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 (10 tAg/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 colonyforming units (cfu) of >2 logs in 4 hr and a 4-log decrease in cfu in 24 hr at concentrations (minocycline, 0.64 Mg/ml; AmB, 0.1 Fg/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.