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Abstract
We evaluated all Candida sp. bloodstream isolates obtained from patients admitted to 4 tertiary care hospitals between 1995 and 2003 in
the city of Sao Paulo, Brazil. Susceptibility to amphotericin B, 5-fluorocytosine, fluconazole (FCZ), itraconazole (ITZ), and voriconazole
(VCZ) was determined using the Clinical Laboratory Standards Institute broth microdilution method. We tested a total of 1000 strains,
including 400 strains of Candida albicans (40%), 243 of Candida tropicalis (24.3%), 238 of Candida parapsilosis (23.8%), 44 of C.
glabrata (4.4%), 30 of Candida guilliermondii (3%), and 25 of Candida rugosa (2.5%). Only 1.9% of the strains tested were susceptible in a
dose-dependent manner, and 0.2% of them were resistant to FCZ. Almost 100% of the strains were susceptible to VCZ. Despite that azole
resistance was a rare finding, a trend toward increased resistance among C. rugosa strains to FCZ and ITZ was noted.
D 2007 Elsevier Inc. All rights reserved.
Keywords: Candida spp.; Candidemia; Antifungal susceptibility testing; Resistance
1. Introduction
A progressive increase in the frequency of candidemia
has been observed worldwide, particularly among patients
receiving antibiotics, immunosuppressive therapy, or parenteral nutrition, as well as among patients exposed to invasive
medical procedures (Verduyn Lunel et al., 1999). Studies
conducted in tertiary care hospitals in different countries of
Europe and in the United States have shown incidence rates
of candidemia ranging from 0.17 to 0.76 and 0.28 to 0.96
per 1000 admissions, respectively (Kao et al., 1999;
Marchetti et al., 2004; Diekema et al., 2002; Richet et al.,
2002). It is worth mentioning that candidemia leads to an
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3. Results
3.1. Distribution of Candida spp.
Table 1 summarizes the distribution of 1000 Candida sp.
bloodstream isolates. Only a single candidemic episode for
each patient was considered for the study. Four hundred of
them were C. albicans (40%), 243 Candida tropicalis
(24.3%), 238 C. parapsilosis (23.8%), 44 C. glabrata
Table 1
Species distribution of 1000 Candida bloodstream isolates stratified in 2
periods: 1995 to 1999 and 2000 to 2003
Candida spp.
Period 1
(19951999),
n (%)
Period 2
(20002003),
n (%)
Total,
n (%)
C. albicans
C. tropicalis
C. parapsilosis
C. glabrata
C. guilliermondii
C. rugosa
C. krusei
Other Candida spp.
Total
129 (43)
74 (24.7)
58 (19.5)
16 (5.5)
12 (4)
6 (2)
1 (0.3)
3a (1)
299
271 (38.6)
169 (24.1)
180 (25.6)
28 (4)
18 (2.7)
19 (2.7)
5 (0.7)
11b (1.6)
701
400 (40)
243 (24.3)
238 (23.8)
44 (4.4)
30 (3)
25 (2.5)
6 (0.6)
14 (1.4)
1000
.18
.82
.03
.33
.22
.51
.47
.48
D.A. da Matta et al. / Diagnostic Microbiology and Infectious Disease 57 (2007) 399 404
401
Table 2
In vitro susceptibilities of 1000 Candida bloodstream isolates tested against FCZ, ITZ, and VCZ
Candida spp. (n)
C. albicans (400)
C. tropicalis (243)
C. parapsilosis (238)
C. glabrata (44)
C. guilliermondii (30)
C. rugosa (25)
C. krusei (6)d
Othere (14)
Total (1000)
a
b
c
d
e
FCZ
ITZ
VCZ
Ag/mL
Ag/mL
Ag/mL
MIC50/MIC90
Sa/SDDb/Rc
MIC50/MIC90
S/SDD/R
MIC50/MIC90
S/SDD/R
0.25/0.5
0.5/1
0.5/2
4/8
2/4
2/32
16/
2/2
0.5/2
100/0/0
100/0/0
100/0/0
93.2/2.3/4.5
96.7/3.3/0
56/44/0
0/100/0
100/0/0
97.9/1.9/0.2
0.03/0.06
0.03/0.06
0.03/0.06
0.25/1
0.25/0.25
0.03/0.5
0.25/
0.03/0.125
0.03/0.125
99.5/0.5/0
98.4/1.6/0
98.8/0.8/0.4
34.1/50/15.9
43.4/50/6.6
68/32/0
33.5/66.5/0
92.9/7.1/0
93.2/5.8/1
0.03/0.03
0.03/0.06
0.03/0.03
0.125/0.25
0.06/0.125
0.25/0.5
0.25/
0.03/0.06
0.03/0.06
100/0/0
100/0/0
100/0/0
93.2/2.3/4.5
100/0/0
100/0/0
100/0/0
100/0/0
99.7/0.1/0.2
3.3. Amphotericin B
None of the strains showed MIC values z 2 Ag/mL for
AMB, including the 5 strains of C. lusitaniae.
3.4. 5-Fluorocytosine
Twenty-five isolates (2.5%) were resistant to 5FC,
including 13 strains of C. tropicalis, 7 of C. albicans, 4
of C. parapsilosis, and 1 of C. krusei.
3.5. Fluconazole
All strains of C. albicans, C. tropicalis, C. parapsilosis,
C. pelliculosa , C. lusitaniae , C. zeylanoides, and
C. lipolytica strains had MIC values V 8 Ag/mL and were
classified as susceptible to FCZ. A total of 19 (1.9%) isolates
were considered SDD to FCZ, including 11 strains of
C. rugosa, 6 of C. krusei, 1 of C. guilliermondii, and 1 of
C. glabrata. Only 2 (0.2%) C. glabrata isolates were
resistant to this antifungal agent (MIC z 64 Ag/mL).
3.6. Itraconazole
A total of 58 (5.8%) isolates were SDD to ITZ, including
22 strains of C. glabrata, 15 of C. guilliermondii, 8 of
C. rugosa strains, 4 of C. krusei, 4 of C. tropicalis, 2 of
Table 3
Susceptibility profile of 1000 Candida bloodstream isolates tested against 5 antifungal drugs
Candida spp. (n1/n2)
5-Fluorocytosine
FCZ
ITZ
VCZ
C. albicans (129/271)
C. tropicalis (74/169)
C. parapsilosis (58/180)
C. glabrata (16/28)
C. guilliermondii (12/18)
C. rugosa (6/19)
Total (299/701)
100/100
100/100
100/100
100/100
100/100
100/100
100/100
96.9/98.9
97.3/91.1
98.3/97.2
100/100
100/100
100/100
97.4/96.3
100/100
100/100
100/100
100/89.3a
91.7/100
100/42b
99.3/97.3
99.2/99.6
97.3/98.8
96.5/99.5
50/28.6a
50/59
100/57.9b
93/93.3
100/100
100/100
100/100
100/89.3
100/100
100/100
100/99.6
a
b
Diferences were not statistically significant to fluconazole ( P = .55) and itraconazole ( P = .16).
Diferences were statistically significant to fluconazole ( P = .01) and itraconazole ( P = .06).
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403
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