Activity of Amphotericin B, Azoles and Echinocandins against Aspergillus Species by Isothermal Microcalorimetry

Ref ID: 18649

Author:

U. Furustrand – PhD student, P. Hauser – PhD MER, J. Bille – Professor, A. Trampuz – MD;

Author address:

Univ. Hosp. Lausanne, Lausanne, Switzerland.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: Aspergillus fumigatus is the main agent causing invasive aspergillosis. The prevalence of non-fumigatus and azole-resistant Aspergillus species is rising. Therefore, antifungal susceptibility testing is crucial for guidance of efficient therapy. We evaluated a new method for real-time susceptibility testing of molds based on their of growth-related heat production.
Methods: Five references and six clinical isolates of Aspergillus species were studied. Susceptibility to amphotericin B (AMB), voriconazole (VRC), posaconazole (POS) and caspofungin (CAS) was determined by microbroth dilution (mbd) and microcalorimetry using inoculation with ~104 conidia/ml. Microcalorimetry was performed at 37°C using Sabouraud dextrose broth (SDB) for evaluation of growth characteristics. Detection time was defined as heat flow exceeding 10 μW. For susceptibility testing, serial dilutions of antifungals were added to SDB. The minimal heat inhibitory concentration (MHIC) was defined as the lowest concentration inhibiting 50 % of the cumulative heat of the growth control at 48 h (at 24 h for CAS). Results: The median detection time (range) was 4.1 h (2.1-15.4 h). Amphotericin B and azoles delayed the heat production in a concentration-dependent manner, whereas CAS modified the heat profile. Table shows the MIC (minimum effective concentration [MEC] for CAS) and MHIC for representative isolates. Conclusions: Susceptibility testing results obtained with microcalorimetry correlated with conventional MIC values. In addition, calorimetric data allowed real-time evaluation of different mechanisms of action of tested antifungals. Microcalorimetry offers a new approach for susceptibility testing of Aspergillus species and may be used for investigation of new antifungals and their combinations.

Abstract Number: M-1535

Conference Year: 2012

Link to conference website: NULL

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