Open AccessAssociation of Fluconazole Area under the Concentration-Time Curve/MIC and Dose/MIC Ratios with Mortality in Nonneutropenic Patients with Candidemia
Author(s) -
Manjunath P. Pai,
Robin S. Turpin,
Kevin W. Garey
Publication year - 2007
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00474-06
Subject(s) - fluconazole , fungemia , candida glabrata , candida albicans , corpus albicans , microbiology and biotechnology , candida tropicalis , candida parapsilosis , minimum inhibitory concentration , biology , medicine , antibiotics , antifungal
The present study tested in vitro susceptibility ofCandida bloodstream isolates to fluconazole to determine if the ratio of the fluconazole area under the concentration-time curve (AUC) or weight-normalized daily dose (dosewn ) to MIC correlated with mortality. Fluconazole susceptibility and outcome data were determined for 77 patients with a positiveCandida blood culture between 2002 and 2005. The most commonly isolatedCandida species wereC. albicans (64%),C. glabrata (14%),C. parapsilosis (8%),C. tropicalis (6%), andC. lusitaniae (4%). Only two isolates were classified as fluconazole resistant by the CLSI M27-A2 method. Fluconazole MICs were highest againstC. glabrata relative to otherCandida 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 ≥ 16 μg/ml) compared to 18% for patients infected with susceptible (MIC ≤ 8 μg/ml) isolates (P = 0.17). The fluconazole dosewn /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-susceptibleCandida isolates has the potential to increase the risk of mortality associated with candidemia.