Abstract
The present study tested in vitro susceptibility of Candida bloodstream isolates to fluconazole to determine if the ratio of the fluconazole area under the concentration-time curve (AUC) or weight-normalized daily dose (dose(wn)) to MIC correlated with mortality. Fluconazole susceptibility and outcome data were determined for 77 patients with a positive Candida blood culture between 2002 and 2005. The most commonly isolated Candida species were C. albicans (64%), C. glabrata (14%), C. parapsilosis (8%), C. tropicalis (6%), and C. lusitaniae (4%). Only two isolates were classified as fluconazole resistant by the CLSI M27-A2 method. Fluconazole MICs were highest against C. glabrata relative to other Candida species. Overall the crude mortality assessed at hospital discharge was 19.4% (n = 15). Mortality rates by species were as follows: C. albicans, 16.3%; C. glabrata, 36.4%; C. parapsilosis, 0%; C. tropicalis, 0%; C. lusitaniae, 33.3%. A mortality rate of 50% was noted among patients infected with nonsusceptible isolates (MIC > or = 16 microg/ml) compared to 18% for patients infected with susceptible (MIC < or = 8 microg/ml) isolates (P = 0.17). The fluconazole dose(wn)/MIC (24-h) values were significantly higher for the 62 survivors (13.3 +/- 10.5 [mean +/- standard deviation]) compared to the 15 nonsurvivors (7.0 +/- 8.0) (P = 0.03). The fluconazole AUC/MIC (24 h) values also trended higher for survivors (775 +/- 739) compared to nonsurvivors (589 +/- 715) (P = 0.09). These data support the dose-dependent properties of fluconazole. Underdosing fluconazole against less-susceptible Candida isolates has the potential to increase the risk of mortality associated with candidemia.