Tsikrikonis Giorgos

Department of Microbiology, Hippokration

General Hospital of Thessaloniki, Greece
Candida infections remain an important cause of
morbidity and mortality in surgical settings.
Surgical patients are at particular risk for fungal
infection: more than 50% of all fungal infections
occur in this patient population.
Data from the NNIS indicated that in the period
from 1989 to 1998 C. albicans was the seventh most
common cause of nosocomial infection in the ICU
setting, accounting for 4.9% of bloodstream
infections and 4.8% of surgical site infections.
Candida species (spp) have emerged as the fourth
most common bloodstream pathogen in the
critically ill with an associated mortality rate of 19-
50%.

Nosocomial Blood Stream Infections, National
Nosocomial Infection Surveilance System (NNIS)
1985-1988
Rank 1988 Pathogen Percent Rank 1984
1 Coag-neg Staph 25.5 1
2 S. aureus 15.0 2
3 Enterococci 7.9 6
4 Candida spp. 7.7 8
5 E. coli 6.8 3
6 Enterobacter 5.2 7
7 P. aeruginosa 5.0 5
8 Klebsiella spp. 4.4 4
Horan T, et al. Antimicrob Newsletter 5:56, 1988
Underlying Conditions Immune
Defects
Iatrogenic Factors
Burns, disruption of
cutaneous or mucosal
barriers
Cancer
Candida colonization
Cytomegalovirus (CMV)
Diabetes mellitus
Graft versus host disease
Hematological malignancies
HIV, DIC, Shock
Malnutrition
Organ transplantation
(liver, pancreas and small
bowel in particular)
Granulocytop
enia
Neutropenia
T-cell
defects
Broad-spectrum
antibiotics
Central venous
catheters
Chemotherapy
High-dose steroids
Immunosuppressive
therapy
Intra-abdominal (GI)
surgery
Total parenteral
nutrition
Longer stays in the
ICU
Risk factors for the development of Candida infections can be broken
down into three components :
The most common types of candida
infections in surgical patients are:
candidemia,
secondary peritonitis
surgical wound infection and
urinary tract infection


Candidemia is the fourth most common
nosocomial bloodstream infection in the United
States. The attributable mortality rate is 33-47%
for invasive Candida infections, which is
significantly higher than the mortality rate for
the other major causes of nosocomial
bloodstream infections.
Central venous catheters are well documented
as independent risk factors for the development
of candidemia. C. albicans and C. parapsilosis
are the most commonly associated Candida spp.
with the production of biofilms on invasive
devices, which renders them nearly completely
resistant to antifungal therapy.

Candida is either the most common or the
second most common pathogen isolated from
the urine in surgical ICU patients. The term
urinary candidiasis refers to an ill-defined
group of syndromes, many of which probably
represent colonization rather than infection.
Candiduria is very common in hospitalized
patients who have urinary catheters in place
for more than 14 days. In this setting it is
more likely to reflect colonization than
infection.
Candidal Endopthalmitis: Usually implies
hematogenous spread to multiple organs.
Identification of eye involvement early in therapy is
crucial for preserving visual activity.
Suppurative thrombophlebitis: Results from
infection of a vessel traumatized by prolonged
catheterization.
Endocarditis: Candida endocarditis is very difficult
to treat. The overall outcome of candida infective
endocarditis is grim, carrying a reported mortality
of up to 80%.
Pericarditis: The surgical patients at risk for
purulent pericarditis caused by Candida are those
who have undergone a cardiac operation, those who
have a malignancy and whose host defenses are
impaired and those who have a debilitating chronic
disease.






Arthritis : Candida joint infections tend to occur in
patients with rheumatoid arthritis or prosthetic joint
devices.
Osteomyelitis: Except for sternal infections
complicating median sternotomy, most cases of
candidal osteomyelitis develop through hematogenous
spread.
Meningitis: Candidal meningitis may follow
hematogenous spread, or it may be a complication of
a neurosurgery or the implantation of
ventriculoperitoneal shunts. The infection is insidious
and sometimes goes undiagnosed. Most patients with
candidal meningitis have recently received
antibacterial agents, and half have previously had
bacterial meningitis.
Pneumonia: True candidal pneumonia is rare, but it
can occur through hematogenous dissemination into
the lung as one of many sites of infection.

Culture: The workup of a surgical patient with
suspected hematogenous candidiasis begins with
a complete set of cultures of sputum,
oropharynx, stool, urine, all drain sites, and
blood.
A rapid and inexpensive test is the germ tube
test (formation of filamentous extensions from
yeast cells in a serum suspension of yeast),
which can distinguish C. albicans (positive result)
from other Candida species.
Positive cultures from nonsterile sites (sputum,
urine, and wound drainage) must be interpreted
with caution because of the frequent occurrence
of Candida as a normal commensal of humans
Histologic analysis: Analysis of fungal smears is a
relatively insensitive method of diagnosing
candidiasis and other fungal infections in
otherwise sterile sites (e.g. joint fluid,
peritoneal fluid, vitreous humor, or
cerebrospinal fluid).
Centrifugation of these fluids and examination
of the sediment may improve the diagnostic
yield.
Conventional fungal stains, such as hematoxylin-
eosin, periodic acid-Sciff (PAS), and Gomori
methenamine-silver (GMS), are useful. The most
sensitive stain is calcofluor white, but
unfortunately it requires fluorescent microscopy.
Deep tissue biopsy provides a definitive diagnosis
of candidiasis.

Candida albicans is the most commonly isolated

Candida spp. Most C. albicans isolates are
sensitive to all of the currently available
agents, but some low-level resistance has been
reported, especially with previous long-term
exposure to azoles at low dosages.

However, the increasing emergence of non-

albicans Candida spp. poses a significant threat
to an older and more immunocompromised
population. Candida glabrata, Candida
tropicalis, and Candida parapsilosis are the
most commonly isolated non-albicans species.
The concern with the increasing number of
Candida non-albicans species is that anti-
fungal susceptibility patterns vary based on
the specific Candida spp.
For example, C. lusitanie may be resistant to
amphotericin B, C. krusei is intrinsically
resistant to fluconazole and C. glabrata
exhibits dose-dependant susceptibility to
fluconazole (i.e., requires higher doses to
effectively treat).
Identifying the specific species of Candida
isolated makes a significant impact on
antifungal therapy decisions.

Species

Polyene

Azole

Echinocandin
Ampho B Flucon Vori Posa Caspo Anid
C. albicans S S S S S S
C. glabrata S to I S-DD to R S - S-DD S - S-DD S S
C. krusei S to I R S - S-DD S - S-DD S S
C. lusitaniae R S S S S S
C. parapsilosis S S S S I I
C. tropicalis S S S to I S S S
Ampho B = amphotericin B, Flucon = filuconazole, Vori = voriconazole,
Posa = posaconazole, Caspo = caspofungin, Anid = anidulafungin. S =
sensitive, S-DD = sensitive dose-dependent, I = intermediate, R = resistant
The following table reflects the susceptibility profiles of the more common
Candida spp.
Our objective was to study the frequency and types
of Candida infections that surgical patients developed
in our hospital over the last three years.
We retrospectively studied all
non-immunosuppressed
patients who underwent
surgery and developed an
infection caused by Candida
species over the last 3 years
in Hippokration General
Hospital of Thessaloniki.
All the samples were
inoculated for culture in
Sabouraud dextrose agar
(SDA) and incubated at 37C
for 24-72 hours.
Germ tube test:
A sample of fungal
spores are suspended in
serum. Incubate the test
at 35
0
C for 2.5-3 hours.
Examine by microscopy
for the detection of any
germ tubes.
Candida albicans was identified by the germ
tube test.
Non-albicans species that were isolated from
blood cultures were identified using the VITEK2
system (bioMrieux).

:
A total of 4279 patients had some type of
postoperative infections, 591 (13.8 %) of
whom developed a Candida infection.

Candida albicans was isolated from 53.5 % of
the infected with Candida patients. Non-
albicans species were detected in 46.5 % of
the positive cultures for Candida.



The site of isolation of Candida isolates was:
67.5 % from urine,
12.7 % from surgical wounds,
10.2 % from blood and
at proportions of 4.5 %, 3.7 % and 1.4 %
from peritoneal fluid, central venous
catheters and other sources respectively.



:
As for candidemias all species isolated were
Candida non-albicans.

Analysis of all positive blood cultures for
Candida yielded detection of:
Candida parapsilosis in 51.4 %,
Candida tropicalis in 21.6 %,
Candida famata in 21.6 % and
Candida glabrata in 5.4 %.



Candida infections represent a significant
proportion of the infections that surgical patients
developed in our hospital (13.8 % of infections
were due to Candida species).
The frequency of isolation of non-albicans strains
was significant (46.5 % of the positive cultures for
Candida).
At ORMC, a review of Candida isolates from blood
and urine cultures from July 2006 through June
2007 revealed a nearly 50:50 split C. albicans to
non-albicans (52% C. albicans, 48% Candida non-
albicans) similar to our study.





Marsch et al, 1983
Few studies have investigated the characterization types
of candida infections in surgical patients.
Compared with the 1980s, a larger proportion of
Candida BSI is now caused by Candida glabrata in
the United States and by Candida parapsilosis and
Candida tropicalis in European, Canadian, and Latin
American hospitals.
This change in the most frequent cause of
candidemia has been explained in part by the high
affinity of C. parapsilosis for intravascular devices
and parenteral nutrition and their widespread use.
The increasing use of antifungal agents to prevent
risk patients might also have favored changes in the
species causing infections. Nosocomial outbreaks of
C. parapsilosis have also been described previously,
and the hands of healthcare workers may be the
predominant environmental source.

Candida has been the commonest fungal pathogen
described in surgical patients in previous studies. An
increasing number of serious Candida infections has
been noted on surgical services in recent years.
This increase may be related to improvements in
surgical technique and perioperative care that allow
high-risk patients to survive, despite serious
underlying diseases. The price for increased survival
is the propensity to develop unusual infections.
The important risk of Candida infections in surgical
patients requires vigilance and probably an early
start of antifungal therapy in patients at high risk.

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