C H A P T E R 1 1
Antifungal agents
151
F
ungal infections in humans range from conditions
such as the annoying “athlete’s foot” to potentially fatal
systemic infections. An infection caused by a
fungus
is
called a
mycosis
. Fungi differ from bacteria in that the
fungus has a rigid cell wall that is made up of chitin
and various polysaccharides and a cell membrane that
contains
ergosterol
. The composition of the protective
layers of the fungal cell makes the organism resistant to
antibiotics. Conversely, because of their cellular makeup,
bacteria are resistant to antifungal drugs.
The incidence of fungal infections has increased
with the rising number of immunocompromised indi-
viduals—people with acquired immune deficiency
syndrome (AIDS) and AIDS-related complex (ARC),
those taking immunosuppressant drugs, those who have
undergone transplantation surgery or cancer treatment
and members of the increasingly large elderly popula-
tion, whose body is no longer able to protect itself from
the many fungi that are found throughout the environ-
ment (Box 11.1). For example,
Candida
,
a fungus that is
normally found on mucous membranes, can cause yeast
infections or “thrush” in the gastrointestinal (GI) tract
and yeast infections or “vaginitis” in the vagina.
SYSTEMIC ANTIFUNGALS
The drugs used to treat systemic fungal infections
(Table 11.1) can be toxic to the host and are not used
indiscriminately. It is important to get a culture of the
fungus causing the infection to ensure that the right
drug is being used so that the person is not put at addi-
tional risk from the toxic adverse effects associated with
these drugs.
A
zole antifungals
The
azoles
are a large group of antifungals used to treat
systemic and topical fungal infections (Table 11.1). The
azoles include fluconazole (
Canesoral
,
Diflucan, Dizole
),
itraconazole (
Sporanox
), ketoconazole (
Nizoral
), posa-
conazole (
Noxafil
), terbinafine (
Lamisil
,
Tamsil
) and
voriconazole (
Vfend
). Although azoles are considered
less toxic than some other antifungal agents, such as
amphotericin B, they may also be less effective in very
severe and progressive infections.
Therapeutic actions and indications
These drugs bind to sterols and can cause cell death
(a fungicidal effect) or interfere with cell replication
(a fungistatic effect), depending on the type of fungus
being affected and the concentration of the drug. (See
Figure 11.1.)
BOX 11.1
Drug therapy across the lifespan
Antifungal agents
CHILDREN
Children are very sensitive to the effects of most antifungal
drugs and more severe reactions can be expected when
these drugs are used in children.
Many of these drugs do not have proven safety and
efficacy in children and extreme caution should be
exercised when using them. Fluconazole, ketoconazole,
terbinafine and griseofulvin have established paediatric
doses and would be drugs of choice if appropriate for a
particular infection.
Topical agents should not be used over open or
draining areas that would increase the risk of systemic
absorption and toxicity. Occlusive dressings, including
tight nappies, should be avoided over the affected areas.
ADULTS
These drugs can be very toxic to the body, and their use
should be reserved for situations in which the causative
organism has been identified. Over-the-counter topical
preparations are widely used, and people should be
cautioned to follow the instructions and to report
continued problems to their healthcare provider.
PREGNANCY AND BREASTFEEDING
Pregnant and breastfeeding women should not use these
drugs unless the benefit clearly outweighs the potential
risk to the fetus or neonate. Women of childbearing age
should be advised to use barrier contraceptives if any
of these drugs are used. A severe fungal infection may
threaten the life of the mother and/or fetus; in these
situations, the potential risk of treatment should be
carefully explained.
Topical agents should not be used over open or
draining areas, which would increase the risk of systemic
absorption.
OLDER ADULTS
Older people may be more susceptible to the adverse
effects associated with these drugs and should be
monitored closely.
People with hepatic dysfunction are at increased
risk for worsening hepatic problems and toxic effects
of many of these drugs (ketoconazole, itraconazole,
griseofulvin). If hepatic dysfunction is expected (extreme
age, alcohol abuse, use of other hepatotoxic drugs), the
dose may need to be lowered and the person monitored
more frequently.
Other agents are associated with renal toxicity
(flucytosine, fluconazole, griseofulvin) and should be
used cautiously in the presence of renal impairment.
People at risk for renal toxicity should be monitored
carefully.
