Introduction to Fungi, Third Edition

CANDIDA (ANAMORPHIC SACCHAROMYCETALES)
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of this organism as a pathogen (Staib et al., 2001;
Bennett & Johnson, 2005).
10.3.3 Treatment of candidiasis and
resistance mechanisms
Candida infections often occur following treatment
with antibacterial antibiotics which also
kill the benign bacteria which compete against
Candida. Such superficial infections are especially
common in mucosal linings of the mouth cavity,
vagina or on the skin. They are collectively called
‘thrush’. Infections of the oesophagus occur in
patients with weakened immune system and are
considered an AIDS-defining illness. The mucous
membranes and skin are usually effective as
primary barriers against infection, and Candida
cells within the human body are vigorously
attacked by the immune system (Murphy, 1996;
Magliani et al., 2005). If all these barriers are
broken or weakened, deep invasive candidiasis
can occur. Yeast cells (conidia) can be disseminated
in the blood stream, and individual organs
can become colonized by hyphae. Contaminated
catheters are also an important entry point
for Candida. An extended account of candidiasis
in all its forms has been given by Kwon-Chung
and Bennett (1992).
Generally, treatment of Candida infections
is difficult because of the relative genetic similarity
between Candida and humans, which
greatly reduces the range of available targets
as compared to the treatment of bacterial
infections. Consequently, certain anti-Candida
drugs have severe side effects. None the less,
drugs belonging to several different classes
are in current clinical use, as reviewed by
Georgopapadakou (1998), Cowen et al. (2002)
and Sanglard and Bille (2002). Lucid accounts of
the fascinating array of mechanisms by which
Candida achieves resistance against the various
drugs are those by Ghannoum and Rice (1999),
Sanglard (2002) and Akins (2005).
Many drugs target ergosterol, a fungal
membrane sterol which is not found in animals.
Amphotericin B (Fig. 10.9a) or nystatin are
polyene antibiotics which associate with ergosterol
in the membranes of Candida, forming
pores in the plasma membrane and thereby rendering
it leaky. Amphotericin B has severe
side effects but has to be used especially against
deep-seated infections (Lemke et al., 2005).
Resistance is usually based on the replacement
of ergosterol by a precursor molecule, or a general
reduction of the sterol content in the plasma
membrane.
Fig10.9 The most important anti-Candida drugs in current use. (a) The polyene compound amphotericin B. (b) The triazole
compound fluconazole. (c) The allylamine terbinafine. (d) The fluoropyrimidine compound 5-fluorocytosine. (e) The echinocandin
caspofungin.