Pharmacodynamics of anidulafungin against six Candida species

Pemán, J.

Author address: 

Hospital Universitario La Fe, VALENCIA, Spain

Abstract: 

Background and Objectives: Anidulafungin is a new echinocandin active against both yeasts and filamentous fungi. Unlike other echinocandins, such as caspofungin and micafungin, it is not metabolized in the liver but is eliminated by slow chemical degradation. The aim of this study was to determine the pharmacodynamics of anidulafungin against six Candida species. Material and Methods: One strain each of C. albicans, C. parapsilosis, C. tropicalis, C. glabrata, C. krusei and C. guilliermondii were tested. MICs were determined following the CLSI reference method (Document M27-A2) and were read at 24h. Time killing studies were performed in standard RPMI medium (5 mL), inoculum size 1- 4x 105 CFU/mL . Concentrations tested ranged from 0.03 to 16 mg/L. Aliquots were removed to determine CFU at time 0, 2, 4, 6, 24 and 48h. Time-killing data were fitted to a lineal equation (LogNt = logN0 + kt, where Nt=CFU, t=time, K=killing rate) to determine the time (hours) to achieve 50, 90, 99, and 99.9% of growth reductions from the starting inoculum at each concentration. All time-killing curve studies were conducted in duplicate and on two separate days. Results: The MICs of anidulafungin were 8804;0.03 mg/L for C. albicans, C. tropicalis and C. glabrata; 0.06 mg/L for C. krusei; 0.25 mg/L for C. guilliermondii and 0.5 mg/L for C. parapsilosis. The killing rate increased with concentration and time and was species specific. The time required to reach the fungicidal endpoint (99.9% killing) at 2 mg/L was >48 hours for C. albicans, C. parapsilosis and C. guilliermondii; 3.01 hours for C. glabrata and 13 hours for C. tropicalis. The highest killing rate achieved at all concentrations assayed was for C. glabrata. A decrease in killing at 8 mg/L (paradoxical effect) was observed for C. albicans. Conclusions: Anidulafungin is less active against C. parapsilosis and C. guilliermondii as demonstrated both by MICs and time-killing studies. For some species the fungicidal endpoint is not reached.
2007

abstract No: 

P016

Full conference title: 

3rd Trends in Medical Mycology
    • TIMM 3rd (2011)