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J Med Microbiol 55 (2006), 865-870; DOI: 10.1099/jmm.0.46393-0
© 2006 Society for General Microbiology
ISSN 1473-5644

Antifungal effect of voriconazole on intracellular Candida glabrata, Candida krusei and Candida parapsilosis in human monocyte-derived macrophages

Lawrence H. Bopp1, Aldona L. Baltch1,2, William J. Ritz1,2, Phyllis B. Michelsen1,2 and Raymond P. Smith1,2

Infectious Disease Research Laboratory, Stratton Veterans Affairs Medical Center1 , and Albany Medical College2 , Albany, NY 12208, USA

Correspondence
Aldona L. Baltch
aldona.baltch{at}med.va.gov

Received 1 November 2005
Accepted 22 March 2006

Infections caused by Candida species other than Candida albicans are increasingly common, and decreased susceptibility to azoles has made them more difficult to treat. Since phagocytic killing is important in elimination of Candida infections, intracellular killing of fluconazole-resistant Candida glabrata, Candida krusei and Candida parapsilosis (four strains each) by voriconazole was investigated in human monocyte-derived macrophages (MDMs). MDMs were infected with Candida, and voriconazole was then added. MDMs were lysed at 0, 24 or 48 h after infection, and viable Candida in the lysates enumerated. Compared to the starting inoculum, the number of viable intracellular C. parapsilosis and C. glabrata in untreated MDMs increased to 28 121 and 351 %, respectively, in 48 h. In contrast, the number of C. krusei decreased to 42 %. In MDMs treated with voriconazole, the decrease in viable count was dependent upon drug concentration. At 48 h, C. glabrata was killed only at 5x MIC (P<0.05), C. krusei was killed at all voriconazole concentrations, while C. parapsilosis was inhibited at 0.5 and 1x MIC and killed at >=2.5x MIC (P<0.05). The data show that intracellular growth and survival of these Candida species in the absence or presence of voriconazole vary markedly. The activity of voriconazole depends on the concentration of the drug and the time of exposure. For the 12 Candida strains studied, regression curves show that the maximum intracellular anticandidal activity of voriconazole was reached at 3.5–5x MIC.

Abbreviations: MDM, human monocyte-derived macrophage.




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