This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yeaman, M. R. Articles by Bayer, A. S. Search for Related Content PubMed PubMed Citation Articles by Yeaman, M. R. Articles by Bayer, A. S.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 2004, p. 3051-3056, Vol. 48, No. 8
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.8.3051-3056.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Susceptibility to Thrombin-Induced Platelet Microbicidal Protein Is Associated with Increased Fluconazole Efficacy against Experimental Endocarditis Due to Candida albicans

Division of Infectious Diseases, St. John's Cardiovascular Research Center, Harbor-UCLA Research and Education Institute, Torrance, California, 90502,¹ David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, 90059,² St. Mary's Medical Center, Long Beach, California 90801³

Received 24 January 2004/ Returned for modification 5 March 2004/ Accepted 26 March 2004

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-1^s) or resistance (tPMP-1^r) and efficacy of fluconazole (FLU) therapy of IE due to C. albicans. Candida IE was established in rabbits with either tPMP-1^s or tPMP-1^r 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-1^s strain than in those infected with the tPMP-1^r 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-1^s and tPMP-1^r C. albicans, with the extent of this effect greatest against the tPMP-1^s 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.

This article has been cited by other articles:

• Gank, K. D., Yeaman, M. R., Kojima, S., Yount, N. Y., Park, H., Edwards, J. E. Jr., Filler, S. G., Fu, Y. (2008). SSD1 Is Integral to Host Defense Peptide Resistance in Candida albicans. Eukaryot Cell 7: 1318-1327 [Abstract] [Full Text]  
• Xiong, Y. Q., Bayer, A. S., Elazegui, L., Yeaman, M. R. (2006). A Synthetic Congener Modeled on a Microbicidal Domain of Thrombin- Induced Platelet Microbicidal Protein 1 Recapitulates Staphylocidal Mechanisms of the Native Molecule. Antimicrob. Agents Chemother. 50: 3786-3792 [Abstract] [Full Text]