Biofilm Production by Candida Species and Inadequate Antifungal Therapy as Predictors of Mortality for Patients with Candidemia

DOI: 10.1128/JCM.00131-07

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FIG. 1.
Annual distribution of Candida species causing BSIs during a 5-year study period.
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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.
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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.

TABLE 1.

Epidemiological characteristics and outcomes of 294 patients with candidemia by type of fungal isolate

Variable (no. of patients [%])^a	Patients infected with:		P^b
Variable (no. of patients [%])^a	Candida albicans (n = 168)	Non-C. albicans Candida species (n = 126)	P^b
Age (yr) (mean ± SD)	64.9 ± 15.4	65.1 ± 13.7	0.90
Male sex	74 (44)	50 (39.6)	0.45
Hospital-acquired candidemia	154 (91.6)	108 (85.7)	0.10
Duration of hospitalization (no. of days) (mean ± SD)^c	47.7 ± 38.2	50.1 ± 42.6	0.60
Diabetes	32 (19)	26 (20.6)	0.73
Liver disease	16 (9.5)	14 (11.1)	0.65
Solid-organ cancer	76 (45.2)	42 (33.3)	0.03
Hematological malignancy	12 (7.1)	14 (11.1)	0.23
Neutropenia^d	10 (5.9)	8 (6.3)	0.88
Immunosuppressive therapy	82 (48.8)	38 (30.1)	0.001
Surgical admission	100 (59.5)	62 (49.2)	0.07
In the ICU at diagnosis	57 (33.9)	45 (35.7)	0.75
Indwelling urinary catheter	136 (80.9)	90 (71.4)	0.05
CVC	120 (71.4)	93 (73.8)	0.65
TPN	72 (42.8)	66 (52.3)	0.10
CVC-related candidemia	30 (17.8)	30 (23.8)	0.21
Mortality rate	97 (57.7)	57 (45.2)	0.03

↵ a Values are presented as the number (percentage) of patients with the specified characteristic, unless otherwise indicated.
↵ b P value comparing the value for patients infected with C. albicans to the value for patients infected with non-C. albicans Candida species.
↵ c For patients transferred from another hospital, the duration of hospitalization was calculated by the date of the first hospital admission.
↵ d White blood cell count of less than 0.5 × 10⁹ cells/liter.

TABLE 2.

Variables associated with mortality in 294 patients with candidemia

Characteristic (no. of patients [%])^a	No. of patients who:		OR (95% CI)	P^b
Characteristic (no. of patients [%])^a	Died (n = 154)	Survived (n = 140)	OR (95% CI)	P^b
Age (yr) (mean ± SD)	69 ± 12	59 ± 16		<0.001
Male sex	70 (45.4)	54 (38.5)	1.32 (0.81-2.17)	0.23
Hospital-acquired candidemia	144 (93.5)	118 (84.2)	2.68 (1.16-6.59)	0.01
Neutropenia^c	10 (6.5)	8 (5.7)	1.14 (0.39-3.44)	0.78
Immunosuppressive therapy	75 (48.7)	45 (32.1)	2.00 (1.21-3.31)	0.003
Duration of hospitalization (no. of days) (mean ± SD)^d	46 ± 39	51 ± 40		0.27
Surgical admission	87 (56.4)	75 (53.5)	1.12 (0.69-1.83)	0.61
In the ICU at diagnosis	52 (33.7)	50 (35.7)	0.91 (0.55-1.52)	0.72
TPN	72 (46.7)	66 (47.1)	0.98 (0.60-1.59)	0.94
CVC	123 (79.8)	90 (64.2)	2.20 (1.26-3.86)	0.003
Catheter-related candidemia	26 (16.8)	34 (24.2)	0.63 (0.34-1.16)	0.11
APACHE III score (mean ± SD)	38 ± 16	27 ± 17		<0.001
Species isolated
Candida albicans	97 (62.9)	71 (50.7)	1.65 (1.01-2.70)	0.03
Candida parapsilosis	24 (15.5)	40 (28.5)	0.46 (0.25-0.84)	0.007
Candida tropicalis	12 (7.8)	16 (11.4)	0.65 (0.27-1.54)	0.28
Candida glabrata	15 (9.7)	11 (7.8)	1.26 (0.52-3.16)	0.57
Other Candida species	6 (3.8)	2 (1.4)	1.44 (0.95-2.18)	0.19
Biofilm production by fungal isolate^e	56 (36.3)	24 (17.1)	2.76 (1.54-5.00)	<0.001
Inadequate antifungal therapy	30 (19.4)	13 (9.3)	2.36 (1.13-5.16)	0.01

↵ a Values are presented as the number (percentage) of patients with the specified characteristic, unless otherwise indicated.
↵ b P value comparing the value for patients who died to the value for patients who survived.
↵ c White blood cell count of less than 0.5 × 10⁹ cells/liter.
↵ d For patients transferred from another hospital, the duration of hospitalization was calculated by the date of the first hospital admission.
↵ e As assessed by %T and XTT absorbance determinations (see Materials and Methods for details).

TABLE 3.

Crude OR and 95% CI for mortality according to biofilm production by isolates of Candida species

Candida species	Patients infected by biofilm-positive isolate		Patients infected by biofilm-negative isolate		OR (95% CI)	P^a
Candida species	Total no.	No. (%) who died	Total no.	No. (%) who died	OR (95% CI)	P^a
C. albicans	38	32 (84.2)	130	65 (50)	3.90 (1.72-8.83)	<0.001
C. parapsilosis	14	10 (71.4)	50	14 (28)	4.16 (1.46-11.82)	0.003
C. tropicalis	20	8 (40)	8	4 (50)	0.88 (0.54-1.45)	0.62
C. glabrata	6	4 (66.6)	20	11 (55)	1.46 (0.32-6.62)	0.61
Other^b	2	2 (100)	6	4 (66.6)		0.34
Total	80	56 (70)	214	98 (45.7)	2.76 (1.55-5.00)	<0.001

↵ a P value comparing the number of patients who were infected with a biofilm-positive isolate and died to the number of patients infected with a biofilm-negative isolate and died.
↵ b Includes Candida guilliermondii (three patients), Candida krusei (two patients), and Candida spp. (three patients).