Biofilm production by Candida species and inadequate antifungal therapy as predictors of mortality for patients with candidemia

Abstract

Nosocomial Candida bloodstream infections rank among infections with highest mortality rates. A retrospective cohort analysis was conducted at Catholic University Hospital to estimate the risk factors for mortality of patients with candidemia. We reviewed records for patients with a Candida bloodstream infection over a 5-year period (January 2000 through December 2004). Two hundred ninety-four patients (42.1% male; mean age +/- standard deviation, 65 +/- 12 years) were studied. Patients most commonly were admitted with a surgical diagnosis (162 patients [55.1%]), had a central venous catheter (213 [72.4%]), cancer (118 [40.1%]), or diabetes (58 [19.7%]). One hundred fifty-four (52.3%) patients died within 30 days. Of 294 patients, 168 (57.1%) were infected by Candida albicans, 64 (21.7%) by Candida parapsilosis, 28 (9.5%) by Candida tropicalis, and 26 (8.8%) by Candida glabrata. When fungal isolates were tested for biofilm formation capacity, biofilm production was most commonly observed for isolates of C. tropicalis (20 of 28 patients [71.4%]), followed by C. glabrata (6 of 26 [23.1%]), C. albicans (38 of 168 [22.6%]), and C. parapsilosis (14 of 64 [21.8%]). Multivariable analysis identified inadequate antifungal therapy (odds ratio [OR], 2.35; 95% confidence interval [95% CI], 1.09 to 5.10; P = 0.03), infection with overall biofilm-forming Candida species (OR, 2.33; 95% CI, 1.26 to 4.30; P = 0.007), and Acute Physiology and Chronic Health Evaluation III scores (OR, 1.03; 95% CI, 1.01 to 1.15; P < 0.001) as independent predictors of mortality. Notably, if mortality was analyzed according to the different biofilm-forming Candida species studied, only infections caused by C. albicans (P < 0.001) and C. parapsilosis (P = 0.003) correlated with increased mortality. Together with well-established factors, Candida biofilm production was therefore shown to be associated with greater mortality of patients with candidemia, probably by preventing complete organism eradication from the blood.

FIG. 1.

Annual distribution of Candida species causing BSIs during a 5-year study period.

FIG. 2.

Annual distribution of biofilm-producing Candida albicans (▴) and non-C. albicans Candida species (□) isolated from BSIs between 2000 and 2004. The amount of biofilm produced was determined by the %T and XTT reduction methods as described in Materials and Methods.

FIG. 3.

XTT formazan signal produced by 294 Candida isolates examined for biofilm formation ability. According to the %T results (see the text for details), isolates were classified as nonbiofilm producers or low- or high-biofilm producers. Differences in XTT activity among groups were statistically significant (P < 0.0001). Each symbol depicts the result for one Candida isolate; the black lines show the mean values.