Determination of MICs of antifungal drugs at different growth stages of filamentous fungi

J.Meletiadis, E.A.H.Kramer, J.F.G.M.Meis, J.W.Mouton, P.E.Verweij


Background: MICs of antifungal drugs are elevated during prolonged incubation, which may be related to the different growth phases of fungi. The various growth phases are apparent after different incubation periods in various nutrient media. The MICs of amphotericin B (AB), itraconazole (IT) and terbinafine (TB) against 5 strains of Aspergillus fumigatus, Rhizopus oryzae and Scedosporium prolificans were determined in antibiotic medium 3 (AM3), yeast nitrogen base medium (YNB), liquid Sabouraud (SAB) and RPMI-1640 (RPMI) at various growth phases during the growth of these fungi. Methods: Conidia and spores at a final inoculum of 104 CFU/mL were incubated in two-fold serial dilutions of AB (16-0.015 mg/L), TB and IT (32-0.03 mg/L) in AM3, YNB, SAB and RPMI. MICs were determined during the first transition period, the log-phase, the second transition period and the stationary phase after 14, 20, 24, 48, and 72 h of incubation at 37'baC in 96 flatbottom microtitration plates. The geometric mean of the MICs (GM-MICs) were calculated for each growth phase and nutrient medium, and the differences of second logarithm of the MICs were analysed by ANOVA (repeated measures test). Results: Statistical significant differences between the MICs of antifungal drugs at different growth phases were found in the four nutrient media for all species (P 0.08) and between the MICs after 14, 20, and 24 h of incubation when R. oryzae was tested against AB and IT in all media. Up to 3-fold increase of GM-MICs were observed when the growth control was reached the stationary phase (after 48 h incubation for A. fumigatus and after 24 h for R. oryzae).

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11th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 11th (2001)