Inhibition and killing of Candida albicans in vitro by five imidazoles in clinical use

Five imidazoles (clotrimazole, econazole, ketoconazole, miconazole, and tioconazole) in clinical use were compared for their ability to inhibit and kill Candida albicans. Eleven isolates were obtained from patients before therapy. By spectrophotometric determination of 50% growth inhibition, all isolates were inhibited at low concentrations, with clotrimazole slightly less active than the other four drugs. By the conventional MIC determination, tioconazole was more active than all of the others (P less than 0.01) except clotrimazole. In killing (minimum fungicidal concentration [MFC] assay), tioconazole was the most active by several analyses. Studies of the kinetics of killing indicated that the drugs studied could kill under conditions used for the MFC determination and that tioconazole and ketoconazole could kill particularly rapidly. If the drug was washed from the cells before subculturing, concentrations above the MFC were required to kill, but tioconazole could produce a lethal lesion in all cells virtually instantaneously. These findings are pertinent to MFC and killing kinetics methodology and to the observation of drug persistence after topical application. The results differ from some previous in vitro comparisons made with different methods. They are relevant to conclusions about drug mechanisms based on their abilities to inhibit and to kill, and they underscore the need to study various assay methods and fungal species.