A comparison of dynamic characteristics of fluconazole, itraconazole, and amphotericin B against Cryptococcus neoformans using time-kill methodology

作者: David S. Burgess , Rhonda W. Hastings

DOI: 10.1016/S0732-8893(00)00173-5

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摘要: Abstract This study evaluated the in vitro pharmacodynamics of fluconazole, itraconazole, and amphotericin B against Cryptococcus neoformans . MICs were determined for three clinical isolates according to NCCLS guidelines (M27). Time-kill studies performed using antifungal concentrations 0.25-32xMIC inocula 10 3 5 CFU/ml. At predetermined time points over 72 hours, samples each inoculum/drug combination withdrawn plated a spiral plater. Colony counts after incubation at 35°C 48 hours. Area under kill curves (AUKCs) plotted versus AUC/MIC ratios. Inoculum effect was by calculating an estimated AUKC low inoculum then comparing it measured unpaired Student's t-test. The fluconazole itraconazole isolate 97-1199, 97-1061, 97-585 2, 4, 32μg/ml 0.03, 0.06, 0.5μg/ml, respectively. For B, MIC 0.25μg/ml isolate. triazoles demonstrated fungistatic activity both with exception C. 97-585. Maximal suppression noted 8-16xMIC correlating 192 inocula. Conversely, fungicidal displayed concentration-dependent killing observed >4xMIC >8xMIC high No statistically significant differences detected between AUKCs agent. In conclusion, our results suggest that most effective when maintained 8-16xMIC. Amphotericin on other hand, concentration-dependent; thus, greater exerted higher concentrations.

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