Evaluation of amphotericin B and flucytosine in combination against Candida albicans and Cryptococcus neoformans using time-kill methodology.
In this study, time-kill methods were used to evaluate the antifungal activity of amphotericin B and flucytosine, alone and in combination, against six isolates of Candida albicans and Cryptococcus neoformans. Five regimens were tested against each isolate: (1) flucytosine, (2) low-dose amphotericin B, (3) high-dose amphotericin B, (4) low-dose amphotericin B plus flucytosine, and (5) high-dose amphotericin B plus flucytosine. Low-dose amphotericin B and flucytosine, administered alone and simultaneously, demonstrated fungistatic activity against all sample isolates except C. albicans 90028, in which fungicidal activity was detected with the combination. High-dose amphotericin B, alone and in combination, resulted in a rapid fungicidal effect in all isolates. In both the low and high-dose combinations, indifferent activity was demonstrated against all tested isolates. By virtue of the absence of an antagonistic interaction between these two agents, complementary pharmacokinetic profiles, and non-overlapping toxicities, continued clinical use of these agents in combination may be considered.
Keele
D J
DJ
University of Iowa College of Pharmacy, Iowa City, Iowa, USA.
DeLallo
V C
VC
Lewis
R E
RE
Ernst
E J
EJ
Klepser
M E
ME
D000666:Amphotericin B / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D003455:Cryptococcus neoformans / Q000187:drug effects*; D004357:Drug Synergism; D005437:Flucytosine / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000666:Amphotericin B; D005437:Flucytosine