Activities and ultrastructural effects of antifungal combinations against simulated Candida endocardial vegetations.

Antimicrobial Agents and Chemotherapy
Manjunath P PaiMichael N Spilde

Abstract

In vitro pharmacodynamic model (PDM) simulation of serum antifungal concentrations may predict the value of combination antifungal regimens against Candida sp. endocarditis. We investigated the effects of combinations of flucytosine (5FC), micafungin (Mica), and voriconazole (Vor) against Candida-infected human platelet-fibrin clots, used as simulated endocardial vegetations (SEVs). Single clinical bloodstream isolates of Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis were used. All four isolates were susceptible to 5FC, while C. glabrata was resistant to Vor and C. tropicalis had a paradoxical resistance phenotype to Mica. The SEVs were prepared with an initial inoculum of 1 x 10(6) CFU/g of SEV and added to a PDM, which utilized yeast nitrogen broth-2% glucose and incubation at 35 degrees C and simulated antifungal pharmacokinetic profiles. Fungal densities in the SEVs were determined in quadruplicate over 72 h. Scanning electron microscopy (SEM) was used to evaluate treatment and control SEVs. Vor was the least active single agent against all Candida spp. except for C. parapsilosis, where it was comparable to Mica. In contrast, 5FC was the most active against all Candida spp. except for C. t...Continue Reading

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Citations

Sep 17, 2010·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·R CamilliL Baldassarri
May 26, 2009·Revista iberoamericana de micología·Guillermo QuindósJavier Pemán
May 26, 2009·Revista iberoamericana de micología·Guillermo QuindósElena Eraso
Mar 25, 2009·Antimicrobial Agents and Chemotherapy·Manjunath P Pai
Apr 1, 2011·Enfermedades infecciosas y microbiología clínica·Miguel Montejo, Guillermo Quindós
Aug 21, 2010·Journal of Medical Microbiology·Shanmugam Hemaiswarya, Mukesh Doble
Nov 11, 2014·Critical Reviews in Microbiology·Maria Elisa RodriguesMariana Henriques

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