Background: To estimate its effective blood concentration, the mode of action of MCFG with a high plasma protein binding ratio (99.8%) was tested against Candida albicans in serum. Methods: C. albicans FP633 was used. Volunteers’ serum was inactivated, and buffered with 20 mM Hepes (pH 7.4). Minimal inhibitory concentrations (MICs) in MOPS buffered RPMI1640 medium (pH 7.0) or in serum were determined by micro-dilution and inoculations of 1x104 cells/ml. MICs were read under a microscope after 18 hours incubation at 37ºC and 5% CO2. Simultaneously, multiply obtained serum from an 85-year-old female patient given 2 mg/kg MCFG once a day was diluted twofold with volunteers’ serum, and maximum dilution ratios inhibited the growth of the strain were read as antifungal titers. The disk diffusion method was also used to calculate the patient serum activity. MCFG standards were diluted serial twofold in the medium or serum from 160 to1.25 Âµg/ml, respectively. Results: The MIC of MCFG in serum against C. albicans FP633 was 1 Âµg/ml, which was 8-fold higher than that in the medium (0.125 Âµg/ml). This activity was >50-fold higher than the free MCFG concentration estimated by the plasma protein binding ratio. MICs in serum as estimated by antifungal titers and HPLC-based concentrations ranged from 0.7-0.9 Âµg/ml. The inhibition zones of disks dipped in serum containing >10 Âµg/ml MCFG were smaller than those dipped in the medium. Inversely, the inhibition zones of disks dipped in serum containing 50-fold greater anticandidal activity in serum than the activity predicted by free concentrations. MCFG’s binding to albumin appeared weak and easy to diffuse. Moreover, MCFG was shown to act synergistically with serum against C.albicans.
Full conference title:
46th Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 46th