[The fungicidal activity and paradoxical effect of caspofungin against yeast. Influence of culture medium and incubation time]

Abstract

The effect of culture medium and incubation time on the fungicidal activity of caspofungin and on the frequency of paradoxical effect has been studied in 144 blood culture isolates (42, Candida tropicalis, 32 Candida glabrata, 21 Candida krusei, 20 Candida parapsilosis, 11 Candida guilliermondii, 4 Candida famata, 3 Candida lusitaniae, 3 Blastoschizomyces capitatus, 2 Saccharomyces cerevisiae, 2 Yarrowia lipolytica, 1 Candida inconspicua, 1 Candida lambica, 1 Candida sake y 1 Pichia ohmeri). The media assayed were standard RPMI 1640, Antibiotic Medium #3 (AM#3) and AM#3 with 2% of dextrose (AM#3-G). MIC(2) (>or= 50% growth inhibition) and MIC(0) (100% inhibition) at 24 and 48h and the minimum fungicidal concentration (MFC) were determined. The greatest activity of caspofungin was obtained in AM#3 medium followed by AM#3-G and RPMI. Geometric means (GM) MIC(2) at 24/48 h incubation were 0.06/0.12, 0.1/0.2 and 0.65/0.89 mg/l, respectively. GMMIC(0) was 0.1/0.17 (AM#3), 0.16/0.25 (AM#3-G) and 1.06/1.7 mg/l (RPMI). Caspofungin showed fungicidal activity in the three media (GM-MFC, 0.28, 0.38 and 3 mg/l in AM#3, AM#3-G and RPMI, respectively). The percentage of caspofungin tolerant isolates (MFC >or=8 x MIC(0)) was 8.09% (AM#3), 8.3% (AM#3-G) and 13.9% (RPMI). RPMI was the medium less affected by the incubation time and AM#3 the most affected (93.7 and 78.2% of isolates the MIC(2) increased <or=2 Log from 24 to 48 h incubation, respectively). The frequency of paradoxical effect was species-, isolate- and medium- dependent. It is observed at <or=8 mg/l (RPMI), >or=2 mg/l (AM#3) and >or=4 mg/l (AM#3-G). The highest frequency was obtained in RPMI medium and C. tropicalis species and the lowest frequency for C. krusei y C. glabrata.