Antifungal susceptibility testing of Candida isolates from the Candida surveillance study.

Candida species are a common cause of nosocomial bloodstream infections. Recent surveillance has shown an increase in the relative proportion of infections caused by Candida glabrata, which has reduced susceptibility to fluconazole. We undertook sentinel surveillance with antifungal susceptibility testing to monitor the trends in the proportions of various Candida species causing invasive disease. Forty-one institutions participated in the Candida Surveillance Study. All isolates were submitted to a central laboratory for identification and susceptibility testing. Susceptibility testing was performed in compliance with CLSI guidelines using a custom, broth dilution, microtiter system. There were 5,900 isolates submitted for identification and antifungal susceptibility testing. The distribution of species was as follows: C. albicans, 2,567 (43.5%) isolates; C. glabrata, 1,464 (24.8%) isolates; C. parapsilosis, 1,048 (17.8%) isolates; C. tropicalis, 527 (8.9%) isolates; C. krusei, 109 (1.9%) isolates; C. lusitaniae, 76 (1.3%) isolates; and other Candida species, 109 (1.9%) isolates. Resistance to fluconazole occurred in 1.2% of C. albicans isolates, 5.9% of C. glabrata isolates, 0.3% of C. parapsilosis isolates, and 0.4% of C. tropicalis isolates. Resistance to fluconazole was highly predictive of resistance to voriconazole. Resistance to echinocandins was rarely found, occurring in only 0.2% of all isolates. The rate of fluconazole susceptibility increased significantly from 87.5% in 2005 to 97.4% in 2007. The proportion of cases of disease caused by various Candida species did not change appreciably between 2004 and 2007, and the rate of antifungal susceptibility was high.

A cytokine promoter/yellow fluorescent protein reporter transgene serves as an early activation marker of lymphocyte subsets.

A mouse containing an IL-4 promoter linked to the yellow fluorescent protein (YFP) reporter transgene was created to follow aspects of lymphocyte development and function. Following stimulation with phorbol 12-myristate 13-acetate and ionomycin, anti-CD3/CD28, antigen-specific peptide, or allogeneic cells, both CD4 and CD8 T cells expressed the transgene within 24h in a manner that was consistent with cellular activation markers. Transgene induction was inhibited by cyclosporine and FK506, suggesting that its activation occurs in an NFAT-dependent manner. B lymphocytes were also able to express the transgene when stimulated with LPS. This induction was inhibited in part by rapamycin. The results suggest that this transgene can function as an indicator of lymphocyte activation. Because YFP is not toxic and requires no preparation of the cells to view the reporter gene, this system provides a unique tool to follow lymphocyte activation in a number of model systems, such as those involving transplantation, allergy, and vaccine development.