A new in vitro kinetic model to study the pharmacodynamics of antifungal agents: Comparison of the activity of voriconazole and amphotericin B administered alone and in combination against Candida albicans

A. Lignell, A. Johansson, J. Larsson, O. Cars, E. Löwdin, J. Sjölin

Author address: 

Uppsala, Linköping, SE

Abstract: 

Objectives: It has previously been shown that preexposure of Candida albicans (CA) to fluconazole reduces the fungicidal effect of amphotericin B (AMB). The aim of the present study was to investigate whether a similar inhibitory effect was seen between voriconazole (VOC) and AMB in a new in vitro kinetic model. Methods: To a starting inoculum of 10000 CFU/mL of C. albicans CCUG 32723 (Culture Collection, University of Göteborg, Sweden; MICs VOC: 0.004 mg/L, AMB: 0.25 mg/L) in sterile broth, antifungal drugs (VOC: 5 mg/L, AMB: 2.5 mg/L) were administered and placed at 35 degrees centigrade. Antifungal containing medium was eliminated from the culture vessel and replaced by fresh medium with a peristaltic pump at a flow-rate adjusted to obtain the desired half-life of the drugs. A computer controlled infusion pump compensated for the agent with the longer half-life (VOC: 6 h, AMB: 24 h). Repeated sampling for viable counts was made. A magnetic stirrer ensured homogenous mixing. To verify the kinetics, vancomycin was used to simulate VOC and AMB regimens, respectively, and samples for drugconcentrations were measured on an Abbot Architect ci8200 analyser (Abbot, Sweden). Each regimen was performed in triplicate and at each experiment, there was one unexposed control. Results: The mean half-life when vancomycin were used to simulate one dose of VOC was 6.4 h. The mean half-lives when vancomycin were used to simulate three repeated doses of AMB were 23.5, 27.2 and 21.7 h, respectively. With VOC treatment only, viable counts (mean ± SD) were 4.02 ± 0.09, 4.79 ± 0.20 and 5.41 ± 0.55 log 10 CFU/mL at 3, 24 and 48 h, respectively. After treatment with AMB or AMB + VOC simultaneously, viable count was
2006

abstract No: 

P743

Full conference title: 

16th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 16th (2006)