Antifungal activity of four tetracycline analogues against Candida albicans in vitro: potentiation by amphotericin B.
The antifungal activities of four tetracycline analogues in combination with amphotericin B (AmB) were determined against 20 strains of Candida albicans. When a microtiter checkerboard technique was used, minocycline (less than or equal to 10 microgram/ml) acted synergistically with AmB against all strains, whereas doxycycline had a reduced effect, and demeclocycline and tetracycline had no potentiating effect at this concentration. Killing-curve experiments with two strains of C. albicans demonstrated that the combination of minocycline and AmB produced a decrease in number of colony-forming units (cfu) of greater than 2 logs in 4 hr and a 4-log decrease in cfu in 24 hr at concentrations (minocycline, 0.64 microgram/ml; AmB, 0.1 microgram/ml) that were subinhibitory when each agent was used alone and that are readily achieved in human serum and body fluids with conventional doses. The killing-curve technique indicated that doxycycline had an intermediate degree of synergistic activity, whereas tetracycline had no synergistic activity at clinically relevant concentrations.
D000666:Amphotericin B / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D003707:Demeclocycline / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology*; D004357:Drug Synergism; D008911:Minocycline / Q000494:pharmacology*; D013752:Tetracycline / Q000494:pharmacology*; D013754:Tetracyclines / Q000494:pharmacology*
D013754:Tetracyclines; D003707:Demeclocycline; D000666:Amphotericin B; D013752:Tetracycline; D008911:Minocycline; D004318:Doxycycline