Susceptibility to thrombin-induced platelet microbicidal protein is associated with increased fluconazole efficacy against experimental endocarditis due to Candida albicans.

Abstract:

:Platelet microbicidal proteins (PMPs) are believed to be integral to host defense against endovascular infection. We previously demonstrated that susceptibility to thrombin-induced PMP 1 (tPMP-1) in vitro negatively influences Candida albicans virulence in the rabbit model of infective endocarditis (IE). This study evaluated the relationship between in vitro tPMP-1 susceptibility (tPMP-1s) or resistance (tPMP-1r) and efficacy of fluconazole (FLU) therapy of IE due to C. albicans. Candida IE was established in rabbits with either tPMP-1s or tPMP-1r strains. Treatment groups received FLU (100 mg/kg/day) intraperitoneally for 7 or 14 days; control animals received no therapy. At these time points, cardiac vegetations, kidneys, and spleens were quantitatively cultured to assess fungal burden. At both 7 and 14 days and in all target tissues, the extent of candidal clearance by FLU was greater in animals infected with the tPMP-1s strain than in those infected with the tPMP-1r strain. These differences were statistically significant in the spleen and kidney. Corroborating these in vivo data, FLU (a candidastatic agent), in combination with tPMP-1, exerted an enhanced fungicidal effect in vitro against tPMP-1s and tPMP-1r C. albicans, with the extent of this effect greatest against the tPMP-1s strain. Collectively, these results support the concept that tPMP-1 susceptibility contributes to the net efficacy of FLU against C. albicans IE in vivo, particularly in tissues in which platelets and tPMP-1 likely play significant roles in host defense.

authors

Yeaman MR,Cheng D,Desai B,Kupferwasser LI,Xiong YQ,Gank KD,Edwards JE Jr,Bayer AS

doi

10.1128/AAC.48.8.3051-3056.2004

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

3051-6

issue

8

eissn

0066-4804

issn

1098-6596

pii

48/8/3051

journal_volume

48

pub_type

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