Activity of fluconazole, caspofungin, anidulafungin and amphotericin B on planktonic and biofilm Candida determined by microcalorimetry.

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Activity of fluconazole, caspofungin, anidulafungin and amphotericin B on planktonic and biofilm Candida determined by microcalorimetry.

Antimicrob Agents Chemother. 2014 Feb 24;

Authors: Maiolo EM, Furustrand Tafin U, Borens O, Trampuz A

Abstract
We investigated the activity of fluconazole, caspofungin, anidulafungin and amphotericin B against planktonic and biofilm Candida using a highly sensitive assay measuring growth-related heat production (microcalorimetry). C. albicans, C. glabrata, C. krusei and C. parapsilosis were tested and the MIC was determined by the microbroth dilution method. The antifungal activity was determined by isothermal microcalorimetry at 37°C in RPMI-1640. For planktonic Candida, heat flow was measured in presence of antifungal dilutions for 24 h. Candida biofilm was formed on porous glass beads for 24 h, exposed to serial dilution of antifungals for 24 h and heat flow was measured for 48 h. The minimum heat inhibitory concentration (MHIC) was defined as the lowest antifungal concentration reducing the heat-flow peak by ≥50% (≥90% for amphotericin B) at 24 h for planktonic Candida and at 48 h for biofilm Candida. Fluconazole (MIC, 0.25->512 μg/ml) and amphotericin B (MIC, 0.25-1 μg/ml) showed higher MIC values than anidulafungin (MIC, 0.03-0.5 μg/ml) and caspofungin (MIC, ≤0.125-0.5 μg/ml). Against biofilm Candida, fluconazole activity was reduced by >1000-fold compared to planktonic counterparts, whereas echinocandins and amphotericin B mainly preserved their activity. Fluconazole induced growth of planktonic C. krusei at sub-MIC concentrations. At high concentrations of caspofungin (>8 μg/ml), paradoxical growth of planktonic C. albicans and C. glabrata was observed. Microcalorimetry enabled real-time evaluation of antifungal activity against planktonic and biofilm Candida. It can be used in future for evaluation of new antifungals, study of resistant strains and antifungal combinations.

PMID: 24566186 [PubMed - as supplied by publisher]