Effects of Voriconazole and Cytokines on Intracellular Killing of Candida parapsilosis and Candida tropicalis with Reduced Susceptibility to Fluconazole in Human Monocyte-derived Macrophages (MDM)

A.L. BALTCH, MD1,2, W.J. RITZ, MS1,2, L.H. BOPP, PhD1, P.B. MICHELSEN, ScD1,2, R.P. SMITH, MD1,2;

Author address: 

1Stratton Vet. Med. Ctr., Albany, NY, 2Albany Med. Coll., Albany, NY.

Abstract: 

Background: Tissue infections and disseminated candidiasis caused by fluconazole-resistant (FluR) C. parapsilosis (Cpa) and C. tropicalis (Ctr) are increasingly common causes of morbidity and mortality. We investigated intracellular killing by voriconazole (Vor) of Cpa and Ctr with reduced susceptibilities to Flu in MDM and in MDM activated by GM-CSF or IFN-g. Methods: Three strains each of Cpa (MICs, mg/ml: Flu, 168722;64; Vor, 0.58722;1) and Ctr (MICs, mg/ml: Flu, 88722;32; Vor, 1) were used. MDM monolayers, established using monocytes from healthy volunteers, were incubated for 18 h ± GM-CSF (100 U/ml) or IFN-g (1000 U/ml), and infected with opsonized yeast (MOI = 0.01). Infected monolayers were then washed once and incubated with or without GM-CSF or IFN-g and Vor (2.5x MIC for Cpa, 5x MIC for Ctr). These Vor concentrations were chosen because they were moderately inhibitory intracellularly. MDM were lysed at 0, 24, or 48 h and viable yeast in the lysates were enumerated. Results: (1) treatment of infected MDM with Vor alone resulted in significant inhibition or killing of all Cpa and Ctr strains at both 24 and 48 h (P
2006

abstract No: 

575

Full conference title: 

Infectious Diseases Society of America, 44th Annual Meeting
    • IDSA 44th