicidal (> or = 3 log 10 reduction in CFU/mL) activity. After 4 h of exposure to fluconazole, amphotericin B activity was partially inhibited at the lower concentration tested (0.25 x MIC). Amphotericin B activity was dramatically decreased by previous exposure to fluconazole for greater than or equal to 8 h at both the high and low concentrations tested. The activity of amphotericin B against yeast exposed to fluconazole for at least 8 h was indistinguishable from fluconazole alone and was fungistatic (< or = 2 log 10 reduction in CFU/mL). This inhibition of amphotericin B activity persisted for a very short period (< 6 h) after removal of fluconazole from the culture medium, indicating the need for continued exposure to fluconazole for lasting inhibition of amphotericin B activity.
Ernst
E J
EJ
College of Pharmacy, University of Iowa, Iowa City 52242, USA.
Klepser
M E
ME
Pfaller
M A
MA
D000666:Amphotericin B / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015725:Fluconazole / Q000008:administration & dosage / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009172:Mycology / Q000379:methods; D013997:Time Factors
D000935:Antifungal Agents; D000666:Amphotericin B; D015725:Fluconazole