Activity Of Antifungals And Their Combinations Against Aspergillus fumigatus and Aspergillus terreus By Isothermal Microcalorimetry

Ref ID: 18670

Author:

U. Furustrand Tafin, MSc – PhD student, A. Trampuz, MD – MD;

Author address:

Univ. Hosp., Lausanne, Switzerland.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: Combining two antifungal agents with synergistic activity may improve the treatment outcome of invasive mold infections. We evaluated microcalorimetry, based on measurement of growth-related heat production, for evaluation of antifungal combinations against Aspergillus spp. Methods: A. fumigatus ATCC 204305 and A.terreus ATCC 10690 were used. MIC of amphotericin B (AMB) and voriconazole (VOR), and minimal effective concentration (MEC) of caspofungin (CAS) and anidulafungin (ANI) were determined by microbroth dilution at 48h using Sabouraud dextrose broth. For evaluation of combinations, antifungals alone or in combination were tested at 0.25x, 0.5x and 1x MIC or MEC using an inoculum of 2.5 x 105 conidia/ml. Heat production was measured at 37°C for 48h. Time to heat detection (20µW) was recorded. A synergistic effect was defined as delay of fungal heat-production in the presence of an antifungal combination compared to each antifungal alone. Experiments were performed in duplicate. Results: The MIC for A. fumigatus and A. terreus of AMB was 2 µg/ml and 16 µg/ml, of VOR 0.5 µg/ml. The MEC of CAS was 0.25 µg/ml and 0.5µg/ml, of ANI 0.03 µg/ml. AMB and VOR delayed heat production with a complete inhibition at MIC. CAS and ANI alone did not delay heat production but decreased the peak heat-flow. Time to heat detection of the growth control was 7.0 ± 1.6 h and 12.6 ± 0.4h for A. fumigatus and A. terreus respectively. Table shows the delay of fungal heat-flow (in h) in presence of an antifungal combination compared to growth control. Numbers in brackets denotes difference (in h) in heat detection of combinations compared to AMB or VOR alone. Conclusions: Addition of an echinocandin improved the antifungal activity of AMB and VOR against A.fumigatus, whereas only the addition of CAS resulted in an improved activity of AMB for A.terreus. Microcalorimetry enables a quantitative, real-time and accurate evaluation of antifungal activity in combination at sub-MIC concentrations.

Abstract Number: M-1719

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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