Combined effect of amphotericin B and rifampin on Candida species

Synergism with the combination of rifampin and amphotericin B in vitro has been demonstrated with a limited number of Candida strains. To extend these studies (particularly at clinically achievable levels of rifampin), we evaluated the in vitro combined activity of serial twofold dilutions of amphotericin B (0.1 to 6.0 microgram/ml) against 11 concentrations of rifampin (0.2 to 200 microgram/ml) for 40 strains of Candida: 20 Candida albicans, 7 Candida parapsilosis, 8 Candida tropicalis, 2 Candida stellatoidea, 2 Candida guilliermondii, and 1 Candida krusei by using a modified checkerboard microtitration technique. An additive or synergistic effect was seen for 45% of strains with 6.25 microgram of rifampin per ml added to amphotericin B. Whereas the minimal inhibitory concentration to amphotericin B alone was 0.4 microgram/ml or less for 50% of the strains, the percentage increased to 90 with the addition of 6.25 microgram of rifampin per ml. A similar effect was seen with killing: 25% of the strains were killed by 0.4 microgram or less of amphotericin B alone per ml, and 75% of the strains were killed with the addition of 6.25 microgram of rifampin per ml. In vivo studies are needed for confirmation of the usefulness of combined amphotericin B and rifampin therapy.