Background
Methods
Patients and setting
Clinical evaluation
Fungal strain
Isolation of genomic DNA and PCR amplification
Anti-fungal susceptibility testing
Statistical analysis
Results
Anti-fungal agent | Cumulative % inhibited at MIC (μg/ml) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
0.06 | 0.12 | 0.25 | 0.5 | 1 | 2 | 4 | 8 | 16 | 32 | |
Amphotericin B | 0 | 0 | 6.5 | 36.9 | 82.6 | 100 | ||||
Fluconazole | 0 | 0 | 0 | 8.7 | 28.3 | 74 | 95.7 | 100 | ||
Voriconazole | 8.7 | 52.2 | 91.3 | 100 |
Variables
|
Cured (%) (n = 26)
|
Not cured
#
(%) (n = 20)
|
p value
|
---|---|---|---|
Demographics
| |||
Male sex
|
19 (73.1)
|
13 (65)
|
0.75
|
Age >60 years
|
6 (23.1)
|
11 (55)
|
0.04
|
Coexisting conditions
| |||
AIDS
|
2 (8.3)
a
|
4 (22.2)
b
|
0.38
|
Solid tumor malignancy
|
2 (7.7)
|
4 (20)
|
0.38
|
Hematologic malignancy
|
3 (11.5)
|
1 (5)
|
0.62
|
Steroid usage
|
3 (11.5)
|
5 (25)
|
0.27
|
Liver cirrhosis
|
1 (3.8)
|
4 (20)
|
0.37
|
Chronic renal failure
|
2 (7.6)
|
1 (5)
|
1
|
Diabetic mellitus
|
8 (30.8)
|
4 (20)
|
0.51
|
COPD
|
4 (15.4)
|
0
|
0.12
|
Organ transplantation
|
1 (3.8)
|
0
|
1
|
No known predisposing factor
c
|
6 (23.1)
|
2 (10)
|
0.44
|
Previous anti-fungal therapy
d
|
3 (11.5)
|
4 (20)
|
0.68
|
Severity status
| |||
APACHE-II score
|
8.2 ± 2.4
|
10.4 ± 3.7
|
0.19
|
APACHE-II score ≥ 15
|
5 (19.2)
|
5 (25)
|
0.73
|
Shock
|
1 (3.8)
|
0
|
1
|
IICP
|
23 (88.5)
|
18 (90)
|
1
|
ICU admission
|
14 (53.8)
|
8 (40)
|
0.39
|
Initial laboratory data
| |||
India ink smear positive
|
12 (46.2)
|
11 (55)
|
0.77
|
CSF opening pressure (mmH
2
0)
|
248 ± 132
|
252 ± 136
|
0.58
|
CSF WBC count (/μL)
|
32.2 ± 40.6
|
28.8 ± 38.6
|
0.28
|
CSF CAT ≥ 1:1024
|
13 (50)
|
14 (70)
|
0.23
|
Serum CAT ≥ 1:1024
|
9 (34.6)
|
9 (45)
|
0.55
|
Concurrent cryptococcemia
|
6 (23.1)
|
6 (30)
|
0.74
|
Serotype B Cryptococcus neoformans isolate
|
4 (15.4)
|
1 (5)
|
0.37
|
Isolate resistant to fluconazole (MIC >8 μg/ml)
|
4 (15.4)
|
8 (40)
|
0.09
|
Isolate resistant to amphotericin B (MIC >1 μg/ml)
|
3 (11.5)
|
5 (25)
|
0.27
|
Treatment modality in induction therapy
| |||
Amphotericin B plus flucytosine
|
0
|
1 (5)
|
0.44
|
Amphotericin B plus fluconazole
|
10 (38.5)
|
13 (65)
|
0.14
|
Amphotericin B alone
|
12 (46.2)
|
5 (25)
|
0.22
|
Fluconazole alone
|
4 (15.4)
|
1 (5)
|
0.37
|
Variables
|
Cured (%) (n = 21)
|
Not cured
#
(%) (n = 25)
|
p-value
|
---|---|---|---|
Demographics
| |||
Male sex
|
15 (71.4)
|
17 (68)
|
1
|
Age >60 years
|
6 (28.6)
|
11 (44)
|
0.36
|
Co-existing conditions
| |||
AIDS
|
1 (5.3)
a
|
5 (21.7)
b
|
0.19
|
Solid tumor malignancy
|
2 (9.5)
|
4 (16)
|
0.67
|
Hematologic malignancy
|
3 (14.3)
|
1 (4)
|
0.32
|
Steroid usage
|
2 (9.5)
|
6 (24)
|
0.26
|
Liver cirrhosis
|
1 (4.8)
|
4 (16)
|
0.36
|
Chronic renal failure
|
1 (4.8)
|
2 (8)
|
1
|
Diabetic mellitus
|
7 (33.3)
|
5 (20)
|
0.34
|
COPD
|
3 (14.3)
|
1 (4)
|
0.32
|
Organ transplantation
|
1 (4.8)
|
0
|
0.46
|
No known predisposing factor
c
|
5 (23.8)
|
3 (12)
|
0.44
|
Previous anti-fungal therapy
d
|
2 (9.5)
|
5 (20)
|
0.43
|
Severity status
| |||
APACHE-II score
|
7.2 ±3.4
|
10 ± 2.2
|
0.39
|
APACHE-II score ≥ 15
|
4 (19.1)
|
6 (24)
|
0.74
|
Shock
|
1 (4.8)
|
0
|
0.46
|
IICP
|
19 (90.5)
|
22 (88)
|
1
|
ICU admission
|
12 (57.1)
|
10 (40)
|
0.38
|
Initial laboratory data
| |||
India ink smear positive
|
9 (42.9)
|
14 (56)
|
0.55
|
CSF opening pressure (mmH
2
0)
|
254 ± 116
|
246 ± 122
|
0.68
|
CSF WBC count (/μL)
|
30.4 ± 42.8
|
28.6 ± 32.4
|
0.26
|
CSF CAT ≥ 1:1024
|
11 (52.4)
|
16 (64)
|
0.55
|
Serum CAT ≥ 1:1024
|
8 (38.1)
|
10 (40)
|
1
|
Concurrent cryptococcemia
|
4 (19.1)
|
8 (32)
|
0.50
|
Serotype B Cryptococcus neoformans isolate
|
4 (19.1)
|
1 (4)
|
0.16
|
Isolate resistant to fluconazole (MIC >8 μg/ml)
|
1 (4.8)
|
11 (44)
|
<0.01*
|
Isolate resistant to amphotericin B (MIC >1 μg/ml)
|
2 (9.5)
|
6 (24)
|
0.26
|
Treatment modality in induction therapy
| |||
Amphotericin B plus flucytosine
|
0
|
1 (4)
|
1
|
Amphotericin B plus fluconazole
|
7 (33.3)
|
16 (64)
|
0.08
|
Amphotericin B alone
|
11 (52.4)
|
6 (24)
|
0.07
|
Fluconazole alone
|
3 (14.3)
|
2 (8)
|
0.65
|
Initial treatment
a
and outcome
b
|
No of patients/strains
|
No. of strains not susceptible to anti-fungal agent
c
| |
---|---|---|---|
AMB
|
FCZ
| ||
AMB + 5FC
| |||
Cure
| |||
Failure
| |||
Death
|
1
|
1
| |
AMB + FCZ
| |||
Cure
|
7
|
1
|
1
|
Failure
|
12
|
4
|
5
|
Death
|
4
|
1
| |
AMB alone
| |||
Cure
|
11
| ||
Failure
|
4
|
3
| |
Death
|
2
|
2
| |
FCZ alone
| |||
Cure
|
3
|
1
| |
Failure
|
1
| ||
Death
|
1
|
1
|