Original Article

Epidemiology of Candida blood stream infections: experience of a tertiary

care centre in North India
Jagdish Chander, Nidhi Singla, Shailpreet Kaur Sidhu, Satinder Gombar
Departments of Microbiology and Anaesthesia and Intensive Care, Government Medical College Hospital,
Chandigarh, India
Abstract
Introduction: Bloodstream infections due to Candida species are becoming a major cause of morbidity and mortality in hospitalized patients.
The spectrum of candidemia has changed with the emergence of non-albicans Candida species, especially among critically ill patients.
Methodology: In a retrospective study (July 2009 to December 2009) on candidemia, various Candida species isolated from blood cultures
were characterized and studied along with the determination of their antifungal susceptibility to amphotericin B, itraconazole, and
fluconazole by Etest. Probable risk factors for patients in the intensive care unit (ICU) presenting with candidemia were also analyzed.
Results: During the study period, a total of 4651 samples were received, out of which 468 samples (10.06%) were positive for growth of
organisms: 441 (94.20%) aerobic bacterial pathogens and 27 (5.79%) Candida species. The most common Candida spp. isolate was C.
tropicalis (40.8%) followed by C. albicans (29.6%), C. glabrata (18.5%) and others (11.1%). Out of the 27 Candida strains, 24 (88.9%) were
isolated from patients treated in the ICU. Among these, association of previous use of broad-spectrum antibiotics in 22 patients (91.6%) and
central line catheter insertion in 20 patients (83.3%) were found to be statistically significant as compared to non-candidemia patients (p
<0.05). Antifungal susceptibility testing of the isolates revealed a lower level of drug resistance to amphotericin B (18.5% of the isolates)
versus 77.8% resistance to fluconazole.
Conclusion: Rapid changes in the rate of infection, potential risk factors, and emergence of non-albicans Candida demand continued
surveillance of this serious bloodstream fungal infection.

Key words: candidemia; epidemiology; ICU; Candida albicans; non-albicans Candida

J Infect Dev Ctries 2013; 7(9):670-675. doi:10.3855/jidc.2623
(Received 04 March 2012 Accepted 12 December 2012)
Copyright 2013 Chander et al. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction
Candida species are the fourth most common
cause of bloodstream infections and are the leading
cause of invasive fungal infections among hospitalized
patients [1]. Candidemia is a life-threatening fungal
infection associated with a mortality rate of 38%; it
also prolongs hospital stays by as much as 30 days and
increases the cost of medical care [2]. The frequent use
of antibiotics, central venous catheters and other
invasive devices, abdominal surgery and stays in the
intensive care unit (ICU) puts patients at a high risk of
infection with Candida, which has been shown to have
the shortest survival prospects of any bloodstream
infection [3]. The spectrum of candidemia has changed
with the emergence of non-albicans Candida (NAC)
species, a strain with the threat of increased mortality
and antifungal drug resistance, especially in
immunocompromised and severely ill patients [4]. It is
very important to identify Candida to the species level
to optimize the selection of the antifungal agent. More

importantly, intrinsic and emerging resistance to

azoles represents a major challenge for empirical,
therapeutic, and prophylactic strategies. The changing
scenario has necessitated routine antifungal
susceptibility testing since both in vitro resistance and
toxicity issues must be considered when selecting an
antifungal agent for therapy [5].
Methodology
The Government College Medical Hospital,
Chandigarh, is a tertiary health-care centre with a 14bed ICU (adult, combined medical, and surgical). The
ICU is run by a full-fledged Department of
Anaesthesia and Intensive Care with round-the-clock
available faculty, residents, and paramedical staff.
There is an institutional antibiotic policy in place and
strict infection control practices are regularly
followed.

Chander et al. Epidemiology of candidemia

The present retrospective study was conducted by

the Department of Microbiology over a period of six
months (from July 2009 to December 2009). During
this time period, the department received a total of
4651 samples on which blood culture and sensitivity
testing were performed. Blood for culture was
collected under strict aseptic conditions. A total of 5
mL of blood was added to each of two bottles
containing sodium polyanethole sulfonate (SPS) broth
and bile broth (Hi-Media Laboratories, Mumbai,
India). Both bottles were incubated aerobically at 37C
for seven days. Routine subculturing was done on 5%
sheep blood agar and MacConkey agar after 24 hours,
48 hours, and then at seven days. In between these
points, subculturing was done only if there was visible
turbidity. The aerobic bacterial isolates were further
identified based on standard microbiological
techniques [6].
The culture bottles that tested positive for yeasts
were subcultured on Sabouraud dextrose agar and the
yeasts were identified by standard mycological
techniques, namely germ-tube test, morphology on
cornmeal agar, color and colony characteristics on
CHROMAgar
Candida
medium
(Hi-Media
Laboratories,
Mumbai,
India),
carbohydrate
assimilation and fermentation tests (Discs, media
procured from Hi-Media Laboratories, Pvt. Ltd.
Mumbai, India). The antifungal susceptibility pattern
of the isolates was evaluated by the Etest (AB Biodisk,
Solna, Sweden) for amphotericin B, fluconazole and
itraconazole, on Mueller-Hinton agar supplemented
with 2% glucose. The zone diameter endpoints were
read at the complete inhibition for amphotericin B. In
the case of azoles, the inhibition zone usually has a
diffuse zone edge; therefore, the reading was taken at a
point showing significant inhibition or marked
decrease in growth intensity, usually corresponding
with about 80% inhibition of growth. MIC breakpoints
8 mg/L for fluconazole and 0.12 mg/L for
itraconazole were interpreted as susceptible; 16-32
mg/L and 0.25-0.5 mg/L as dose-dependent
susceptible; and 64 mg/L and 1 mg/L as resistant,
respectively. For amphotericin B, strains were
considered susceptible if MIC was 1 mg/L and
resistant if 2 mg/L based on the criteria of the
Clinical Laboratory Standards Institute [7]. The
standard strains used were C. parapsilosis (ATCC
22019, (Hi-Media Laboratories, Mumbai, India) and
C. albicans ATCC 90028 (Hi-Media Laboratories,
Mumbai, India).
An episode of candidemia was identified when the
Candida was isolated from the blood culture of the

J Infect Dev Ctries 2013; 7(9):670-675.

patient; the second episode was defined if it occurred

at least 30 days after the first episode. Clinical data of
all candidemia patients were recorded on standard
forms and analyzed. Medical history and probable risk
factors such as underlying illness, presence of central
venous catheters, total parenteral nutrition, prior use of
antimicrobials, cancer chemotherapy, use of
corticosteroids, diabetes mellitus, abdominal surgery,
neutropenia, any invasive procedure or devices, and
duration of ICU stay were also recorded. Chi square
test was used to determine the association of various
risk factors in candidemia patients and noncandidemia patients. The p value was calculated and a
p value of less than 0.05 was considered statistically
significant.
Results
During the study period, a total of 4651 samples
were received in the department for processing, of
which 468 samples (10.06%) appeared to be culture
positive. Among these 468 isolates, 441 (94.20%)
were aerobic bacterial pathogens and 27 (5.79%) were
organisms belonging to Candida species. Among
aerobic bacterial pathogens, the most common isolates
by morphology, Gram staining, culture characteristics
and biochemical reactions were Acinetobacter
calcoaceticus baumanii complex (n = 115; 26.07%)
followed by Staphylococcus aureus (n = 92; 20.86%),
Klebsiella pneumoniae (n = 82; 18.59%),
Enterococcus spp. (n = 51; 11.56%), Salmonella Typhi
(n = 37; 8.39%), Pseudomonas aeruginosa (n = 25;
5.66%), Escherichia coli (n = 11; 2.49%), Citrobacter
spp. (n = 9; 2.04%), and others. Among Candida, C.
tropicalis was the most frequently isolated species (n =
11; 40.74%), followed by C. albicans (n = 8; 29.62%),
C. glabrata (n = 5; 18.51%), C. parapsilosis (n = 1;
3.70%), and other species which that could not be
identified (n = 2; 7.40%). Concomitant candidemia
and bacteremia was observed in five patients (two with
Pseudomonas
aeruginosa
and
Acinetobacter
calcoaceticus-baumannii complex and one with
Klebsiella pneumoniae).
All episodes of candidemia were nosocomial and
occurred 48 hours after admission to the hospital. Of
these, 24 (88.9%) occurred in patients admitted to the
ICU, while only 3 episodes (11.1%) occurred in
patients in other hospital wards. As most of the cases
were from the ICU, the presence of various risk factors
between those presenting with candidemia and those
without candidemia during the same time period were
compared (Table 1). The most common factors
associated with candidemia were the use of broad671

Chander et al. Epidemiology of candidemia

J Infect Dev Ctries 2013; 7(9):670-675.

Table 1. Association of various risk factors for candidemia in ICU patients (n = 205)
Number of patients with
candidemia in ICU (24)
22

Number of patients without

candidemia in ICU (181)
115

p < 0.05

Central Venous Catheters

20

104

p < 0.05

Total parenteral nutrition

16

90

ns

Candida colonization in urine

14

88

ns

Major Surgical Procedure (in prior 30 days)

10

74

ns

Use of prophylactic antifungal agents

28

ns

Neutropenia
Use of corticosteroids/
Immunosuppressive agents
Diabetes mellitus

21

ns

39

ns

40

ns

Chronic renal failure

24

ns

Length of stay in ICU (> 15 days)

22

60

p < 0.05

Risk Factors
Use of antimicrobials (in prior 2 weeks)

spectrum antimicrobial agents in 22 (91.6%) and

central line catheters in 20 (83.3%). The association
was found to be statistically significant with p < 0.05.
Candidemia was also found to be associated with the
increased duration of ICU stay in these patients, with
most of the patients staying for more than 15 days in
the candidemia group (p < 0.05 as compared to noncandidemia patients).
The association of various risk factors among C.
albicans and non-albicans Candida group were also
compared. Results are given in Table 2.
Antifungal susceptibility testing revealed a lower
level of resistance to amphotericin B: 5 (18.5%) in
comparison to 17 (62.9%), and 21 (77.8%) of the
strains were found to be resistant to itraconazole and
fluconazole, respectively. Notably, all strains of C.
glabrata were found to be resistant to fluconazole and
only 2 (40.0%) strains were susceptible to
amphotericin B, while all strains of C. albicans were
susceptible to amphotericin B and 5 (62.5%) were
resistant to fluconazole. Among C. tropicalis, 9
(81.8%) strains were resistant to fluconazole and 8
(72.7%) were resistant to itraconazole. The antifungal
resistance pattern of the isolates is shown in Table 3.
Of the 27 episodes, 15 were treated with antifungal
agents; 12 episodes were not treated with antifungals
because patients were transferred to other hospitals or
died before a final diagnosis could be made, or no
reason was documented in their files.
The mortality was found to be 40.7% (11/27). Of
the patients who died, ten were from the ICU and one
was from a pediatric emergency ward. Out of 11, 7

p value

(63.6%) patients had candidemia due to non-albicans

Candida spp. The direct correlation of candidemia as
the cause of death in any of the patients could not be
ascertained due to multiple underlying pathologies.
Discussion
The spectrum of candidemia has changed with
the emergence of non-albicans Candida species and
with acquired antifungal resistance assisted by an
increase in the high-risk population. This study
highlights the prevalence of candidemia among the
hospitalized patients and its correlation to the wellknown risk factors. Moreover, the predominance of
non-albicans Candida species over C. albicans was a
notable feature as more than 70% of bloodstream
infections were caused by non-albicans Candida. In
this study, C. tropicalis was the most common isolate
(40.74%) followed by C. albicans (29.6%) and C.
glabrata (18.5%). Earlier data clearly shows that both
the incidence of nosocomial candidemia and the
proportion of bloodstream infections due to nonalbicans Candida, particularly C. tropicalis, C.
glabrata and C. parapsilosis, have increased [8-10].
This change in pattern has been partly attributed to
increased immune suppression resulting in higher
numbers of susceptible immunocompromised patients
and also to the prophylactic use of antifungal agents in
critically ill patients [11,12].
Hospitalization (especially in the ICU),
placement of central venous catheters, and previous
antimicrobial therapies played significant roles in the
development of candidemia in this setting (Table 1).
672

Chander et al. Epidemiology of candidemia

J Infect Dev Ctries 2013; 7(9):670-675.

Table 2. Comparison of risk factors between C. albicans and Non-albicans Candida (NAC) species
Risk Factors

Number
of
episodes
of
candidemia
(%)

C. albicans
(8)

Non-albicans Candida (19)

C. tropicalis
(11)
0

C. glabrata
(5)
3

Others
(3)
0

Total
NAC
3

Age > 55 years

5 (18.5)

Stay in ICU/ other ward

24 (88.9)

7/1

9/2

17/2

Use of antimicrobials (in prior 2 weeks)

25 (92.5)

11

19

Central Venous Catheters

22 (81.4)

16

Total parenteral nutrition

16 (59.2)

11

Candida colonization in urine

15 (55.5)

Major Surgical Procedure

(in prior 30 days)
Use of prophylactic antifungal agents

11 (40.7)

9 (33.3)

Neutropenia

6 (29.6)

Use of corticosteroids/
Immunosuppressive agents
Others (Diabetes mellitus, Chronic renal
failure, Malignancy)
Expired

6 (22.2)

6 (22.2)

11 (40.7)

Table 3. Antifungal resistance pattern of Candida isolates by Etest

Antifungal agent
Amphotericin B

C. tropicalis
(n = 11)
2

C. albicans
(n = 8)
0

C. glabrata
(n = 5)
3

C. parapsilosis
(n = 1)
0

Candida spp.
(n = 2)
0

Itraconazole

Fluconazole

Candidemia was associated with a prolonged stay

(more than 15 days) in the ICU in these patients. The
intravenous lines were withdrawn from candidemia
patients; failure to remove catheters has been found to
be associated with poor outcome, which could simply
reflect a high probability of death [13,14]. Another
important factor was prior administration of
antimicrobials leading to impaired gut flora and
impaired gut motility with subsequent overgrowth of
yeast contributing towards candidemia [15,16].
Multiple predisposing and underlying factors were
probably responsible. Frequently, early treatment or
prophylactic intervention with antifungal drugs is
given to reduce the risk for subsequent candidemia in
ICU patients [17]. As with the widespread use of
broad-spectrum antimicrobials, the selective pressure

exerted by the frequent use of antifungals also

encourages the proliferation of drug-resistant Candida
spp. posing a new challenge in the effective
management of nosocomial candidemia [18].
Risk factors that were identified in patients
with non-albicans candidemia were prior use of
antimicrobials and use of central venous catheters,
with both being present more frequently in patients
with non-albicans candidemia than albicans
candidemia (Table 2). All these factors are well known
and the current findings are in concordance with the
reports of previous researchers [19].
This study again focuses attention on nonalbicans Candida isolates being resistant to
fluconazole. This aspect has been highlighted by the
isolation of C. glabrata spp. in five cases out of a total
673

Chander et al. Epidemiology of candidemia

of 27 patients in the study. Resistance to amphotericin

B is attributable to the reduction in ergosterol in
resistant mutants of Candida. Such cases have been
reported from immunocompromised patients who have
received extensive antifungal agents and broadspectrum antimicrobials. The susceptibility data are
similar to those of other studies published in recent
years [20]. Kothari et al. have previously reported
83% of C. tropicalis and 42% of C. albicans to be
resistant to fluconazole [21]. Patients with nonalbicans Candida are more likely to require a greater
dosage of fluconazole to be cured clinically. There is
need, therefore, to identify patients at risk of nonalbicans Candida candidemia to initiate empirical
therapy.
In the ICU, there is usually a failure of host
defense mechanisms and also complications associated
with the patients underlying disease. Therefore,
mortality is not solely related to the pathogenicity of
the Candida species. In this study, mortality in patients
presenting with candidemia was high, but direct
correlation of candidemia and mortality could not be
ascertained. However, in previous publications,
mortality in patients with candidemia has been
reported to be up to 80% [18,19]. Barberino et al.
suggest that invasive candidiasis is a better marker for
disease severity than an independent risk factor for
mortality during the course of infection [22].
Based on the present results, it is clear that routine
screening of Candida isolates to the species level
followed by confirmation of resistant strains by
antifungal susceptibility testing is essential. Clinicians
must be aware of the wide breadth of debilitating
conditions in which candidemia can arise, as removal
of central lines, withdrawal of broad-spectrum
antimicrobials, and treating the underlying diseases are
all important initial steps in the management of
systemic fungal infections. Moreover, continued
surveillance of candidemia is important to document
changes in its epidemiological features and antifungal
susceptibilities.

J Infect Dev Ctries 2013; 7(9):670-675.

3.
4.

5.

6.

7.

8.
9.
10.

11.

12.

13.

14.

15.
16.

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Corresponding author
Dr. Nidhi Singla
Assistant Professor
Department of Microbiology
Government Medical College Hospital
Sector 32, Chandigarh-160030
India
Email: [email protected]

Conflict of interests: No conflict of interests is declared.

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