Ultrastructural (US) Characterization and Pharmacodynamic Evaluation of Flucytosine (F) and Voriconazole (V) in an In-Vitro Model of Candida Spp. (CS) Infective Endocarditis (IE).

M. P. PAI, M. SAMPLES, C. MULLEN, A. APODACA, N. OKOLI, R. C. MERCIER;

Author address: 

Univ. of New Mexico, Albuquerque, NM.

Abstract: 

Background: IE caused by CS is complicated by systemic embolization and requires antifungal and surgical therapy. We studied the effect of F and V against CS-infected platelet-fibrin clots that simulated endocardial vegetations (SEVs). Methods: Four CS bloodstream isolates: Candida albicans (CA), Candida glabrata (CG), Candida parapsilois (CP), and Candida tropicalis (CT). MICs of F and V against CS were performed in duplicate (CLSI, M27-A2). CS-infected SEVs were prepared as previously described using an initial inoculum of 1x106 CFU/g of SEV [Antimicrob. Agents Chemother. 1997;41:1359-63]. CS-infected SEVs were added to an in vitro pharmacodynamic model (PDM), which utilized yeast nitrogen broth-2% glucose and incubation at 35oC. The PDM simulated a 37.5 mg/kg PO q12h F and a 6 mg/kg PO q12h V regimens. Fungal densities in the SEVs were determined in quadruplicate at 0, 8, 24, 32, 48, and 72 hours (H) against F, V, and the growth control (GC). Scanning electron microscopy (SEM) was used for US characterization of SEVs. Results: CS had a F MIC of 0.125 μg/mL and V MIC of 0.015 μg/mL, except CG, which had a V MIC of 4.0 μg/mL. A significant change (mean ± SD) in fungal density (log10 CFU/mL) was noted with F (-3.3 ± 0.7) but not V (0.9 ± 1.4) treated SEVs compared to baseline (p
2006

abstract No: 

M-1778

Full conference title: 

46th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 46th