The Wadsworth Center of
New York State, Department of Health reported, that members of the genus Candida are found in
all areas of the intestinal tract, usually causing no medical problems.
However, in patients with a compromised immune system, life threatening
diseases may result. In the past two decades Candida species have
become the fifth most common cause of hospital-acquired bloodstream
infections. Advances in immunosuppression for organ transplants and cancer
therapy has increased the susceptible population as has the advent of such
diseases as AIDS which specifically target the immune system. Not only do
these infections result in increased hospital stays, but they have become a
significant cause of mortality in immunocompromised patients.
women produce vaginal secretions with altered levels of glycogen.
This encourages the growth of Candida, and vaginal candidiasis is
common in pregnant women. Their husbands sometimes contract candida
balanitis, a nasty infection of the penis, though this may also be a
consequence of diabetes. If cutaneous candidiasis becomes chronic,
it may be a sign of various abnormalities of the thymus, of the thyroid,
of white blood cells (leucocytes), or be a symptom of AIDS.
Kendrick, The Fifth Kingdom]
The Microbiology and
Immunology Online of University of South Carolina states that
Candida albicans is an endogenous
organism. It can be found in 40-80% of normal human beings. It is present in
the mouth, gut, and vagina. It may be present as a commensal or a pathogenic
organism. Infections with Candida usually occur when a patient has some
alteration in cellular immunity, normal flora or normal physiology. Patients
with decreased cellular immunity have decreased resistance to fungal
infections. Prolonged antibiotic or steroid therapy destroys the balance of
normal flora in the intestine allowing the endogenous Candida to overcome
the host. Invasive procedures, such as cardiac surgery and indwelling
catheters, produce alterations in host physiology and some of these patients
develop Candida infections. Although it most frequently infects the skin and
mucosae, Candida can cause pneumonia, septicemia or endocarditis in the
immuno-compromised patient. The establishment of infection with Candida
species appears to be a property of the host - not the organism. The more
debilitated the host, the more invasive the disease.
colonies of Candida spp. are cream colored to yellowish, grow rapidly
and mature in 3 days. The texture of the colony may be pasty, smooth,
glistening or dry, wrinkled and dull, depending on the species.
The microscopic features of Candida
spp. also show species-related variations. All species produce blastoconidia
singly or in small clusters. Blastoconidia may be round or elongate. Most
species produce pseudohyphae which may be long, branched or curved. True
hyphae and chlamydospores are produced by strains of some Candida spp.
Although they are the members of the
same genus, the various species do have some degree of unique behavior with
respect to their colony texture, microscopic morphology on cornmeal tween 80
agar at 25°C (Dalmau method) and fermentation or assimilation profiles in
* Colony morphology
albicans strains produce white to cream colored, pasty, smooth colonies on
Sabouraud dextrose agar. On phloxine B agar plates, six different colony
phenotypes (smooth, fuzzy, irregular, star, ring, and stipple) are observed.
Significantly, fluconazole MICs of the stipple phenotype were found to be
can best be visualized when the test isolate is incubated on cornmeal tween
80 agar and at 25°C for 72 h. Candida albicans produces clusters of round
blastoconidia along the hyphae and particularly at points of septa.
Pseudohyphae and true hyphae are also observed. Candida albicans, together
dubliniensis, are the two Candida spp. which produce a typical
asexual spore, chlamydoconidium. Chlamydoconidia are round, large,
thick-walled and usually terminal. Candida albicans produces no surface
growth when inoculated in Sabouraud broth.
tube production is the other typical characteristic of this species. Germ
tube is the beginning of true hyphae and observed by microscopic examination
upon inoculation of the strain in serum. Similar to the chlamydoconidia
production, the two Candida spp. that produce germ tube are Candida albicans
and Candida dubliniensis. As will be discussed in the page on Candida
dubliniensis , investigations on simple methods, as well as molecular
studies are on the way to differentiate these two species. In the interim,
in routine laboratory work, a strain that produces germ tube and
chlamydoconidia is defined as Candida albicans.
Candida stellatoidea, once accepted to be a separate Candida species, is now
classified as a subspecies of Candida albicans which differs from Candida
albicans by not assimilating sucrose and not being resistant to
Sabouraud dextrose agar, Candida tropicalis colonies are cream-colored with
a slightly mycelial border. It may produce a thin surface film and bubbles
when grown in Sabouraud broth.
cornmeal tween 80 agar and at 25°C after 72 h, it produces oval
blastospores which are located along the long pseudohyphae. The blastospores
may appear singly or in clusters. The pseudohyphae branch abundantly.
Candida tropicalis may also produce true hyphae
parapsilosis colonies are white, creamy, shiny, and smooth or wrinkled on
Sabouraud dextrose agar. It does not grow on the surface when inoculated
into Sabouraud broth.
cornmeal tween 80 agar and at 25°C after 72 h, it produces blastospores
which are located along the pseudohyphae. Typically, the pseudohyphae may be
curved and large mycelial (hyphal) elements which are called "giant
cells" may be observed.
special precautions other than general laboratory precautions are required.
and other polyenes
NCCLS method is yet insufficient in
discrimination of amphotericin
B-resistant isolates from the susceptible ones, primarily due to the
narrow range of MICs that it generates for all test strains. Modifications
of this method, such as the use of Antibiotic Medium 3 supplemented to 2%
glucose (AM3) instead of the reference RPMI 1640 medium, and use of 24 h
incubation instead of the standard 48 h readings, have yielded inconsistent
results in various investigators' hands. While efforts to develop a novel
relevant methodology for amphotericin B susceptibility testing are in
progress, amphotericin B has proven to be fungicidal against Candida
nystatin appeared active in vitro against some of the isolates with
relatively high amphotericin B MICs.
Azoles and Allylamines
In vitro resistance to azoles is
observed in various Candida spp. While Candida krusei is
intrinsically resistant to fluconazole,
Candida glabrata may be susceptible, dose-dependent susceptible, or
resistant. Other species, such as Candida inconspicua and Candida
tropicalis may also generate high fluconazole MIC. In systemic
infections, fluconazole-resistant Candida albicans isolates are rare
but do exist. On the other hand, patients with AIDS receiving fluconazole
prophylaxis are particularly under risk to develop infections due to
fluconazole-resistant Candida albicans. Genetic mechanisms involved
in multidrug resistance of Candida albicans have recently been
explore. Multidrug efflux pumps have been shown to be involved in
fluconazole resistance in Candida albicans and Candida tropicalis.
Mutation in sterol 14-demethylase P450 enzyme may also lead to azole
The most striking feature of itraconazole
is its favorable in vitro activity against some of the fluconazole-resistant
Candida strains. This property, as well as the availability of its
parenteral formulation, now makes itraconazole a good candidate for
treatment of systemic Candida infections. However, there is
definitely cross-resistance between fluconazole and itraconazole remains
relevant for a subset of Candida isolates, such as some Candida
glabrata strains. Terbinafine,
in combination with fluconazole and itraconazole may also yield enhanced in
vitro activity against some azole-resistant Candida albicans strains.
Candida lipolytica and Candida pelliculosa, on the other hand,
generate high itraconazole MICs in general.
The novel triazoles have favorable in vitro activity against most Candida
spp. Although voriconazole
MICs are relatively high against Candida guilliermondii and Candida
krusei, a recent animal study of therapy of C. krusei infections
suggested good activity. Posaconazole
(SCH56592) MICs in general appear low.
While flucytosine is effective
but now less commonly used against Candida infections, strains which
are primarily resistant to flucytosine or develop resistance during
therapy have been identified.
Synthesis Inhibitors (Echinocandins)
In vitro data obtained so far against Candida
for these novel agents are promising. Agents of this class are active and
often appear fungicidal against both fluconazole-resistant and -susceptible
isolates. Isolates of Candida parapsilosis consistently have elevated
MICs, but the relevance of this is unclear.
Amphotericin B, fluconazole, and
itraconazole in general show favorable activity in vivo in treatment of Candida
infections. Itraconazole alone, as well as itraconazole and flucytosine
combination, proved to have good long term therapeutic efficacy in
esophageal candidiasis in AIDS patients. Importantly and in general,
improvement of unfavorable immune factors constitutes the major issue in
successful clinical outcome of Candida infections. Removal of the
predisposing medical devices, such as catheters or shunts are frequently
required for clinical cure. Nevertheless, failure despite appropriate
therapy with the agent that appears active in vitro, such as amphotericin B
or fluconazole, may be observed. Ketoconazole
is now less commonly used in treatment of Candida infections due to
the availability of more efficacious and less toxic azole compounds.
The echinocandins in development, caspofungin
appear promising in treatment of oropharyngeal and esophageal candidiasis.
Although use of fluconazole might be
beneficial for secondary prophylaxis in patients with AIDS who have
recovered from the primary attack of esophageal candidiasis, the potential
risk of emergence of fluconazole resistance [or appearance of candidiasis
due to fluconazole-resistant species remains. Similarly, fluconazole
prophylaxis following bone marrow transplantation has limited activity
against some non-albicans Candida spp. and no activity against