Interaction between fluconazole and amphotericin B in mice with systemic infection due to fluconazole-susceptible or -resistant strains of Candida albicans

The interaction between fluconazole (Flu) and amphotericin B (AmB) was eval uated in a murine model of systemic candidiasis for one Flu-susceptible str ain (MIC, 0.5 mu g/ml), two strains with intermediate Flu resistance (Flu m id-resistant strains) (MIC, 64 and 128 mu g/ml), and one highly Flu-resista nt strain (MIC, 512 mu g/ml) of Candida albicans. Differences in fungal den sities in kidneys of infected mice after 24 h of therapy and in survival ra tes at 62 days of mice treated with an antifungal drug or a combination of antifungal drugs for 4 days were compared. For the Flu-susceptible and Flu mid-resistant strains, the combination of Flu and AmB was antagonistic, as shown by both quantitative culture results and survival, The interaction wa s additive for the highly Flu-resistant strain. These results suggest that the combination of Flu and AmB should be used with caution in infections du e to fungi that are usually susceptible to both antifungal agents and as em pirical antifungal drug therapy.