Supplementary Table 1 Selected demography, comorbid medical, surgical and therapeutic
risk factors and outcome of adult candidemia patients admitted to 27 intensive care units
across India from April 2011 to September 2012
Characteristic
Candidemi
Characteristic
Candidem
a cases
ia cases
(n=913)
(n=913)
Demography
Therapeutic risk factors
Age (years) (median;
50.0 (34-
interquartile range)
63)
Males (%)
534 (58.5)
Steroid therapy (%)
164 (18.0)
Broad spectrum antibiotics
784 (85.9)
(%)
Females (%)
379 (41.5)
Received antibiotics (%)
849 (93.0)
Public sector (%)
377 (41.3)
1 antibiotic (%)
265 (29.0)
Private/corporate sector (%)
536 (58.7)
2 antibiotics (%)
298 (32.6)
3 antibiotics (%)
173 (18.9)
228 (25.0)
4 antibiotics (%)
73 (8.0)
209 (22.9)
5 antibiotics (%)
30 (3.3)
Comorbid medical conditions
Underlying respiratory
disease (%)
Underlying renal diseasea (%)
Renal failureb (%)
191 (20.9)
Underlying neurological
178 (19.5)
Cytotoxic chemotherapy (%)
20 (2.2)
138 (15.1)
Immunomodulator therapy
6 (0.7)
6 antibiotics (%)
10 (1.1)
disease (%)
Underlying CVD (%)
(%)
Underlying malignancy (%)
117 (12.8)
Antifungal exposure before
ICU admission
Underlying liver disease (%)
99 (10.8)
Prior antifungals (%)
143 (15.7)
Underlying GIT disease (%)
65 (7.1)
Days on prior antifungals
8.0 (5-13)
Liver (%)
99 (10.8
Pancreatitis (%)
62 (6.8)
Prior amphotericin B (%)
7/143 (4.9)
Neutropenia (%)
12 (1.3)
Days on prior amphotericin B
9.0 (3-19)
(median; interquartile range)
(median; interquartile range)
Transplant (%)
12 (1.3)
Prior anidulafungin (%)
4/143 (2.8)
HIV/AIDS (%)
4 (0.4)
Prior caspofungin (%)
11/143
(7.7)
Surgical procedures
Prior echinocandins (%)
15/143
(10.5)
Any surgery (%)
341 (37.3)
Days on prior echinocandins
11.0 (5-13)
(median; interquartile range)
GI surgery (%)
142 (15.6)
Prior fluconazole (%)
112/143
(78.3)
General surgery (%)
53 (5.8)
Prior posaconazole (%)
1/143 (0.7)
Neurosurgery (%)
45 (4.9)
Prior voriconazole (%)
12/143
(8.4)
Vascular surgery (%)
42 (4.6)
Prior azoles (%)
125/143
(87.4)
Genitourinary surgery (%)
25 (2.7)
Days on prior azoles (median;
7.0 (5-13)
interquartile range)
Orthopedic surgery (%)
19 (2.1)
Reasons for prior antifungals
Pancreatic surgery (%)
14 (1.5)
Prophylactic antifungals (%)
30/143
(20.9)
Obstetric surgery (%)
11 (1.2)
Empiric antifungals (%)
69/143
(48.3)
Hepatobiliary surgery (%)
9 (1.0)
Treatment after diagnosis (%)
11/143
(7.7)
Invasive procedures
Not mentioned (%)
33/143
(23.1)
Central venous catheterization 676 (74.0)
Outcome
(%)
CVC removed after
217/676
Length of stay in ICU
17.0 (10-
candidemia (%)
(32.1)
(median;interquartile range)
33)
Removed in <24 hours
59/217
Days to candidemia (median;
8.0 (4-15)
(%)
(27.2)
interquartile range)
Removed in 24-48 hours
59/217
Resolved (%)
251 (27.5)
(%)
(27.2)
Removed after >48 hours
99/217
Discharged (%)
390 (42.7)
(%)
(45.6)
483 (45.6)
Still admitted (%)
49 (5.4)
Total parenteral nutrition (%)
122 (13.4)
LAMA (%)
51 (5.6)
Dialysis before (%)
185 (20.3)
30-day crude mortality (%)
408 (44.7)
Urinary catheter (%)
693 (75.9)
30-day attributable mortality
179 (19.6)
Invasive mechanical
ventilation (%)
(%)
Drainage catheter(s) (%)
271 (29.7)
Abnormal chest X-ray (%)
58 (6.4)
APACHE - Median; (range)
17.0 (0-39)
SD = standard deviation, APACHE II = Acute Physiology and Chronic Health Evaluation
II, MODS = multi-organ dysfunction syndrome, CVD = cardiovascular disease, GIT =
gastrointestinal tract, CVC = central venous catheter, LAMA = left against medical advice,
a
Underlying renal disease was considered when the case had renal disease without going to
failure. Under the underlying disease other than renal failure the conditions include diabetic
nephropathy, glomerulonephritis, heptato renal syndrome, hydronephorosis,
pyelonephrosis, renal calculi, and haemolytic ureamic syndrome.
b
Acute renal failure (ARF) was defined as a abrupt loss of kidney function with measurable
increase in the serum creatinine concentration (usually relative increase of 50% or absolute
increase of 0.5 to 1.0 mg/dL). Chronic renal failure/kidney disease was defined when there
was loss of kidney function over months or years.
Supplementary Text:
Underlying diseases and risk factors: Gastrointestinal conditions included illnesses of the
gastrointestinal tract (65; 7.1%), liver (99; 10.8%) and pancreatitis (62; 6.8%). Neutropenia
(12; 1.3%) and HIV/AIDS (4; 0.4%) were uncommon (Supplementary Table 1).
Antibiotic exposure: The predominant antibiotic exposure was to carbapenems (393;
43.0%) followed by penicillins (289; 31.7%), cephalosporins (222; 24.3%), glycopeptides
(209; 22.9%), aminoglycosides (139; 15.2%), quinolones (117; 12.8%) and polymyxins
(108; 11.8%).
Break through candidemia: A total of 64 patients had overlapping periods of previous
antifungals with current ICU admission for at least 4 days. Of these only 13 were on
prophylactic treatment and the rest were on empiric treatment. C. tropicalis was seen in 6,
C. albicans in 4, and C. glabrata in 3. Of these 6 died and 7 were alive at 30 days after
onset.
Supplementary Table 2 Antifungal treatment received by adult candidemia intensive care
patients after definitive microbiological diagnosis in the ICU
Characteristic
Candidemi
Characteristic
Candidemi
a cases
a cases
(n=913)
(n=913)
Treatment after diagnosis in
Change in treatment
ICU
Antifungal treatment (%)
547 (59.9)
Antifungal changed (%)
81/547
(14.8)
Days on antifungals (median;
9.0 (5-15)
AFST (%)
17/81 (20.9)
72/547
Cost (%)
3/81 (3.7)
8.0 (5-12)
De-escalation (%)
13/81 (16.0)
Liposomal amphotericin B (%)
7/547 (1.3)
No reason (%)
4/81 (4.9)
Anidulafungin (%)
22/547
Switch to oral (%)
1/81 (1.2)
interquartile range)
Amphotericin B (%)
(13.2)
Days on amphotericin B
(median; interquartile range)
(4.0)
Caspofungin (%)
72/547
Toxicity (%)
7/81 (8.6)
36/81 (44.4)
(13.2)
Micafungin (%)
7/547 (1.3)
Escalation (%)
Echinocandins (%)
100/547
Adverse reactions
(18.3)
Days on echinocandins
6.0 (3.75-
(median; range)
14)
Fluconazole (%)
359/547
Acute renal failure (%)
5/547 (0.9)
Bradycardia (%)
1/547 (0.2)
Hypokalemia (%)
2/547 (0.4)
(65.6)
Posaconazole (%)
1/547 (0.2)
Voriconazole (%)
40/547
(7.3)
Azoles (%)
394/547
(72.0)
Days on azoles (median; range)
10.0 (5-15)
SD standard deviation, AFST antifungal susceptibility test.
Supplementary Table 3 Candidemia risk factors significantly associated with 30-day
crude mortality of adult candidemia intensive care patients
Risk factor
30-day crude mortality
Survived (n=505)
Died (n=408)
p
Age (mean ± SD)
48.4 ± 17.4
51.3 ± 18.0
0.014
Public sector hospital (%)
188 (37.2)
189 (46.3)
0.006
APACHE II (mean ± SD)
15.6 ± 5.5
18.7 ± 5.7
<0.001
Length of ICU stay (mean ± SD)
28.7 ± 25.4
17.9 ± 14.9
<0.001
Presentation with sepsis (%)
48 (9.5)
64 (15.7)
0.006
Presentation with shock (%)
13 (2.6)
24 (5.9)
0.017
Presentation with MODS (%)
8 (1.6)
17 (4.2)
0.023
Underlying liver disease (%)
43 (8.5)
56 (13.7)
0.014
Underlying respiratory disease (%)
102 (20.2)
126 (30.9)
<0.001
Underlying renal disease (%)
89 (17.6)
120 (29.4)
<0.001
Acute renal failure (%)
54 (10.7)
74 (18.1)
0.002
Chronic renal failure (%)
25 (5.0)
38 (9.3)
0.012
Renal failure (%)
79 (15.6)
112 (27.5)
<0.001
Neutrophil count (day 30) (mean ± SD)
5655.5 ± 2845.9
6761.0 ± 5621.6
0.012
Serum creatinine (day 30) (mean ± SD)
1.3 ± 1.1
2.3 ± 1.8
<0.001
Dialysis (%)
76 (15.0)
109 (26.7)
<0.001
Hemodialysis (%)
67 (13.3)
91 (22.3)
<0.001
Peritoneal dialysis (%)
7 (1.4)
23 (5.6)
0.001
Invasive mechanical ventilation (%)
240 (55.2)
243 (68.6)
<0.001
Corticosteroid therapy (%)
67 (13.3)
97 (23.8)
<0.001
Colistin therapy (%)
37 (7.3)
57 (14.0)
0.001
Clindamycin therapy (%)
5 (1.0)
22 (5.4)
<0.001
Polymyxin(s) therapya (%)
47 (9.3)
61 (15.0)
0.010
Secondary bacterial infection (%)
48 (9.5)
62 (15.2)
0.010
Acinetobacter spp. sepsis (%)
10 (2.0)
20 (4.9)
0.015
GNB infection (%)
39 (7.7)
55 (13.5)
0.006
338 (66.9)
209 (51.2)
<0.001
7.9 ± 9.4
3.8 ± 6.1
<0.001
257 (50.9)
137 (33.6)
<0.001
Days on azolesb (mean ± SD)
5.7 ± 8.3
2.6 ± 5.6
<0.001
Abnormal chest X-rayc (%)
22 (4.4)
36 (8.8)
0.006
Antifungal treatment (%)
Days on antifungalsb (mean ± SD)
Treatment with azoles (%)
SD standard deviation, APACHE II Acute Physiology and Chronic Health Evaluation II,
MODS multi-organ dysfunction syndrome, GNB gram negative bacteria.
a
Polymyxin(s) refer to any exposure to colistin and/or polymyxin B.
b
c
Therapy instituted after definitive microbiological diagnosis of candidemia in the ICU.
An abnormal chest X-ray includes, abnormal opacities, consolidation, effusions and
pneumothorax.
Legend
Supplementary Fig. 1 Percentage of various Candida species isolated from 918 adult
candidemia intensive care patients highlighting the eight species contributing the highest
burden. "Others" comprise 22 less common Candida species found in our patients